Stud Guideline Document Final

The ASAM/AAAP
CLINICAL PRACTICE GUIDELINE ON THE
Management of
Stimulant Use
Disorder
The ASAM/AAAP
Clinical Practice Guideline on the
Management of Stimulant Use Disorder
Clinical Guideline Committee (CGC) Members (alpha order):

Steven Batki, MD; Daniel Ciccarone, MD, MPH; Scott E. Hadland, MD, MPH; Brian Hurley,
MD (Co-Chair); Kimberly Kabernagel, DO; Frances Levin, MD; James McKay, PhD; Larissa
Mooney, MD (Co-Chair); Siddarth Puri, MD; Richard Rawson, PhD; Andrew Saxon, MD;
Kevin Sevarino, MD, PhD; Kevin Simon, MD; Timothy Wiegand, MD
ASAM Team:
Maureen Boyle, PhD; Amanda Devoto, PhD; Taleen Safarian; Sacha K. Song, MD (medical
editing support)
AAAP Team:
Kathryn Cates-Wessel, Michelle Dirst
IRETA Team:
Dawn Lindsay, PhD; Piper Lincoln, MS; Peter Luongo, PhD
Funding: The development of this Guideline was generously funded with contract support
from the Centers for Disease Control and Prevention (CDC) and the National Institute on
Drug Abuse (NIDA).
ASAM and AAAP are honored that this clinical practice guideline has been endorsed
by:
The American College of Medical Toxicology
The American Society for Adolescent Psychiatry
The American Society of Addiction Nursing
The ASAM/AAAP Clinical Practice Guideline on the Management of Stimulant Use Disorder
TABLE OF CONTENTS
Executive Summary ................................................................................................................. 5
Purpose..................................................................................................................................................................... 5
Background............................................................................................................................................................. 5
Key Takeaways...................................................................................................................................................... 6
Summary of Recommendations ..................................................................................................................... 7
Treatment of Stimulant Use Disorder Recommendations ............................................................ 7
Stimulant Intoxication and Withdrawal Recommendations ..................................................... 18
Secondary and Tertiary Prevention Recommendations ............................................................. 23
Introduction ............................................................................................................................ 28
Purpose.................................................................................................................................................................. 28
Background.......................................................................................................................................................... 28
Scope of Guideline ............................................................................................................................................ 29
Intended Audience............................................................................................................................................ 29
Qualifying Statement ....................................................................................................................................... 29
Methodology ........................................................................................................................... 30
Overview of Approach .................................................................................................................................... 30
GRADE Methodology ................................................................................................................................... 32
Literature Review ............................................................................................................................................. 33
Systematic Reviews and Meta-Analyses............................................................................................. 33
Primary Literature Search ........................................................................................................................ 34
Gray Literature Search ............................................................................................................................... 34
Literature Extraction .................................................................................................................................. 34
Guideline Development .................................................................................................................................. 35
Rating Outcomes ........................................................................................................................................... 36
Rating Quality of Evidence ....................................................................................................................... 36
Developing Evidence to Decision Tables ........................................................................................... 37
Developing Recommendation Statements ........................................................................................ 37
Approving the Recommendations ........................................................................................................ 37
Rating the Strength of Recommendations ......................................................................................... 38
Developing the Guideline Document ................................................................................................... 38
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Engaging Stakeholders ............................................................................................................................... 38

Treatment of Stimulant Use Disorder ............................................................................ 39
Assessment .......................................................................................................................................................... 39
Initial Assessment ........................................................................................................................................ 39
Comprehensive Assessment .................................................................................................................... 40
Behavioral Treatment ..................................................................................................................................... 44
Contingency Management ........................................................................................................................ 44
Community Reinforcement Approach ................................................................................................ 46
Cognitive Behavioral Therapy ................................................................................................................ 47
Matrix Model .................................................................................................................................................. 48
Behavioral Treatment Recommendations ........................................................................................ 48
Technology-Based Interventions .......................................................................................................... 49
Continuing Care............................................................................................................................................. 51
Pharmacotherapy.............................................................................................................................................. 52
Non-Psychostimulant Medications ....................................................................................................... 53
Psychostimulant Medications ................................................................................................................. 59
Co-occurring Disorders .................................................................................................................................. 66
General Guidance.......................................................................................................................................... 67
Concurrent Management of StUD and ADHD ................................................................................... 69
Population-Specific Considerations .......................................................................................................... 72
Adolescents and Young Adults ............................................................................................................... 72
Pregnant and Postpartum Patients ...................................................................................................... 80
Additional Population-Specific Considerations .............................................................................. 84
Stimulant Intoxication and Withdrawal ........................................................................ 89
Assessment and Diagnosis ............................................................................................................................ 90
Initial and Comprehensive Assessment.............................................................................................. 90
Assessment and Diagnosis Recommendations ............................................................................... 96
Setting Determination ..................................................................................................................................... 97
Setting Determination Recommendations ........................................................................................ 98
Managing Stimulant Intoxication and Withdrawal ............................................................................ 99
Stimulant Intoxication ................................................................................................................................ 99
Stimulant Withdrawal .............................................................................................................................. 113
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Monitoring ..................................................................................................................................................... 114

Suicidality ...................................................................................................................................................... 115
Managing Stimulant Intoxication and Withdrawal in Pregnant Patients .......................... 115
Secondary and Tertiary Prevention .............................................................................116
Screening ............................................................................................................................................................ 116
Screening Recommendations................................................................................................................ 117
Assessment ........................................................................................................................................................ 117
Assessment Recommendations............................................................................................................ 119
Early Intervention for Risky Stimulant Use ......................................................................................... 120
Interventions to Reduce Risky Stimulant Use................................................................................ 120
Referral to Treatment for Stimulant Use Disorder ...................................................................... 121
Harm Reduction ............................................................................................................................................... 122
Harm Reduction Education .................................................................................................................... 122
Overdose Prevention and Reversal .................................................................................................... 123
Safer Sexual Practices and Contraception ....................................................................................... 124
Injection Drug Use...................................................................................................................................... 125
HIV Preexposure Prophylaxis ............................................................................................................... 126
Oral Health .................................................................................................................................................... 127
Nutrition ......................................................................................................................................................... 127
Bibliography.......................................................................................................................... 128
Appendix A. Glossary of Terms ....................................................................................... 165
Appendix B. Abbreviations and Acronyms .................................................................168
Appendix C. Differential Diagnosis for Agitation and Psychosis.........................172
Appendix D. Disclosures of Interest.............................................................................. 173
Clinical Guideline Committee Members ................................................................................................ 173
ASAM Quality Improvement Council Members ................................................................................. 175
ASAM Board Members .................................................................................................................................. 177
AAAP Executive Committee ........................................................................................................................ 180
Appendix E. Clinical Questions ....................................................................................... 181
Treatment of Stimulant Use Disorder .................................................................................................... 181
Stimulant Intoxication and Withdrawal................................................................................................ 190
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Secondary and Tertiary Prevention ........................................................................................................ 193

Appendix F. Topics with Insufficient or Negative Evidence .................................197
Appendix G. Additional Resources ................................................................................ 198
Stimulant Use Disorder: General Information and Guidelines .................................................... 198
Other Topics ...................................................................................................................................................... 199
Appendix H. Substance Use Disorder Biopsychosocial Assessment ..................210
Appendix I. Baseline Laboratory Testing .................................................................... 211
Appendix J. Principles of Drug Testing During Withdrawal Management ......212
Appendix K. Psychostimulant Medication Dosing ................................................... 214
Appendix L. Acute Issues and Complications of Stimulant Intoxication and
Withdrawal ............................................................................................................................ 217
Appendix M. Non-acute Issues and Complications of Stimulant Use ................. 220
Appendix N. Medications for Managing Intoxication .............................................. 221
Executive Summary
Purpose
The American Society of Addiction Medicine (ASAM) and the American Academy of
Addiction Psychiatry (AAAP) developed this Clinical Practice Guideline on the Management
of Stimulant Use Disorder (hereafter referred to as the Guideline) to provide evidence-based
strategies and standards of care for the treatment of stimulant use disorders (StUDs),
stimulant intoxication, and stimulant withdrawal, as well as secondary and tertiary
prevention of harms associated with stimulant use.
Background
Rates of StUDs are rising, as are stimulant potency and rates of stimulant use in
combination with opioids. These factors have contributed to overdose death rates
increasing three-fold for cocaine and twelve-fold for other stimulants—including
methamphetamine, amphetamine, and prescription stimulants—in the past ten years.1
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Beyond overdose deaths, StUD can cause a range of serious and long-term health problems,
including cardiac, psychiatric, dental, and nutritional complications. Injection stimulant use
increases the risk of contracting human immunodeficiency virus (HIV), viral hepatitis, and
other infectious diseases such as infective endocarditis. The stable or rising availability of
stimulants, low prices, and potential contamination of stimulants with high potency
synthetic opioids such as fentanyl and other components such as levamisole are expected
to exacerbate risks.
Taken together, these factors have propelled StUD and stimulant use to an urgent health
crisis. This Guideline aims to assist clinicians in treating individuals with StUD (including
adolescents and individuals who are pregnant), as well as individuals experiencing
stimulant intoxication or withdrawal, and individuals who are at high risk of developing
StUD.
Key Takeaways
This Guideline focuses on the identification, diagnosis, treatment, and promotion of
recovery for patients with StUD, stimulant intoxication, and stimulant withdrawal. It also
includes recommendations related to screening for risky stimulant use and secondary and
tertiary prevention of StUD. Recommendations that address general practice for all
substance use disorders (SUDs) are not included, with a few exceptions. The following are
seven key takeaways of this Guideline:
1. Contingency management (CM) has demonstrated the best effectiveness in the
treatment of StUDs compared to any other intervention studied and represents the
current standard of care. CM can be combined with other psychosocial interventions
and behavioral therapies, such as community reinforcement approach (CRA) and
cognitive behavioral therapy (CBT) (See Recommendations 5-6).
2. Pharmacotherapies, including psychostimulant medications, may be utilized off-
label to treat StUD (See Recommendations 9-20).
• When prescribing controlled medications, clinicians should closely monitor
patients and perform regular ongoing assessment of risks and benefits for
each patient.
• Psychostimulant medications should only be prescribed to treat StUD by:
o physician specialists who are board certified in addiction medicine or
addiction psychiatry; and
o physicians with commensurate training, competencies, and capacity
for close patient monitoring.
3. Co-occurring conditions—including but not limited to attention-
deficit/hyperactivity disorder (ADHD), depression, anxiety, eating disorders, and
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other SUDs—are common in patients with StUD. Any co-occurring psychiatric

disorders or SUDs should be treated concurrently alongside StUD with care
coordination (See Recommendations 21-25).
• Evidence supports the use of pharmacotherapy, including psychostimulant
medication, to treat ADHD in individuals with co-occurring StUD.
• Some pharmacotherapies that can be considered to treat StUD off-label have
demonstrated efficacy in treating common co-occurring psychiatric disorders
and SUDs and can be given additional consideration.
4. Clinicians should provide adolescents and young adults who use stimulants with the
same treatment, harm reduction, and recovery support services (RSS) as adults in a
developmentally responsive manner (See the Adolescent and Young Adult Section).
5. Acute stimulant intoxication can result in several life-threatening complications that
include but are not limited to cardiovascular complications (eg, acute coronary
syndrome [ACS], hypertensive emergency, myocardial infarction [MI]),
hyperthermia, and acidosis, among others. These acute issues should be addressed
immediately in an appropriate level of care (See Recommendations 55-72).
6. Treating symptoms of stimulant withdrawal may help supporting ongoing
treatment engagement (See the Stimulant Withdrawal section).
a. Post-acute symptoms of stimulant withdrawal—which include depression,
anxiety, insomnia, and paranoia—can last for weeks to months. It is important to
assess for and treat these symptoms to reduce the risk for decompensation and
return to stimulant use.
7. Secondary and tertiary prevention strategies should be used to reduce harms
related to overdose risk, risky sexual practices, injection drug use, oral health, and
nutrition (See Recommendations 79-92).
Summary of Recommendations
Treatment of Stimulant Use Disorder Recommendations
Assessment Recommendations
Initial Assessment Recommendations
1. When assessing patients for StUD, the first clinical priority should be to identify any
urgent or emergent biomedical or psychiatric signs or symptoms, including acute
intoxication or overdose, and provide appropriate treatment or referrals (Clinical
consensus, Strong Recommendation).
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Comprehensive Assessment Recommendations
2. After first addressing any urgent biomedical or psychiatric signs or symptoms, patients
should undergo a comprehensive assessment that includes:
a. assessment for StUD based on diagnostic criteria (eg, current DSM; Clinical
consensus, Strong Recommendation);
b. a StUD-focused history and physical examination (Clinical consensus, Strong
Recommendation);
c. a mental status exam to identify co-occurring psychiatric conditions, such as
signs and symptoms of psychoses, ADHD, mood disorders, cognitive impairment,
and risk of harm to self or others (Clinical consensus, Strong Recommendation);
and
d. a full biopsychosocial assessment (Clinical consensus, Strong Recommendation).
3. Clinicians treating StUD should conduct routine baseline laboratory testing (Clinical
a. Clinicians should conduct other clinical tests as necessary based on each
patient’s clinical assessment findings (Clinical consensus, Conditional
Recommendation).
4. When evaluating patients with long-term or heavy stimulant use, clinicians should
exercise:
a. an elevated degree of suspicion for cardiac disorders (Clinical consensus,
Conditional Recommendation),
b. a lower threshold for considering ECG testing based on findings of the history
and physical exam (Clinical consensus, Conditional Recommendation),
c. a lower threshold for considering creatine kinase (CK) testing for
rhabdomyolysis based on findings of the history and physical exam (Clinical
consensus, Strong Recommendation), and
d. an elevated degree of suspicion for renal disorders (Clinical consensus,
Conditional Recommendation).
Behavioral Treatment Recommendations
5. Contingency Management (CM) should be a primary component of the treatment plan

in conjunction with other psychosocial treatments for StUD (High certainty, Strong
Recommendation).
6. The following three interventions have the most supportive evidence and are preferred
alongside CM:
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a. Community Reinforcement Approach (CRA) (Low certainty, Conditional

Recommendation),
b. Cognitive Behavioral Therapy (CBT) (Moderate certainty, Strong
Recommendation), and
c. the Matrix Model (Moderate certainty, Conditional Recommendation).
Technology-Based Interventions Recommendations
7. Clinicians can consider offering evidence-based behavioral interventions delivered via

digital therapeutics or web-based platforms as add-on components to treatment for
StUD, but they should not be used as standalone treatment (Low certainty, Strong
Recommendation).
8. Clinicians should consider using telemedicine to deliver behavioral treatment for StUD
to patients who may face challenges accessing in-person care (Moderate certainty,
Strong Recommendation).
Pharmacotherapy Recommendations
Non-Psychostimulant Medication Recommendations
Cocaine Use Disorder: Bupropion Recommendations
9. For patients with cocaine use disorder, clinicians can consider prescribing bupropion to
promote cocaine abstinence (Low certainty, Conditional Recommendation).
a. Clinicians can give bupropion additional consideration for patients with
co-occurring tobacco use disorder (TUD), as this medication can also reduce
nicotine/tobacco use (Low certainty, Conditional Recommendation).
b. Clinicians can give bupropion additional consideration for patients with
co-occurring depressive disorders, as this medication can also treat depression
(Low certainty, Conditional Recommendation).
Cocaine Use Disorder: Topiramate Recommendations
10. For patients with cocaine use disorder, clinicians can consider prescribing topiramate
to reduce cocaine use (Low certainty, Conditional Recommendation).
a. Clinicians can give topiramate additional consideration for patients with
co-occurring alcohol use disorder (AUD), as this medication can also reduce
alcohol consumption (Low certainty, Conditional Recommendation).
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Amphetamine-Type Stimulant Use Disorder: Bupropion Recommendations
11. For patients with amphetamine-type stimulant (ATS) use disorder with low- to
moderate-frequency (ie, less than 18 days per month) stimulant use, clinicians can
consider prescribing bupropion to promote reduced use of ATS (Low certainty,
co-occurring TUD, as this medication can also reduce nicotine/tobacco use (Low
certainty, Conditional Recommendation).
Amphetamine-Type Stimulant Use Disorder: Bupropion and Naltrexone Recommendations
12. For patients with ATS use disorder, clinicians can consider prescribing bupropion in
combination with naltrexone to promote reduced use of ATS (Moderate certainty,
a. Clinicians can give this combination additional consideration for patients with
co-occurring AUD, as naltrexone can also reduce alcohol consumption (Moderate
b. Clinicians can give this combination additional consideration for patients with
co-occurring TUD, as bupropion can also reduce nicotine/tobacco use (Moderate
c. Clinicians can give this combination additional consideration for patients with
co-occurring depressive disorders, as bupropion can also treat depression
(Moderate certainty, Conditional Recommendation).
Amphetamine-Type Stimulant Use Disorder: Topiramate Recommendations
13. For patients with ATS use disorder, clinicians can consider prescribing topiramate to
reduce use of ATS (Low certainty, Conditional Recommendation).
co-occurring AUD, as this medication can also reduce alcohol consumption (Low
Amphetamine-Type Stimulant Use Disorder: Mirtazapine Recommendations
14. For patients with ATS use disorder, clinicians can consider prescribing mirtazapine to
promote reduced use of ATS (Low certainty, Conditional Recommendation).
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a. Clinicians can give mirtazapine additional consideration for patients with

Psychostimulant Medication Recommendations
General Psychostimulant Medication Recommendations
15. Recommendations related to the prescription of psychostimulant medications to treat

StUD are only applicable to:
a. physician specialists who are board certified in addiction medicine or addiction
psychiatry; and
b. physicians with commensurate training, competencies, and capacity for close
patient monitoring (Clinical consensus, Strong Recommendation).
16. When prescribing psychostimulant medications for StUD, clinicians should maintain a
level of monitoring commensurate with the risk profile for the given medication and
patient. Monitoring may include pill counts, drug testing, more frequent clinical contact,
and more frequent prescription drug monitoring program (PDMP) checks (Clinical
Cocaine Use Disorder: Modafinil Recommendations
17. For patients with cocaine use disorder and without co-occurring AUD, clinicians can
consider prescribing modafinil to reduce cocaine use and improve treatment retention
Cocaine Use Disorder: Topiramate and Extended-Release Mixed Amphetamine Salts

Recommendations
18. For patients with cocaine use disorder, clinicians can consider prescribing a
combination of topiramate and MAS-ER to reduce cocaine use and cocaine craving
co-occurring AUD, as topiramate can also reduce alcohol consumption (Moderate
co-occurring ADHD, as MAS-ER can also reduce ADHD symptoms (Moderate
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Cocaine Use Disorder: Amphetamine Formulation Recommendations
19. For patients with cocaine use disorder, clinicians can consider prescribing a long-acting
amphetamine formulation psychostimulant to promote cocaine abstinence (Low
a. Clinicians can give long-acting amphetamine formulation psychostimulants
additional consideration for patients with co-occurring ADHD, as these
medications can also reduce ADHD symptoms (Low certainty, Conditional
Recommendation).
b. When prescribing a long-acting amphetamine formulation psychostimulant,
clinicians can consider dosing at or above the maximum dose approved by the
FDA for the treatment of ADHD to effectively reduce cocaine use (Low certainty,
Amphetamine-Type Stimulant Use Disorder: Methylphenidate Formulations

Recommendations
20. For patients with ATS use disorder, clinicians can consider prescribing a long-acting
MPH formulation to promote reduced use of ATS (Low certainty, Conditional
Recommendation).
a. Clinicians can give long-acting MPH formulations additional consideration for
patients with moderate or higher frequency of ATS use at treatment start (ie, 10
or more days per month; Low certainty, Conditional Recommendation).
b. Clinicians can give long-acting MPH formulations additional consideration for
patients with co-occurring ADHD, as these medications can also reduce ADHD
symptoms (Low certainty, Conditional Recommendation).
c. When prescribing a long-acting MPH formulation, clinicians can consider dosing
at or above the maximum dose approved by the FDA for the treatment of ADHD
to effectively reduce ATS use (Low certainty, Weak Recommendation).
Co-occurring Disorders: General Guidance Recommendations
21. Clinicians should treat both StUD and co-occurring disorder(s) concurrently (Very low
certainty, Strong Recommendation).
22. Clinicians should use an integrated behavioral treatment approach that addresses both
conditions when available (Very low certainty, Strong Recommendation). Otherwise,
clinicians should tailor recommended behavioral therapy for StUD (eg, CM, CBT, CRA)
to address possible interactions between a patient’s StUD and co-occurring disorder(s)
(Very low certainty, Strong Recommendation).
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23. Symptoms of psychosis or mania should be treated with indicated pharmacotherapy

(Moderate certainty, Strong Recommendation).
a. If stimulant-induced psychosis or mania is suspected, clinicians should consider
a gradual taper off antipsychotic medication after a period of remission of
psychotic symptoms (Moderate certainty, Strong Recommendation).
24. When developing a treatment plan for symptoms of depression, anxiety, insomnia,
and/or attentional problems observed during periods of stimulant use or withdrawal,
clinicians should:
a. consider pharmacotherapy based on symptom severity and duration, even if
symptoms are stimulant induced (Very low certainty, Strong Recommendation);
and
b. consider whether the patient’s clinical presentation follows the expected time
course of stimulant-induced symptoms given the phase of use (ie, active use,
waning intoxication, acute withdrawal, post-acute withdrawal, post-withdrawal
abstinence) or are present at other times (Very low certainty, Strong
Recommendation).
25. Clinicians initiating treatment for StUD in a patient with a preexisting co-occurring
diagnosis should:
a. review the patient’s existing treatment plan, ideally in coordination with the
patient’s existing treatment provider(s) (Clinical consensus, Strong
Recommendation); and
b. continue current medications as appropriate (Clinical consensus, Strong
Recommendation), with consideration for safety in the context of the patient’s
potential continued use of stimulants and other substances (Clinical consensus,
Concurrent Management of StUD and ADHD Recommendations
26. For patients with co-occurring StUD and ADHD, clinicians should address ADHD
symptoms as part of the treatment of StUD (Low certainty, Strong Recommendation).
Clinicians should consider:
a. prescribing psychostimulant medications to manage ADHD when the benefits of
the medication outweigh the risks (Low certainty, Strong Recommendation),
b. prescribing non-stimulant medications to manage ADHD when the benefits of
psychostimulant medications do not outweigh the risks (Low certainty, Strong
c. behavioral approaches (Low certainty, Strong Recommendation).
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27. When prescribing psychostimulant medications to a patient with co-occurring StUD and
ADHD, clinicians should consider:
a. using extended-release formulations (Clinical consensus, Strong
b. maintaining a level of monitoring commensurate with the risk profile for the
given medication and patient—monitoring may include pill counts, drug testing,
more frequent clinical contact, and more frequent PDMP checks (Clinical
consensus, Conditional Recommendation).
28. For adolescent and young adult patients with co-occurring StUD and ADHD, clinicians
should additionally consider:
a. arranging for a parent, health professional (eg, trained school nurse), or other
trusted adult to directly observe administration of the medication, especially if
using a short-acting formulation (Clinical consensus, Strong Recommendation);
and
b. counseling families on the importance of safely storing and restricting access to
controlled medications (Clinical consensus, Conditional Recommendation).
Population-Specific Considerations Recommendations
Adolescents and Young Adults Recommendations
Adolescent and Young Adult Assessment and Treatment Planning Recommendations
29. Clinicians should avoid routine drug testing to screen adolescents and young adults for
StUD (Clinical consensus, Strong Recommendation).
a. When considering drug testing in patients under the age of 18, clinicians should
ask patients for permission to test, even if parental/guardian consent was given,
unless obtaining assent is not possible (eg, loss of consciousness; Clinical
30. Clinicians should pay particular attention to signs or symptoms of ADHD and eating
disorders in adolescent and young adult patients (Clinical consensus, Strong
Recommendation).
31. If available, clinicians should refer adolescent and young adult patients to age-specific
treatment and support programs to address identified biopsychosocial needs (Clinical
Adolescent and Young Adult Treatment Recommendations
32. When treating adolescents and young adults for StUD, clinicians should:
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a. consider delivering behavioral interventions that have been demonstrated to be

effective in the treatment of other SUDs in adolescents and young adults (eg, CM,
CBT, CRA, family therapy) and in the treatment of StUDs in adults (eg, CM, CBT,
CRA; Low certainty, Strong Recommendation);
b. use an adolescent- and young adult-specific treatment model (eg, adolescent
CRA [A-CRA]) or tailor existing treatments to be developmentally responsive
(Moderate certainty, Strong Recommendation);
c. use peer-age groups for behavioral treatment in group formats when possible
and avoid incorporating adolescents and young adults into group behavioral
treatment with older adults (Very low certainty, Strong Recommendation);
d. consider treating adolescents and young adults with StUD with the off-label
pharmacotherapies detailed in the Pharmacotherapy section when the
developmentally contextualized benefits outweigh the harms (Very low certainty,
Weak Recommendation);
e. counsel parents/guardians to not conduct home drug tests to assess stimulant
use in adolescents and young adults without the oversight of a trained clinician
(Clinical consensus, Strong Recommendation);
f. recognize that involvement of family members is often beneficial in the
treatment of adolescents and young adults with SUDs and involve family
members and/or trusted adults when appropriate (Clinical consensus, Strong
Recommendation);
g. be familiar with state laws on adolescents’ ability to consent to treatment when
treating minors under age 18; in some states, minors can proceed with
treatment without involvement of a parent or legal guardian in their care,
whereas in other states, parental/guardian consent may be required before
proceeding with some or all aspects of treatment (Clinical consensus, Strong
h. understand that while parental/guardian consent is not required for treatment
of young adults, clinicians should initiate a conversation with the young adult
patient about whether their treatment plan might be enhanced by involving a
trusted adult (Clinical consensus, Strong Recommendation).
Pregnant and Postpartum Patients Recommendations
Pregnant and Postpartum Patients Assessment Recommendations
33. Clinicians should incorporate additional elements into the comprehensive assessment
of StUD for patients who are pregnant, including:
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a. providing referrals to prenatal care providers if not already established (Low

certainty, Strong Recommendation), and
b. reviewing eligibility criteria for locally available programs that specifically
address biopsychosocial needs related to pregnancy and parenting
(eg, childcare, WIC programs; Low certainty, Strong Recommendation).
34. Coordination of prenatal care and treatment of StUD is encouraged (Low certainty,
35. When screening for acute issues, complications, and sequalae associated with stimulant
use in patients who are pregnant, clinicians should pay particular attention to factors
that impact pregnancy and fetal development (Low certainty, Strong Recommendation).
36. Since the ramifications of a positive drug test result for patients who are pregnant may
be more severe than the general populations, before conducting drug testing in patients
who are pregnant, clinicians should:
a. know their state’s requirements on mandatory reporting and ramifications of
reporting (Clinical consensus, Strong Recommendation);
b. weigh the potential benefits with the risks of utilizing drug testing in this
population (Clinical consensus, Strong Recommendation); and
c. obtain informed consent, unless there is immediate clinical need and obtaining
consent is not possible (eg, loss of consciousness; Clinical consensus, Strong
Recommendation).
Pregnant and Postpartum Patients Treatment Recommendations
37. Risk versus benefit to the fetus or infant should be considered when medications are
used to manage StUD, stimulant intoxication, or stimulant withdrawal (Very low
38. Wherever possible, clinicians should incorporate psychosocial treatments targeted
toward meeting the additional needs of patients who are pregnant (Clinical consensus,
Strong Recommendation), including:
a. Parent-focused treatment modalities (eg, parenting skills training; Clinical
b. family-based treatment modalities (Clinical consensus, Strong Recommendation).
39. Clinicians should consider CM to incentivize attendance at prenatal appointments, if
feasible, in addition to usual targets (eg, stimulant abstinence; Low certainty, Strong
Recommendation).
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40. Clinicians should consider providing additional treatment support around the time of
birth, as the postpartum period may be a time of increased stress and risk of return to
stimulant use (Very low certainty, Conditional Recommendation).
Breastfeeding Recommendations
41. Clinicians should educate patients who use stimulants on the risks of use while
breastfeeding and counsel patients not to breastfeed if they are actively using
stimulants (except as prescribed; Very low certainty, Strong Recommendation).
Additional Population-Specific Considerations Recommendations
Sexual Orientation and Gender Identity Recommendations
42. Clinicians should consider referring sexual and gender minoritized (SGM) patients with
StUD to SGM-affirming programs when their history and/or behavior suggest they may
not be comfortable fully participating in a general population setting (eg, distress
related to their identities, difficulties discussing drug-related sexual activities, inner
conflicts, trauma histories) (Low certainty, Strong Recommendation).
Patients Involved in the Criminal and/or Legal Systems Recommendations
43. Initiation of treatment for StUD is recommended for individuals in the criminal and/or
legal systems, including within jails and prisons (Clinical consensus, Strong
Recommendation).
Patients Experiencing Homelessness or Unstable Housing Recommendations
44. For patients experiencing homelessness, housing insecurity, food insecurity, and/or
poverty, clinicians might consider:
a. providing case management services or a referral to a case manager or other
appropriate service provider(s) who can help the patient navigate health and
social safety net resources (Clinical consensus, Strong Recommendation); and
b. providing a referral to a recovery residence based on the patient’s needs
(Clinical consensus, Strong Recommendation).
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Stimulant Intoxication and Withdrawal Recommendations

Assessment and Diagnosis Recommendations
45. The clinical examination should first identify any acute concerns and complications of
stimulant intoxication or withdrawal that would indicate the patient requires a higher
level of care (Clinical consensus, Strong Recommendation). This includes an assessment
of hyperadrenergic symptoms, including tachycardia, hypertension, hyperthermia, and
agitation (Clinical consensus, Strong Recommendation).
46. The initial clinical examination when evaluating for suspected stimulant intoxication or
withdrawal should include (Clinical consensus, Strong Recommendation):
a. a clinical interview (as feasible),
b. physical examination,
c. observation of signs and patient-reported symptoms,
d. review of any available collateral information, and
e. a safety assessment of the patient’s risk of harm to self and others.
47. Stimulant intoxication and withdrawal are primarily diagnosed based on the patient
history and physical examination, as well as findings from any clinical, diagnostic,
and/or toxicology testing (Clinical consensus, Strong Recommendation).
48. If some elements of the medical workup are not available in given a setting, the results
from a basic assessment of vital signs and focused mental status evaluation should be
used to determine the urgency of further medical evaluation or referral for more
comprehensive medical evaluation (Clinical consensus, Strong Recommendation).
49. Clinical testing should be based on presenting signs and symptoms and should include a
complete blood count (CBC), a comprehensive metabolic panel (CMP), LFTs, markers
for muscle breakdown (eg, CK, lactate [in cases of muscle breakdown and acidosis]) or
cardiac injury (eg, CK, troponin; Clinical consensus, Strong Recommendation).
50. When analyzing CBC results for patients with cocaine intoxication or withdrawal,
clinicians should be alert to neutrophil levels, as levamisole is a common adulterant in
the cocaine supply and can cause immunosuppression—in particular, neutropenia—
and small vessel vasculitis (Clinical consensus, Conditional Recommendation).
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Toxicology Testing Recommendations
51. In patients presenting with stimulant intoxication or withdrawal, clinicians can use
toxicology testing to:
a. inform clinical thinking regarding the differential diagnosis, along with other
clinical information (Clinical consensus, Strong Recommendation); and
b. identify substance use that could produce drug–drug interactions when
considering pharmacotherapy to manage signs and symptoms of stimulant
intoxication or withdrawal (Clinical consensus, Conditional Recommendation).
52. Clinicians should consider the possibility of novel psychoactive stimulants if stimulant
intoxication is suspected but presumptive testing is negative (Clinical consensus,
Setting Determination Recommendations
53. Patients with severe clinical concerns or complications related to stimulant intoxication
should be managed in acute care settings (Clinical consensus, Conditional
Recommendation).
54. Some patients with acute stimulant intoxication can be safely managed in lower acuity
clinical settings if (Clinical consensus, Conditional Recommendation):
a. the patient is cooperative with care;
b. the patient is responsive to interventions (eg, verbal and nonverbal
de-escalation strategies, medications) that can be managed in the clinical setting;
c. the patient is not experiencing more than mild hyperadrenergic symptoms or is
responsive to medications that can be managed in the clinical setting; and
d. clinicians are able to:
i. assess for acute issues and complications of stimulant intoxication,
ii. monitor vital signs,
iii. assess and monitor suicidality,
iv. monitor for worsening signs and symptoms of intoxication and emergent
complications related to stimulant intoxication,
v. provide adequate hydration,
vi. provide a low-stimulation environment,
vii. manage the risk of return to stimulant use, and
viii. coordinate clinical testing as indicated.
19
Managing Stimulant Intoxication and Withdrawal Recommendations
Behavioral and Psychiatric Symptoms of Stimulant Intoxication Recommendations
55. Clinicians should evaluate the patient to identify causal factors for agitation and/or
psychosis other than stimulant intoxication; treatment should address all underlying
causes (Clinical consensus, Strong Recommendation).
56. Clinicians should use verbal and nonverbal de-escalation strategies to calm patients
who are agitated, delirious, and/or psychotic to support their cooperation with care
57. Clinicians can consider treating stimulant-induced agitation or confusion with
medication (High certainty, Conditional Recommendation).
a. Benzodiazepines can be considered a first-line treatment for managing
stimulant-induced agitation and/or confusion (High certainty, Conditional
Recommendation).
58. De-escalation strategies should not delay the use of medication to manage patients who
are agitated, delirious, and/or psychotic and at imminent risk for severe complications
(High certainty, Strong Recommendation).
59. Clinicians should treat stimulant-induced psychotic symptoms with an antipsychotic
medication (High certainty, Strong Recommendation).
a. The urgency, formulation, and duration of antipsychotic pharmacotherapy
should be based on etiology and symptomatology (High certainty, Strong
Recommendation).
b. Clinicians should avoid the use of chlorpromazine and clozapine for stimulant-
induced psychosis as these medications may place patients at increased risk for
seizures (High certainty, Strong Recommendation).
60. For agitation and/or psychosis that is moderate to severe or escalating, clinicians
should:
a. conduct a medical evaluation focused on identifying life-threatening medical
signs and symptoms that require referral for emergent hospital workup and
management (Clinical consensus, Strong Recommendation), and
b. conduct a mental status evaluation focused on evaluating the patient’s danger to
self and others that would require immediate referral for full psychiatric
assessment and/or involuntary containment and evaluation (Clinical consensus,
20
61. If agitation and/or psychosis does not respond to the setting’s available de-escalation
and/or medication management interventions, clinicians should coordinate transition
to a more intensive level of care (Clinical consensus, Strong Recommendation).
a. When possible, interventions that address agitation, confusion, delirium and/or
psychosis should be initiated while arranging for transport (Clinical consensus,
62. Clinicians should monitor for progression of psychiatric symptoms, breakthrough
psychosis, suicidality, and emergence of trauma-related symptoms; in particular,
suicidality may increase during waning intoxication and acute withdrawal (Clinical
Hyperadrenergic Symptoms of Stimulant Intoxication Recommendations
63. When patients present with hyperadrenergic symptoms, clinicians should provide
ongoing monitoring and management of vital signs—especially heart rate and blood
pressure—to prevent complications that may result from untreated sympathomimetic
toxicity (Clinical consensus, Strong Recommendation).
64. Clinicians should treat patients in a stimulant-induced hyperadrenergic state with
GABAergic agents (eg, benzodiazepines, phenobarbital, propofol); benzodiazepines can
be considered first-line treatment for this purpose (Low certainty, Strong
Recommendation).
65. If the hyperadrenergic state persists despite appropriate improvement in agitation and
neuromuscular hyperactivity following treatment with benzodiazepines or other
GABAergic agent, clinicians can consider adjunctive treatment with the following
medications:
a. A beta blocker with concomitant alpha-1 antagonism (eg, carvedilol, labetalol;
Moderate certainty, Conditional Recommendation).
b. An alpha-2 adrenergic agonist (eg, dexmedetomidine for severe symptoms,
clonidine for mild to moderate symptoms; Moderate certainty, Conditional
Recommendation).
c. Where beta blockers are contraindicated, clinicians can consider other
pharmacological options such as calcium channel blockers, alpha-1 adrenergic
antagonists, alpha-2 adrenergic agonists, and nitric oxide-mediated vasodilators,
with consideration of other clinically relevant signs and symptoms (Moderate
d. While calcium channel blockers, alpha-1 adrenergic antagonists, alpha-2
adrenergic agonists, and nitric oxide-mediated vasodilators may be most
beneficial in treating hypertension and vasospasm, clinicians should be alert to
21
potential side effects, including poor control over tachycardia or reflex

tachycardia (Moderate certainty, Strong Recommendation).
66. If a patient with stimulant intoxication is experiencing a hypertensive emergency,
clinicians should:
a. use short-acting agents such as sodium nitroprusside, phentolamine, or
dihydropyridine calcium channel blockers (Very low certainty, Strong
Recommendation);
b. avoid long-acting antihypertensives to avoid abrupt hemodynamic collapse
(Very low certainty, Strong Recommendation); and
c. use nitroglycerin if the patient exhibits signs or symptoms of cardiac ischemia
Acute Issues and Complications Recommendations
Chest Pain Recommendations
67. For patients experiencing chest pain during stimulant intoxication, clinicians should
initiate treatment for the underlying intoxication with GABAergic agents
(eg, benzodiazepines, phenobarbital, propofol) as long as there are no clinical
contraindications (Moderate certainty, Conditional Recommendation).
68. Alternative agents (eg, calcium channel blockers, vasodilators) are generally preferred
for management of cardiac ischemia in patients experiencing stimulant intoxication.
However, if beta blockers are used in patients with stimulant intoxication, clinicians
should consider using a medication with concomitant alpha-1 antagonism
(eg, carvedilol, labetalol). If an unopposed beta blocker was used in a patient who is or
was recently stimulant intoxicated, clinicians should also consider providing a coronary
vasodilator (eg, nitroglycerin, calcium channel blocker). For complex cases, consult with
cardiology and/or medical toxicology (Low certainty, Conditional Recommendation).
69. While treating underlying stimulant intoxication in patients experiencing chest pain,
clinicians should concomitantly evaluate for ACS and other causes of acute chest pain in
stimulant intoxication (eg, pulmonary, musculoskeletal [MSK]). Chest pain that does not
fully resolve as signs and symptoms of stimulant intoxication improve should be
evaluated and treated following current standards of care (Moderate certainty, Strong
Recommendation).
QRS Widening Recommendations
70. Cocaine has local anesthetic-like effects at sodium channels and can cause QRS
widening with impairment in cardiac contractility during severe cocaine intoxication. If
22
these issues are identified, in addition to treating intoxication, clinicians should

administer sodium bicarbonate to improve the conduction block and contractility; this
will also improve metabolic acidosis if present (High certainty, Strong
Recommendation).
Seizure Recommendations
71. When a patient presents to the emergency department (ED) with seizures following
stimulant use, full neurological workup is not necessary if the seizures are well
explained by substance use or withdrawal (Clinical consensus, Conditional
Recommendation).
a. When the etiology of the seizures is not well explained by stimulant use, the
workup and management of seizures should proceed according to usual best
practices (Clinical consensus, Strong Recommendation).
72. For stimulant intoxication-related seizures or concomitant alcohol- or sedative-related
seizures, clinicians should treat with benzodiazepines (High certainty, Strong
Recommendation).
a. If seizures are refractory to benzodiazepines, clinicians can consider treating
with either phenobarbital or propofol (High certainty, Strong Recommendation).
Follow-up Recommendations
73. Clinicians should screen patients for StUD and engage them in brief interventions using
motivational interviewing (MI) or motivational enhancement therapy (MET) to
facilitate referral for assessment for StUD, if indicated (Very low certainty, Conditional
Recommendation).
Secondary and Tertiary Prevention Recommendations

Screening Recommendations
74. When general healthcare providers screen adolescents or adults for risky substance use
per USPSTF guidelines,2 they should include screening for stimulant misuse
(ie, nonmedical or nonprescribed use; Very low certainty, Strong Recommendation).
75. Clinicians should consider more frequent screening for stimulant misuse in patients
who take prescribed psychostimulant medications (Very low certainty, Strong
Recommendation).
76. Clinicians should check their state’s PDMP prior to prescribing psychostimulant
medications (Moderate certainty, Strong Recommendation).
23
77. For patients who screen positive for stimulant misuse:

a. Clinicians should conduct a focused history and clinical exam to evaluate
complications of use related to route of administration and type of preparation
used and provide treatment or referrals as appropriate (Very low certainty,
b. Clinicians should assess the following to determine harm reduction service and
counseling needs:
i. risky patterns of stimulant use, including:
1. frequency and amount of use, including binge use (High certainty,
Strong Recommendation);
2. use of stimulants with no one else present (High certainty, Strong
Recommendation);
3. concurrent use of prescribed and nonprescribed medications and
other substances, particularly opioids, alcohol, and other central
nervous system depressants (High certainty, Strong
Recommendation);
4. history of overdose (High certainty, Strong Recommendation); and
5. history of stimulant-related ED visits and hospitalizations (High
certainty, Strong Recommendation);
ii. routes of administration, particularly injection drug use (Very low
certainty, Strong Recommendation); and
iii. risky sexual behaviors (High certainty, Strong Recommendation).
c. Clinicians should consider asking patients about:
i. the context of their stimulant use (eg, chemsex, weight loss, academic or
work performance, staying awake; Clinical consensus, Strong
Recommendation),
ii. trauma (Clinical consensus, Strong Recommendation), and
iii. intimate partner violence (IPV; Clinical consensus, Strong
Recommendation).
d. Clinicians should conduct baseline laboratory testing based on clinical
assessment of risk factors (see Assessment; Clinical consensus, Strong
Recommendation).
24
78. Patients who engage in nonmedical use of prescription stimulants should be evaluated
for ADHD, which may also require treatment (Clinical consensus, Strong
Recommendation).
Early Intervention for Risky Stimulant Use Recommendations
Interventions to Reduce Risky Stimulant Use Recommendations
79. Clinicians should consider providing brief interventions to patients with any risky
stimulant use using MI techniques to encourage patients to reduce or stop their use
80. Clinicians should be aware of some of the unique motivators of stimulant use and be
prepared to discuss and suggest safer alternatives as part of brief interventions for
stimulant use (eg, chemsex, weight loss, academic or work performance, staying awake;
Clinical consensus, Strong Recommendation).
Referral to Treatment for Stimulant Use Disorder Recommendations
81. For patients who screen positive for risky stimulant use, clinicians should conduct or
offer referrals for comprehensive assessment and treatment for potential StUD with
linkage support, including warm handoffs (Very low certainty, Strong Recommendation).
82. For patients who are ambivalent about referrals for StUD assessment or treatment,
clinicians should consider using interventions to enhance motivation for treatment
(eg, MI, MET; Very low certainty, Strong Recommendation).
83. Clinicians should consider the use of peer navigators to link patients to StUD
assessment and treatment (Low certainty, Weak Recommendation).
Harm Reduction Recommendations
Harm Reduction Education Recommendations
84. For patients who engage in risky stimulant use, clinicians should:
a. offer basic harm reduction education about safer stimulant use (Low certainty,
Strong Recommendation),
b. tailor harm reduction education to the patient’s patterns of substance use
(eg, context of use, route of administration, type of preparation; Low certainty,
c. refer to relevant local harm reduction services as indicated based on the
patient’s clinical assessment (Low certainty, Strong Recommendation),
25
d. offer harm reduction education on overdose prevention and reversal (High

e. offer harm reduction education regarding safer sexual practices (High certainty,
Overdose Prevention and Reversal Recommendations
85. For patients who use stimulants from nonmedical sources or are socially engaged with
others who do, clinicians should prescribe or distribute overdose reversal medications
(eg, naloxone) or refer patients to locations where they can obtain these medications in
the community (High certainty, Strong Recommendation).
86. Clinicians should recommend that patients perform comprehensive drug checking,
including using fentanyl test strips, every time they obtain a new batch of stimulants
from nonmedical sources and review the technique for using fentanyl test strips when
permitted by state law (Moderate certainty, Conditional Recommendation).
87. Clinicians should consider referring individuals to local supervised consumption sites
(SCS) when available (Moderate certainty, Strong Recommendation).
Safer Sexual Practices and Contraception Recommendations
88. For patients who engage in risky sexual behaviors, clinicians should:
a. offer or refer for sexually transmitted infection (STI) testing at least every 3 to 6
months or more frequently depending on the individual patient’s risk (Moderate
i. consider providing information about local STI testing services where
patients can obtain free or low-cost testing (Moderate certainty, Strong
Recommendation);
b. consider offering a referral to a local psychosocial sex education program or
harm reduction program that addresses risky sexual behavior for additional or
continuing harm reduction intervention (Low certainty, Strong
c. offer condoms and lubrication or advice about where to obtain them (Clinical
Injection Drug Use Recommendations
89. For patients who inject stimulants, clinicians should:
26
a. provide or refer for harm reduction education on safer injection practices and
include information specific to the patient’s stimulant(s) and preparation(s) of
choice (eg, safer acid pairings for crack cocaine injection; Low certainty, Strong
b. provide or refer for safe injection supplies and harm reduction services
HIV Preexposure Prophylaxis Recommendations
90. Clinicians should offer HIV preexposure prophylaxis (PrEP) to patients who use
stimulants and are at increased risk for HIV, including those who:
a. engage in risky sexual behaviors (High certainty, Strong Recommendation),
b. access postexposure prophylaxis (PEP) regularly (High certainty, Strong
Recommendation), and/or
c. inject drugs (High certainty, Strong Recommendation).
Oral Health Recommendations
91. People who use stimulants are at high risk of dental complications, such as poor
dentition, dental carries, abscesses, and subsequent malnutrition. Clinicians should:
a. encourage patients who use stimulants to maintain good oral hygiene and
receive regular dental care (High certainty, Strong Recommendation), and
b. offer referrals to dental care providers if needed (High certainty, Strong
Recommendation).
Nutrition Recommendations
92. People who use stimulants may experience appetite suppression and go for long
periods without appropriate nutrition, placing them at high risk for nutritional deficits
such as malnutrition, cachexia, and sequalae involving specific vitamin deficiencies.
Clinicians should:
a. inquire about diet, nutrition, and food security (Clinical consensus, Strong
b. encourage patients who use stimulants to eat nutritious food (Clinical consensus,
27
Introduction
Purpose
The American Society of Addiction Medicine (ASAM) and the American Academy of
Addiction Psychiatry (AAAP) jointly developed this Clinical Practice Guideline on the
Management and Treatment of Stimulant Use Disorders (hereafter referred to as the
Guideline) to provide information on evidence-based strategies and clinically informed
standards of care for the treatment of stimulant use disorder (StUD), stimulant
intoxication, and stimulant withdrawal. The Guideline also addresses secondary and
tertiary prevention of harms associated with stimulant use. This document draws on
existing empirical evidence and clinical judgment with the goal of improving the quality of
care for people with StUD.
Background
Overdose deaths involving stimulant drugs—including cocaine, methamphetamine,
amphetamine, and prescription stimulants—have risen precipitously over the past
decade.1 Between 2012 and 2021, the rate of overdose deaths involving cocaine more than
tripled from 1.4 per 100 000 in 2012 to 7.3 in 2021, increasing on average by 21% per
year.1 Over the same period, deaths involving methamphetamine, amphetamine, and
prescription stimulants increased more than 12-fold from 0.8 per 100 000 in 2012 to 10.0
in 2021.1 The precipitous increase in novel and designer drugs (eg, cathinones,
amphetamines) in the market complicates the clinical picture.3
While the rate of cocaine use has been relatively flat, rates of cocaine use disorder,
methamphetamine use, and methamphetamine use disorder are rising.4–7 In addition, there
has been a large increase in the risk from use due to the increasing potency of illicit
stimulants and the increasing use of stimulants in combination with opioids, which can
increase toxicity.8 A growing number of people with opioid use disorder (OUD) are using
stimulants intentionally.9 Others may be unaware that the stimulants they use are
contaminated with fentanyl or other opioids.10
In 2021, 50% of all overdose deaths in the US involved stimulants, * 23% involved cocaine,
and 30% involved psychostimulants (primarily methamphetamine). Beyond the mortality
*Per International Classification of Diseases, 10th Revision (ICD-10) underlying cause-of-death codes for
cocaine and psychostimulants with abuse potential (T40.5 and T43.6, respectively) in CDC WONDER.
28
risk, StUD can also lead to long-term health problems, including cardiac, pulmonary,
psychiatric, dental, nutritional, and dermatologic issues, as well as cognitive impairment.11
Further, injection stimulant use puts people at risk for infectious diseases, including human
immunodeficiency virus (HIV) and viral hepatitis, as well as other infectious complications
such as infective endocarditis.11
The most recent National Drug Threat Assessment from the US Drug Enforcement
Administration (DEA) reported stable or rising availability and potency and low prices for
cocaine and methamphetamine that are expected to exacerbate these trends.8 To address
this urgent issue, ASAM and AAAP convened a committee of experts to jointly develop a
clinical practice guideline (CPG) for the prevention and treatment of StUD.
Scope of Guideline
This Guideline focuses on the management of StUD, including the identification, diagnosis,
treatment, and promotion of recovery for patients with StUD, stimulant intoxication, and
stimulant withdrawal. It also includes recommendations related to screening for risky
stimulant use and secondary and tertiary prevention of StUD. With a few exceptions,
recommendations that address general practices for all substance use disorders (SUDs) are
not included.
A glossary of terms used in the Guideline can be found in Appendix A. A summary of

abbreviations and acronyms can be found in Appendix B.
Intended Audience
The intended audience of this Guideline comprises clinicians—including behavioral health
professionals, physicians, nurse practitioners, physician assistants, nurses, and
pharmacists—who provide treatment for StUD, stimulant intoxication, or stimulant
withdrawal in specialty addiction treatment settings and nonspecialty settings such as
primary care offices, emergency departments (EDs), and hospitals. Some recommendations
only apply to specific settings (eg, EDs, non-acute care settings) as indicated in the section
narrative. The Guideline may also be useful for healthcare administrators, insurers, and
policymakers.
Qualifying Statement
This Guideline is intended to aid clinicians in their clinical decision-making and patient
management. It strives to identify and define clinical decision-making junctures that meet
29
the needs of most patients in most circumstances. Clinical decision-making should consider
the quality and availability of expertise and services in the community wherein care is
provided. The recommendations in this Guideline reflect the consensus of an independent
committee (see Methodology) convened by ASAM and AAAP beginning in March 2021. This
Guideline will be updated regularly as clinical and scientific knowledge advances.
Prescribed courses of treatment described in this Guideline are most effective if the
recommendations are followed as outlined. Because lack of patient understanding and
adherence may adversely affect outcomes, clinicians should make every effort to promote
the patient’s understanding of and adherence to prescribed and recommended treatment
services.
Patients should be informed of the risks, benefits, and alternatives to a particular treatment
and should be active parties to shared decision-making whenever feasible. ASAM and AAAP
recognize that there are challenges to implementation of this Guideline in certain settings,
particularly in relation to the availability of contingency management (CM) and community
reinforcement approaches (CRAs) in various communities and settings. However, this
Guideline aims to set the standard for best clinical practice by providing recommendations
for the appropriate care of all patients with StUD in diverse settings. In circumstances in
which the Guideline is being used as the basis for regulatory or payer decisions, the goal
should be improvement in quality of care. Recommendations in this Guideline do not
supersede any federal or state regulations.
Methodology†
Overview of Approach
ASAM’s Quality Improvement Council (QIC) provided oversight for the development of this
Guideline. The recommendations were developed by the Clinical Guideline Committee
(CGC), which was composed of 14 members: 7 (including 1 chair) appointed by ASAM’s
Board of Directors and 7 (including 1 chair) appointed by AAAP’s Board of Directors. One
member from ASAM (Dr. Rawson) resigned prior to completion of the consensus process,
leaving the CGC with thirteen total members.
Nine subcommittees were formed on Intoxication and Withdrawal, Behavioral Treatment,

Pharmacotherapy, Co-occurring Disorders, Adolescents and Young Adults, Pregnant and
†The methodology used for this Guideline was not based on the ASAM Clinical Practice Guideline Methodology
(published fall 2023).
30
Postpartum Patients, Secondary and Tertiary Prevention, Technology-Based Interventions,

and Other Population-Specific Considerations. CGC members met in biweekly
subcommittee meetings to draft recommendation statements.
The CGC was assisted by a technical team from the Institute for Research, Education and
Training in Addictions (IRETA). IRETA supported the systematic literature review, quality
of evidence rating, development of the Grading of Recommendations Assessment,
Development, and Evaluation (GRADE) evidence profiles and recommendations, and initial
drafting of the Guideline document.
A panel of seven patients was convened with assistance from Faces & Voices of Recovery
(FAVOR) and Young People in Recovery (YPR) to provide feedback to the CGC at various
stages of development, including determining the importance of outcomes to consider
when weighing the harms and benefits of interventions. Unfortunately, the patient panel
was not engaged to the degree initially hoped; only one patient panel member attended the
scheduled meetings. We surmised that the patient panel may have found it intimidating to
interact with professional medical societies. In response, we developed an anonymous
survey to collect input that FAVOR and YPR disseminated to their membership; however,
we received few responses. When the draft Guideline was sent out for public comment, it
was sent to these and other patient advocacy organizations, but no feedback was received.
The CGC recognizes that new strategies are required to effectively engage with patient
stakeholders in this work. ASAM and AAAP will continue to iteratively explore new
strategies for patient engagement in the development of CPGs.
All members of the QIC, Board of Directors, and CGC, as well as external reviewers of the
Guideline, were required to disclose all current relevant relationships with industry and
other entities that may represent actual, potential, or perceived conflict of interest. These
disclosures are summarized in Appendix D. In general, if significant conflicts of interest are
identified, committee members with significant disclosures of interest are asked to recuse
themselves from voting on any relevant recommendation statements that presents a
potential conflict. None of the disclosures from the CGC were deemed to present significant
conflicts of interest in relation to the recommendation statements. Disclosures of interest
for members of ASAM’s QIC and Board of Directors and AAAP’s Executive Committee were
reviewed and no significant conflicts of interest were identified.
Table 1 broadly summarizes the scope and key questions developed by the CGC (see Table
1). More details about PICOS for each clinical question can be found in the EtD tables
supplemental document.
31
Table 1. Management of Stimulant Use Disorder Scope and Key Questions Components
(PICOS)
Population Individuals with StUD (including adolescents and pregnant individuals)

Individuals experiencing stimulant intoxication and/or withdrawal
Individuals at high risk for developing StUD
Interventions Pharmacotherapy for StUD (Non-stimulant medications; stimulant
medications)
Behavioral treatment for StUD (Contingency Management, Cognitive
Behavioral Therapy; Community Reinforcement Approach)
Intoxication and Withdrawal Management approaches
Secondary and Tertiary Prevention strategies
Comparisons Treatment as Usual
Outcomes Stimulant abstinence
Stimulant use reduction
Other substance use
Treatment retention/attrition
Adverse events
Risky behavior reduction
Timing Any timing
Setting Outpatient substance use treatment

Residential substance use treatment
Prenatal clinics
General medical settings
Emergency departments
Hospital
GRADE Methodology
The Guideline was developed using the GRADE Evidence to Decision (EtD) framework for
producing recommendations in health care.12 GRADE provides a systematic, transparent
approach to developing recommendations based on scientific evidence and the clinical
32
judgment of experts. The GRADE process encompasses systematic review of clinical

evidence and its quality, consideration of existing guidelines, expert committee consensus,
stakeholder comment and reconciliation, and document development.
Literature Review
A systematic literature review was conducted to support the GRADE evidence profiles used
as part of the Guideline’s development process. The literature review focused on
identifying high-quality systematic reviews and meta-analyses, as well as new research
published since the completion of those systematic reviews. The first stage of the literature
review focused on locating existing systematic reviews, clinical guidelines, and gray
literature on the management and treatment of StUD. The second stage of the literature
review focused on locating primary research on topics for which moderate- to high-quality
systematic reviews were not available and primary research released since the publication
of high-quality systematic reviews. The third stage of the literature review used targeted
literature searches to identify research on clinical questions identified by the CGC (see
Appendix E). These searches were limited to a ten-year period.
Titles, abstracts, and full texts were reviewed by two independent senior members of the
research team for inclusion in the literature review.
Supplemental literature searches were also conducted at the request of the CGC after
completion of the initial literature review during the recommendation development
process. These searches generally dropped the ten-year restriction, or terms were
broadened to include other substances or populations with mixed SUDs that could be
generalized to patients with StUD. Titles, abstracts, and full texts were reviewed by one
senior member of the research team. CGC members were also permitted to request that a
particular research document be included in an evidence profile.
Systematic Reviews and Meta-Analyses

A search for systematic reviews, clinical guidelines, and meta-analyses was conducted in
the PubMed and PsycInfo literature databases on June 1, 2021. All text fields were
searched, and the search was limited to articles published about humans in the prior ten
years and available in English. Where authors or recommending bodies had published
updates of an analysis or guideline, only the most recent version was included.
33
Primary Literature Search

A primary literature search was conducted in PubMed and PsycInfo on August 11, 2021.
This search aimed to identify original research on topics for which high-quality reviews
were not available and capture literature released after the publication of high-quality
systematic reviews using a title, abstract, and keyword field search. All clinical study
designs with random and nonrandom assignments were included, but case studies were
excluded. If an article reflected a secondary analysis of data from a relevant study, the
original report was included in the literature review.
Gray Literature Search

An internet search for gray literature was conducted during June 2021 that targeted
published and unpublished clinical guidelines related to the management of StUD. The
search followed the process suggested by the National Academy of Medicine (NAM) for
searching gray literature.13 The search was not limited by publication date; however, where
recommending bodies had published updated guidelines, only the most recent versions
were included.
Literature Extraction
Meta-analysis, systematic review, and individual study methods were extracted by one
member of the research team. The quality of the meta-analyses, systematic reviews, and
individual studies identified in the literature review was rated using standardized
assessment scales. Appraisals were conducted by two independent members of the
research team using the AMSTAR-2 tool for systematic reviews and meta-analyses,14 the
revised Cochrane Risk of Bias (RoB 2) tool for randomized trials,15 and the Cochrane Risk of
Bias In Non-randomized Studies – of Interventions (ROBINS-I) tool for nonrandomized
trials.16 A third senior member of the research team reconciled any disagreements in the
appraisals. Evidence identified in the supplemental literature searches conducted during
the recommendation development process at the request of the CGC were not individually
appraised due to time constraints. Research results were summarized in a narrative
literature review.
Existing guidelines on relevant topics were listed in the corresponding EtD table.
Recommendations made in some non-systematic reviews identified in the literature search
but excluded based on publication type were extracted at the request of the CGC when
other existing recommendations could not be found.
34
Guideline Development
Ideally, a CPG is based on scientific evidence that is translated into practical
recommendations for use by clinicians, policymakers, and the public. Recommendations
are meant to inform decision-makers of evidence-based practices and standards of care.
The GRADE approach includes four elements to consider when translating evidence
into recommendations:
1. the balance of benefits and harms of the intervention in question,
2. the certainty of evidence about the benefits and harms,
3. the values and preferences of the populations affected by the guideline, and
4. the acceptability and feasibility of implementing the recommendation.12
Other criteria can also be considered, such as the cost and/or burden of the intervention
and the impact of the recommendation on health equity.
The results of the literature review inform estimates of the size of benefits and harms and
the certainty of the evidence of effects. A survey distributed to the patient panel and the
clinical experience of the CGC informed judgments about patient preferences for different
intervention outcomes. The feasibility of interventions was determined primarily by the
clinical experience of the CGC, as acceptability and feasibility were not targets of the
literature review.
Evaluations of these criteria are reflected in the strength of a recommendation and

phrasing that may make the recommendation conditional (eg, depending on patient values,
resource availability, or setting), discretionary (eg, based on the opinion of the patient or
practitioner), or qualified (eg, by an explanation regarding the issues that would lead to
different decisions).
Strong recommendations support actions in which benefits clearly outweigh harms, or vice
versa, and for which patients have expressed clear and consistent values or preferences.
They generally apply to most patients in most circumstances. Strong recommendations are
typically based on high- or moderate-certainty evidence. A strong recommendation may be
based on low-certainty evidence, for example, when the evidence indicates a substantial
net benefit in a life-threatening situation or when there is limited evidence for a practice
that is considered standard of care.
Moderate or conditional recommendations are often based on lower-certainty evidence

that shows benefits more closely balanced with harms or variability in patient preferences.
They may apply to many but not most patients. Implementation is often determined by
variation in individual clinical situations—including disease factors, patient preferences
and characteristics, and resource use—and usually involves a shared decision-making
process.
35
Recommendations may be made even when there is low-certainty or insufficient evidence.

The evidence base is still accumulating in many areas of addiction treatment, but the
urgency and severity of SUD-related issues demand that clinicians act, even in the face of
imperfect empirical evidence. Recommendations based solely on clinical consensus are
clearly indicated and their rationale explained.
Rating Outcomes
Healthcare decision-making involves balancing multiple potential benefits and harms.
When comparing treatment options that produce different sets of outcomes, it is helpful to
first establish each outcome’s relative importance before evaluating and comparing
options. The literature review generated a list of outcomes measured in clinical research on
StUD-related interventions. The CGC and patient panel independently rated outcomes to
prioritize in terms of their importance to clinical decision-making or patient values,
respectively, via an online survey (with patient panel participation limitations noted in
Overview of Approach). Importance was indicated on a 1-to-9 scale, with an average
below 4 indicating limited importance, 4 to 6 as important but not critical, and greater
than 6 as critically important for decision-making. More important outcomes carried more
weight when comparing interventions with different outcomes.
Rating Quality of Evidence

Evidence from the literature review was organized by intervention and outcome in a
Summary of Findings table for each recommendation. The certainty of the body of evidence
(ie, compiled across evidence types) for each intervention and outcome pair was rated by
one member of the research team as high, moderate, low, or very low based on the
following indicators:
• the quality or risk of bias in the included evidence assessed as part of the literature
review,
• the consistency of findings across the evidence,
• the precision of estimated treatment effects,
• the directness or generalizability of the evidence to the guideline population, and
• the possibility of publication bias.
In situations where no direct or relevant experimental evidence was found related to a
given recommendation, the certainty of evidence was labeled clinical consensus.
36
Developing Evidence to Decision Tables

Following the GRADE framework, the CGC used EtD tables to document the evidence and
decisions made while drafting, deliberating, and finalizing the recommendations. EtD tables
ensure transparency around judgments that result from interpretation of the evidence,
considerations made for different subpopulations, and decisions about how judgments on
different recommendation criteria influence the proposed recommendation. Where
evidence was lacking, the EtD tables identify how the decision to rely on clinical expertise
was made and the clinical perspective and assumptions used to inform judgments in those
areas. EtD tables were formulated around the clinical questions presented in Appendix E.
One committee member initially rated the size of the positive and negative effects of an
intervention, certainty of evidence, patient values and preferences, implementation
feasibility, and other considered elements. Judgments were reviewed and discussed in
subcommittee meetings and revised as appropriate based on the consensus of the
subcommittee and/or CGC. Narrative summaries for each of these judgments were written
by subcommittee members and the research team.
Summaries of findings and EtD tables are available for download as an online supplement.
Developing Recommendation Statements

The recommendation statements were informed by the literature review, EtD tables, and
clinical expertise of the CGC members. This was an iterative process where CGC
subcommittees drafted recommendations, and a review and discussion of the evidence
profile and clinical considerations might have led the CGC to revise the recommendation. In
the absence of relevant evidence, several recommendations were developed based on
clinical consensus.
The CGC addressed evidence deemed negative or inadequate to accurately assess the net
benefit of an intervention overall or in certain patient or intervention subgroups in
Appendix F.
Approving the Recommendations

The CGC voted to approve each recommendation proposed by the subcommittees in a
single round of asynchronous voting. At least 75% agreement among eligible voters was
required to approve a recommendation. If the threshold was not met, the CGC discussed
the recommendation in a virtual meeting with the full committee. The recommendation
could then be approved by voice vote, revised and approved by voice vote, returned to the
37
subcommittee for further amendment (often to revise the supporting EtD table), or
dropped.
Rating the Strength of Recommendations

The CGC voted on the strength of each accepted recommendation as strong, conditional, or
weak based on the overall balance of benefits and harms, the certainty or quality of the
evidence on treatment effects, and patient preferences and values. Strength was indicated
on a 1-to-3 scale; the average was used as the overall strength measure, with less than 1.66
indicating weak, 1.66 to 2.33 indicating conditional, and greater than 2.33 indicating
strong.
Developing the Guideline Document

The Guideline document includes the recommendations approved by the CGC, each with its
recommendation strength rating and evidence quality assessment. Each recommendation
statement is followed by its certainty of evidence rating (high, moderate, low, or very low
certainty) and strength rating (strong, conditional, or weak). Each recommendation is also
accompanied by narrative that describes its rationale and highlights its evidence and
clinical considerations. Additionally, the narrative may describe the CGC’s deliberations to
further inform readers about factors that led to specific recommendation statements.
The narrative also discusses how the Guideline and its recommendations for StUD fit into
the general management of SUD. Rather than duplicate recommendations made in existing
high-quality general SUD guidelines, the CGC attempted to keep the scope of this Guideline
narrowly focused on StUD and how clinical practices differ for this population compared to
other SUDs. However, the CGC did not want the Guideline to be so limited in scope that it
could function only as a supplement. Therefore, good general practices for SUD are
discussed, but any declarative statements made in the narrative are not considered
recommendations within this Guideline. Individuals seeking specific guidance on these
topics should access additional resources; a list of related guidelines and other resources
can be found in Appendix G.
Engaging Stakeholders
The draft Guideline was sent out for public comment in May 2023. ASAM and AAAP invited
their respective Boards, major stakeholders and stakeholder organizations, relevant
committees, and the patient panel to comment. The opportunity to comment was also sent
to all ASAM and AAAP members and made public through ASAM and AAAP websites,
newsletters, and social media.
38
ASAM and AAAP staff collated the public comments, and the CGC analyzed the feedback and
made necessary revisions prior to finalization and publication. Major revisions, including
additional recommendation statements, were subject to a vote by the CGC.
Treatment of Stimulant Use Disorder

Patients with StUD often have co-occurring mental health and biomedical needs. Effective
management may involve interdisciplinary treatment teams that include physicians across
multiple specialties (eg, psychiatry, addiction medicine, medical toxicology), nurses,
behavioral health professionals, nutritionists, and peer support specialists, among others.
Care should be coordinated with appropriate patient consent. Principles of
interdisciplinary care and coordination across the full continuum of care are described in
The ASAM Criteria.17
Assessment
StUD is primarily diagnosed based on the history provided by the patient and a
comprehensive assessment that may include collection of information from collateral
sources, such as family or friends, when available and with patient consent. Subsequent
workup (eg, ordering indicated clinical testing and/or imaging) should be based on the
history and clinical exam findings.
The extent of the clinical exam and medical workup for stimulant intoxication and
withdrawal can be based on presenting signs and symptoms and severity of intoxication or
withdrawal and is discussed in the Stimulant Intoxication and Withdrawal section of this
Guideline.
Initial Assessment
When assessing patients for StUD, the first clinical priority should be to identify any urgent
or emergent biomedical or psychiatric signs or symptoms that may be present and make
appropriate referrals. Identifying urgent or emergent biomedical or psychiatric concerns is
necessary to preserve the health and safety of patients who present for StUD treatment;
acute issues, including signs of acute intoxication or overdose, need to be addressed
immediately.
39
1. When assessing patients for StUD, the first clinical priority should be to identify any
urgent or emergent biomedical or psychiatric signs or symptoms, including acute
intoxication or overdose, and provide appropriate treatment or referrals (Clinical
Comprehensive Assessment
After first addressing any urgent or emergent biomedical or psychiatric signs and
symptoms, patients should receive, or be referred to an addiction treatment provider for, a
comprehensive assessment that includes diagnostic investigation, StUD-focused history
and physical examination, mental status examination, and full biopsychosocial assessment.
Assessment for StUD should be based on accepted criteria, such as that outlined in the
current version of the American Psychiatric Association’s (APA) Diagnostic and Statistical
Manual of Mental Disorders (DSM)—which is the Fifth Edition, Text Revision (DSM-5-TR) at
the time of publication of this Guideline.18 The DSM classifies substance use disorders
(including StUD) as mild, moderate, or severe based on how many of 11 criteria are met:
mild StUD meets 2 to 3 criteria, moderate StUD meets 4 to 5 criteria, and severe StUD
meets 6 or more criteria. Many factors influence the progression of StUD, including the
potency and pharmacokinetics of the stimulants used, frequency of use, route of
administration, and age of first use, among others.19,20
A StUD-focused history and physical examination includes a detailed history of the

patient’s past and current substance use and SUDs and an assessment of non-acute signs
and symptoms of stimulant use, including complications. A mental status exam should
identify concerns such as psychosis, cognitive impairment, and risk of harm to self or
others.
A full biopsychosocial assessment of patients with StUD (or a provisional diagnosis of

StUD) is critical to identify the broad range of biomedical, psychiatric, and psychosocial
challenges that may need to be addressed as part of effective, comprehensive care. Patients’
use of unprescribed stimulants may relate to co-occurring conditions such as eating
disorders, cognitive impairment, or attention-deficit/hyperactivity disorder (ADHD).21–24 If
such issues are identified, the patient should be assessed—or referred for assessment—by
an appropriately qualified clinician (see Co-occurring Disorders).
The biopsychosocial assessment should include age of onset of substance use, family
history of SUD-related issues, ongoing risks related to substance use and SUD-related
behaviors, treatment history and outcomes, psychosocial functioning, and factors in the
patient’s recovery environment that may impact their treatment and recovery support
needs. As with all SUDs, the comprehensive assessment should incorporate social
40
determinants of health (SDOH)—conditions within a person’s home, family, school, and

community that can impact their ability to recover, such as access to safe housing,
economic well-being, exposure to stigma and discrimination, and transportation
challenges, among others.25–29 A summary of the biopsychosocial assessment can be found
in Appendix H.
While comprehensive assessment is vital for each patient’s treatment planning for StUD,
completion of all assessments should not delay or preclude initiation of treatment,
particularly for critical needs (eg, toxicity, psychosis, suicidality, withdrawal). A
comprehensive assessment may be completed over a period of time and may involve
multiple clinicians (eg, social workers, counselors, psychologists, nurses, physicians).
As part of a comprehensive assessment for StUD, clinicians should conduct routine baseline
laboratory testing (see Laboratory Testing). While no research was identified on ordering
routine or as-needed laboratory testing in patients presenting for StUD treatment, the
higher prevalence of HIV, viral hepatitis, and sexually transmitted infections (STIs) in
patients with StUD justifies baseline testing in this population. ‡ Clinicians should consider
all sites of sexual exposure—including urogenital, pharyngeal, and rectal—when testing for
chlamydia and gonorrhea. As with all patients with SUDs, clinicians should assess each
patient’s risks related to sexual practices and consider the need for preexposure
prophylaxis (PrEP) and/or safer sexual practice counseling.
Despite the lack of direct evidence, non-infectious disease screening labs (eg, complete
blood count [CBC], comprehensive metabolic panel [CMP]) can help identify comorbidities
as part of a comprehensive assessment. In addition to baseline labs and in alignment with
recommendations from the Centers for Disease Control and Prevention (CDC), the CGC
recommended that vaccines for hepatitis A virus (HAV) and hepatitis B virus (HBV) be
offered to all patients who are not already immune.31,32 See Appendix I for more
information about routine baseline laboratory testing.
As with any SUD-focused assessment, toxicology and drug testing may be provided as part
of the comprehensive assessment for StUD. The CGC noted the inherent limitations of drug
testing but agreed that testing could be utilized when the outcome would impact clinical
decision-making or be important for medication monitoring or psychiatric follow-up.
Clinicians should consider the technical limitations of the selected matrix and drug panel.
Clinicians should also be aware of which substances are present in the local market and
consider that in testing; for example, testing for fentanyl due to frequent presence in the
stimulant drug supply. If stimulant use is suspected but presumptive testing is negative,
clinicians should consider either confirmatory testing for a strongly suspected substance or
‡ See recommendations compiled by the CDC for infectious disease screening.30
41
the possibility of novel or designer psychoactive stimulants. The CGC noted that tests for
novel or designer stimulants are often expensive with limited availability. Consultation
with laboratory personnel may be helpful when selecting the panel or interpreting results.
For additional considerations, see ASAM’s Appropriate Use of Drug Testing in Clinical
Addiction Medicine consensus statement (major principles of this document are outlined in
Appendix J) and ASAM’s public policy statement on Ethical Use of Drug Testing in the
Practice of Addiction Medicine.33,34
The CGC agreed that clinicians should have an elevated degree of suspicion for
cardiovascular disease when evaluating patients with long-term or heavy stimulant use.
Clinicians should have a lower threshold for conducting cardiac evaluation based on
patient history and physical exam results. At this time, the CGC does not recommend that
all patients with long-term or heavy stimulant use receive an electrocardiogram (ECG).
Clinical management of long-term or heavy stimulant use as it relates to cardiac injury
remains individualized, with strong clinical suspicion of cardiac injury guiding screening,
diagnostics, and treatment.
There is insufficient evidence to recommend routine screening for rhabdomyolysis or renal

disease among patients who use stimulants. However, clinicians should have an elevated
degree of suspicion for these conditions when evaluating patients with long-term or heavy
stimulant use. Consider ordering relevant tests—such as creatine kinase [CK] for
rhabdomyolysis, blood urea nitrogen [BUN]/creatinine ratio [BCR], urine albumin
(ie, proteinuria) for renal disease—at a lower threshold of suspicion based on patient
history and physical exam findings.
If concerns are identified during the assessment, clinicians should either treat or refer the
patient to an appropriate biomedical or psychiatric provider or setting for care. If signs or
symptoms of infection are identified, clinicians should provide treatment or referrals as
appropriate (eg, STI clinic, HIV clinic). Education on and referrals for harm reduction
services (eg, syringe service programs [SSPs]) should also be considered. Clinicians should
work with the patient to develop strategies to address barriers to accessing care that were
identified during the assessment (eg, childcare or transportation support, telehealth).
2. After first addressing any urgent biomedical or psychiatric signs or symptoms, patients
should undergo a comprehensive assessment that includes:
a. assessment for StUD based on diagnostic criteria (eg, current DSM; Clinical
consensus, Strong Recommendation);
42
b. a StUD-focused history and physical examination (Clinical consensus, Strong

Recommendation);
c. a mental status exam to identify co-occurring psychiatric conditions, such as
signs and symptoms of psychoses, ADHD, mood disorders, cognitive impairment,
and risk of harm to self or others (Clinical consensus, Strong Recommendation);
and
d. a full biopsychosocial assessment (Clinical consensus, Strong Recommendation).
3. Clinicians treating StUD should conduct routine baseline laboratory testing (Clinical
a. Clinicians should conduct other clinical tests as necessary based on each
patient’s clinical assessment findings (Clinical consensus, Conditional
Recommendation).
4. When evaluating patients with long-term or heavy stimulant use, clinicians should
exercise:
a. an elevated degree of suspicion for cardiac disorders (Clinical consensus,
Conditional Recommendation),
b. a lower threshold for considering ECG testing based on findings of the history
and physical exam (Clinical consensus, Conditional Recommendation),
c. a lower threshold for considering CK testing for rhabdomyolysis based on
findings of the history and physical exam (Clinical consensus, Strong
d. an elevated degree of suspicion for renal disorders (Clinical consensus,
43
Behavioral Treatment
Contingency Management
Contingency management (CM) is an evidence-based
psychosocial intervention in which patients are given
tangible rewards to reinforce positive behaviors related
Contingency management
to treatment participation or outcomes; vouchers,
(CM) has demonstrated the
prizes, and access to employment have been used
best effectiveness in the
successfully as incentives.35–37 Decades of research
treatment of stimulant use
support the effectiveness of CM at reinforcing
disorders (StUDs) compared to
behaviors—such as abstinence from substances,
any other intervention studied
treatment attendance, and medication adherence—
and represents the current
across different SUDs, including opioid, stimulant,
standard of care.
tobacco, and alcohol use disorder.38–41 CM can also be
combined with other psychosocial interventions, such
as community reinforcement and cognitive behavioral
therapy (CBT).42
There is strong evidence that CM is an effective intervention for increasing treatment

engagement and reducing stimulant use. A systematic review that evaluated reviews
covering various psychosocial and pharmacological interventions for StUD found that CM
was the only efficacious intervention.43 Multiple systematic reviews have shown positive
effects of CM on methamphetamine use,44,45 and one showed effectiveness in reducing
cocaine use in adults.46 CM has demonstrated the best effectiveness in the treatment of
StUDs compared to any other intervention studied and represents the current standard of
care.
Implementation Considerations
Despite its effectiveness, CM is not widely implemented; less than 10% of addiction
treatment programs utilize CM.47 Barriers to implementing CM include regulatory
obstacles, financial costs, stakeholder buy-in, and program resources. These barriers, along
with implementation and dissemination strategies, are well described elsewhere; the
following serves as a general overview alongside CGC comments.48–51 The CGC noted that
while available research suggests CM alone is effective at promoting desired behaviors,
patients with greater or more complex therapeutic needs are likely to benefit from
additional behavioral interventions.
44
Regulatory Barriers
Treatment providers must be mindful of the federal Anti-Kickback Statute, which prohibits
remuneration of patient referrals or generation of business involving medical services
billed to the federal government.52 Concern regarding interpretation of this statute has
been a significant policy barrier to the use of CM. In December 2020, the Office of the
Inspector General (OIG) published clarification—known as the “OIG Final Rule”—that CM
interventions, while not a “safe harbor” (ie, practices not considered kickbacks), are not
inherently in violation of the Anti-Kickback Statute and can be analyzed on a case-by-case
basis.53 However, implementation of CM in compliance with the OIG Final Rule is not well
defined; programs can seek guidance from the OIG but are not required to do so. A recent
report by the Motivational Incentives Policy Group—a stakeholder coalition of CM experts
in policy, research, and legal analysis—outlines “guardrails” that serve as unofficial
guidelines for the use of CM incentives in alignment with the OIG Final Rule.48
Financial Costs
A commonly reported barrier to implementing CM is financial cost. A consistent funding

source—typically government funding or payer reimbursement—is needed to support
implementation. Fortunately, this is beginning to occur; Montana, Washington, and
California have all begun state-funded pilot programs that implement CM.48 Additionally,
some payers have begun reimbursing select CM programs.51
Stakeholder Buy-in
Anecdotally, the CGC noted that resistance to the use of CM for the treatment of SUDs has
been rapidly declining as information about its effectiveness is more broadly disseminated;
however, resistance remains among some stakeholders. The CGC agreed that they would
expect key stakeholders to accept CM, especially when presented with evidence of its
effectiveness.
Clinicians and other staff may initially resist adopting CM due to misconceptions that CM is
rewarding people for substance use and, thus, inappropriate.48,54 However, these attitudes
can be changed through training and exposure.55–57
CM is also gaining support at the federal level. On April 1, 2021, the federal government
issued a statement on drug policy priorities, including goals to “identify and address policy
barriers related to contingency management interventions (motivational incentives) for
stimulant use disorder” and “explore reimbursement for motivational incentives and
digital treatment for addiction, especially stimulant use disorder.”58 Addressing these
priorities would reduce regulatory and financial barriers and facilitate adoption of CM.
45
Program Resources
CM interventions require programs to develop protocols around its use and dedicate
resources, including staff training and time, toward its implementation. Some published
protocols exist for voucher- and prize-based interventions,59,60 as well as some
introductory trainings. § Effective CM interventions are attentive to the schedule,
magnitude, timing, and type of reinforcement; this can be cumbersome in busy treatment
settings, but technology may ease the burden (see Technology-Based Interventions).
Effective implementation of CM requires availability of several components, including

funding, training, capacity for drug testing, and—typically—at least twice weekly clinical
engagement. The CGC emphasized that clinically effective monetary value as contingency
rewards are necessary, though this may be limited by regulations and/or payer policies.
Using an incentive value that is too low does not represent evidence-based practices
and is unlikely to be effective; such implementations may lead decision-makers to
erroneously conclude that CM is not effective.51
Another consideration when implementing CM is the sensitivity of the immunoassay drug

test. It is possible for a drug test to produce a false positive. Clinicians may need to send for
confirmatory laboratory testing, and such a delay could decrease the effectiveness of the
incentives. If other medications prevent the use of CM to promote abstinence from
substances, CM could instead be used to reinforce treatment attendance or other behaviors
related to successful treatment; however, this is less effective.61
Community Reinforcement Approach

Community reinforcement approach (CRA) is a comprehensive behavioral therapy based
on operant conditioning theory.62 Clinicians work closely with patients to adjust aspects of
their lives that interfere with a healthy lifestyle, seeking to build a new way of living
without substances that is more rewarding than their life with substance use.62,63
Moderate evidence exists that suggests CRA is effective for achieving and sustaining
abstinence in patients with cocaine use disorders. Compared to other behavioral
treatments, CRA achieves somewhat better outcomes of abstinence duration, abstinence
rates, and treatment retention among patients with cocaine use disorder, particularly with
longer duration of treatment.42,64
§For example, through the Addiction Technology Transfer Center Network (ATTC) at
https://attcnetwork.org/centers/northwest-attc/cm.
46
For cocaine use disorder, the certainty of the evidence was judged to be modest given that
CRA did not outperform other treatments in all studies.42,64 However, the quality of the
evidence favoring CRA is high, coming from well-conducted randomized controlled trials
(RCTs).
All the reviewed evidence for CRA was based on participants with cocaine use disorder.
The CGC emphasized that no evidence was found for using CRA alone in patients who use
amphetamine-type stimulants (ATS) or methamphetamine. However, the CGC agreed that
there is reason to believe that CRA would be similarly effective with patients who use ATS
as it is with those who use cocaine. CRA by definition needs to be tailored to contextual
factors in the patient’s environment, so any differences in behavioral or environmental
concomitants of the substance being used should be addressed by the intervention.65
CRA combined with CM appears to be effective for reduced stimulant use and treatment
retention. A meta-analysis that analyzed 50 clinical studies on 12 different psychosocial
interventions found that CM combined with CRA was the most efficacious treatment for
StUD, especially cocaine use disorder.42 The CGC concluded that CRA is associated with
apparent benefits and no known undesirable effects.
While CRA appears to be one of the more promising behavioral interventions for StUD,
especially when combined with CM, it has not been widely implemented outside of
research settings.66 Substantial barriers have limited implementation of CRA; it requires a
great deal of resources and patient commitment relative to other behavioral
interventions.66 Few settings have workforces that are appropriately trained to deliver
CRA, and few experts are available to train clinicians in its delivery.66 CRA is costly and
labor intensive; funding and staff levels would have to be increased for adequate
implementation.66
Cognitive Behavioral Therapy

CBT is a type of psychotherapy—delivered by clinicians trained in its use—in which
negative patterns of thought about the self and the world are challenged and skills to cope
with high-risk situations are developed to alter unwanted behavior patterns and treat SUDs
and psychiatric disorders.67–69 Some evidence supports CBT as superior to usual treatment
options, such as individual and group counseling, on stimulant use and abstinence
outcomes during treatment and at follow-up, as well as for treatment retention.42,64
However, CBT has not been found to be superior to usual treatment options for longest
duration of continuous stimulant abstinence or stimulant use at study endpoint.42,70
CBT is a widely utilized and accepted treatment modality. CBT does require resources—
namely, the availability of highly trained clinicians for proper delivery. On the other hand,
47
CBT can be delivered in group sessions, which makes it more feasible for many programs
compared to other behavioral interventions.
Clinicians should be trained in CBT delivery to promote fidelity. The CGC suggested using
an evidence-based CBT manual, such as Project MATCH’s Cognitive-Behavioral Coping Skills
Therapy Manual; the National Institute on Drug Abuse’s (NIDA) Therapy Manual for Drug
Addiction, A Cognitive-Behavioral Approach: Treating Cocaine Addiction; or the US
Department of Veterans Affairs’ (VA) CBT-SUD Among Veterans: Therapist Manual.68,69,71
Matrix Model
The Matrix Model of addiction treatment is a structured, multicomponent behavioral
therapy that delivers individual counseling; CBT, family education, and social support
groups; and encouragement for mutual support group participation over 16 weeks.72
Moderate evidence supports use of the Matrix Model for treatment of StUD. Studies have
demonstrated that the Matrix Model produced greater reductions in methamphetamine
use compared to standard treatment or a wait-list control group.73–75 The Matrix Model
also reduced craving and risky behavior compared to a wait-list control.45
With respect to implementation, the Matrix Model is compatible with the structure and
staffing at many SUD treatment programs and has been widely adopted, demonstrating
feasibility. Programs should assess staffing needs and their network of providers prior to
implementation. As with any new intervention, staff training is an important consideration.
The CGC underscored the superiority of CM as a primary component of treatment for StUD.
Where CM is not available, several other behavioral interventions—notably, CRA, CBT, and
the Matrix Model—should be considered as other effective treatment options.
Behavioral Treatment Recommendations

5. Contingency Management (CM) should be a primary component of the treatment plan
in conjunction with other psychosocial treatments for StUD (High certainty, Strong
Recommendation).
6. The following three interventions have the most supportive evidence and are preferred
alongside CM:
a. Community Reinforcement Approach (CRA) (Low certainty, Conditional
Recommendation),
b. Cognitive Behavioral Therapy (CBT) (Moderate certainty, Strong
48
c. The Matrix Model (Moderate certainty, Conditional Recommendation).
Please see the supplementary EtD document for the following related summaries of
evidence, relevant citations, and CGC judgments:
• Table 1. Contingency Management
• Table 2. Community Reinforcement Approach
• Table 3. Cognitive Behavioral Therapy
• Table 4. Matrix Model
Technology-Based Interventions
Technology-based interventions—such as computer, web, or mobile applications—can be
used to implement evidence-based interventions (EBIs) for SUD, such as CBT and CM.76,77
These applications allow for standardized implementation, reduced staff burden, and
increased access to care.76,77
A number of CBT-focused web applications have been developed to deliver SUD treatment,
such as Snow Control for cocaine use disorder, Breaking the Ice for ATS use disorder, and
Computer Based Training for CBT (CBT4CBT) for SUD.76,78–81 The Therapeutic Education
System (TES), an interactive web-based program based on CRA, also contains a CBT
component.82
CBT4CBT can be combined with weekly monitoring check-ins80,81; studies have found
significant reductions in substance use and improved retention in treatment using
CBT4CBT relative to in-person CBT.81,83 In addition to supporting outpatient programs,
evidence suggests that patients in residential treatment programs can also benefit from
web-based CBT interventions.84 A few individual studies across technology-based
interventions reported reduced substance use, particularly in patients who use
cocaine.81,82,85–87 The literature revealed less evidence of efficacy for ATS and
methamphetamine use.
CBT4CBT and TES appear to improve stimulant use outcomes when added to other
behavioral interventions; however, these effects are not always durable.82,83 Some evidence
suggested that these interventions may be similarly effective to clinician delivered
treatment, including CBT. One study suggested the positive effect of TES was greater in
those with a drug positive urine test at baseline.82 While evidence is strongest for cocaine
use, the CGC has no reason to believe the effectiveness would be significantly different for
ATS use.
CM interventions have used webcams and mobile applications to promote cessation of

nicotine/tobacco, alcohol, and illicit drug use.51,88 One model to digitally implement CM is
49
through smartphone–smartcard platforms, where a smartphone application allows for

remote salivary and breathalyzer drug testing at individualized random schedules. The
application tracks the individual’s history of drug tests and treatment attendance and
provides appointment reminders. Incentives are delivered via an anonymous credit card
that cannot be used to withdraw cash and has additional purchasing protections. Studies
show preliminary effectiveness of this model in patients with OUD, including one with
patients who have concurrent StUD.89–91
The CGC reviewed available evidence for a number of technology-based and alternative
interventions but found it to be insufficient to include in the recommendation statements at
this time. These items can be found in Appendix F: Topics with Insufficient or Negative
Evidence.
The CGC expressed concern over the use of standalone technology-delivered interventions.
CBT4CBT has been shown to be effective as a standalone treatment in a few studies, but
this is insufficient evidence to recommend it as a standalone treatment.81,83,92 While some
patients may opt for this approach because they favor the convenience, many will require
more intensive treatment. Additionally, the lack of clinician interactions could make it more
difficult to identify signs of decompensation, such as suicidal ideation or behavior. Patients
who do not have ready access to a computer and the internet and/or who have low
computer literacy could find these interventions difficult to access, disproportionately
impacting patients with lower socioeconomic status.93 Clinicians should be aware that the
Affordable Care Act covers access to phone and internet services for those in need, as well
as training and assistance with computer and phone literacy. Finally, the CGC noted that
text messaging interventions for StUD are promising as add-on interventions; however,
there is insufficient evidence to recommend them at this time.
Another point of caution is that little regulatory oversight currently exists for many of these
technology-based tools. Most digital technologies have little to no evidence of effectiveness;
existing evidence may be low quality or those conducting the studies may have conflicts of
interest. Clinicians should independently evaluate digital technologies for quality before
integrating them into patient care. The APA’s App Advisor can be used to assess mobile
applications; the tool provides reviews by APA members using the App Advisor assessment
framework.94
Telemedicine
Current evidence for the use of telemedicine in the treatment of StUD primarily involves
telephone-based (ie, audio only) interventions, which are often provided after some
amount of in-person care.95–97 The evidence for telephone-based follow-up care of
50
individuals with cocaine use disorder is mixed.96–100 One RCT of a mixed population of
patients with cocaine and methamphetamine use disorders found positive effects on
reduced substance use, suggesting that telemedicine may be effective in the treatment of
methamphetamine use disorder.95 The research base regarding telemedicine is expected to
expand rapidly as a result of increased use during and following the COVID-19 pandemic.
Available resources for utilizing telemedicine include those developed by the Substance
Abuse and Mental Health Services Administration (SAMHSA) and the National Council for
Mental Wellbeing.101,102
While video-based telemedicine has not been studied in this population, the CGC noted that
it is reasonable to think that it would perform similarly to audio-only telemedicine. There
may be acceptability issues due to patients being uncomfortable appearing on camera.
However, with the patient on camera, the clinician may be better able to detect signs of
substance use and/or distress. Telemedicine is also an important tool for expanding access
to care, particularly in rural and underserved areas where SUD treatment services are
limited.
Technology-Based Interventions Recommendations
7. Clinicians can consider offering evidence-based behavioral interventions delivered via

digital therapeutics or web-based platforms as add-on components to treatment for
StUD, but they should not be used as standalone treatment (Low certainty, Strong
Recommendation).
8. Clinicians should consider using telemedicine to deliver behavioral treatment for StUD
to patients who may face challenges accessing in-person care (Moderate certainty,
• Table 5. Computer-Delivered Treatment
• Table 6. Telehealth
Continuing Care
Research has demonstrated that patients with StUD who have not achieved their treatment
goals during the initial phase of treatment may benefit from extended treatment with EBIs
to facilitate long-term recovery.95,99,103,104 CM should be provided to support continuing
care for patients with StUD as they transition through the phases of treatment. Patients
with StUD who are not progressing as hoped toward achieving their goals in an initial
phase of treatment may benefit from extended treatment with EBIs to facilitate long-term
51
recovery.95,99,103,104 Addiction is a chronic illness best addressed with a chronic care model
of disease management. As described in The ASAM Criteria, patients should remain engaged
in the continuum of care; patients who achieve sustained remission (as defined in the
current edition of the DSM) should receive ongoing recovery management checkups to
support rapid reengagement in care in the event of recurrence.17 Clinicians can consider
the use of telemedicine to deliver continuing care.
Pharmacotherapy
No pharmacotherapies have been approved by the US Food and Drug Administration (FDA)
for the treatment of StUD. The following sections discuss considerations for when
pharmacotherapies may be prescribed off-label. The CGC recognized that some clinicians
may be reluctant to prescribe medications off-label. The CGC acknowledged that the
existing evidence for treating StUD with medications is relatively low quality. Despite the
limitations of the evidence, the CGC agreed that medications may be helpful for some
patients with StUD, particularly in the context of certain co-occurring disorders (see
Co-occurring Disorders). The CGC reviewed available evidence related to several
medications that are not included in the recommendations in this section due to negative
or insufficient evidence. These items can be found in Appendix F: Topics with Insufficient
or Negative Evidence.
The pharmacotherapy recommendations in this Guideline discuss both

non-psychostimulant and psychostimulant medications. The CGC emphasized the
importance of careful and ongoing risk–benefit assessments and close monitoring when
prescribing medications for StUD. Clinicians should monitor patient symptoms and
functional status regularly in response to all pharmacotherapies, with increased
monitoring when using medications with higher risk profiles, such as psychostimulants.
Clinicians should monitor medication adherence and nonmedical use through strategies
such as frequent clinical contact, drug testing, pill counts, and prescription drug monitoring
program (PDMP) checks.
The recommendations for non-psychostimulant and psychostimulant medications have

been categorized by substance type (ie, cocaine use disorder and ATS use disorder) due to
their different pharmacological mechanisms of action, which may impact the effectiveness
of pharmacotherapies. Cocaine and ATS both increase dopamine signaling in the brain105;
cocaine blocks the reuptake of dopamine, whereas methamphetamine both increases
dopamine release and blocks its reuptake, resulting in much higher concentrations.105 In
addition, methamphetamine’s half-life of 10 to 12 hours is significantly longer than
cocaine’s 1-hour half-life, leading to more prolonged effects.105
52
Non-Psychostimulant Medications
Cocaine Use Disorder
Bupropion
Bupropion is a dual dopamine and norepinephrine reuptake inhibitor that is FDA-approved

for the treatment of major depressive disorder (MDD), seasonal affective disorder, and
smoking cessation.106 A small amount of evidence exists for bupropion facilitating
abstinence from cocaine use. While bupropion was not found to be superior to placebo on
cocaine abstinence at the end of treatment or on treatment retention, it was superior to
placebo on sustained (ie, 3 or more weeks) abstinence in two RCTs.107,108
Though both desirable and undesirable effects are small, the CGC concluded that the
potential benefits of bupropion outweigh the potential risks. Especially in the context of the
lack of strongly supported medication alternatives, the CGC agreed that bupropion may be
considered as a pharmacotherapeutic option for cocaine use disorder.
Bupropion has been shown to reduce nicotine/tobacco use in patients who smoke
cigarettes or use other nicotine/tobacco products.109 Therefore, the CGC agreed that
bupropion could be given additional consideration for patients with co-occurring tobacco
use disorder (TUD). Given bupropion’s efficacy in treating MDD, the CGC also agreed that
this medication could be given additional consideration for patients with co-occurring
depressive disorders.110
The generic formulation of bupropion is commonly available on medication formularies,

and it is relatively easy to titrate dosing. Bupropion is contraindicated in individuals with
history of seizure or anorexia or bulimia nervosa and should be used with caution in
individuals with elevated seizure risk.111
Cocaine Use Disorder: Bupropion Recommendations
9. For patients with cocaine use disorder, clinicians can consider prescribing bupropion to
promote cocaine abstinence (Low certainty, Conditional Recommendation).
53
• Table 7. Bupropion for Cocaine Use Disorder
Topiramate
Topiramate is an anticonvulsant medication that is FDA-approved for the treatment of

epilepsy and migraine. It is known to have several molecular actions, including blocking
voltage-dependent sodium channels, increasing gamma-aminobutyric acid A (GABA-A)
receptor activity, antagonizing some glutamate receptor subtypes, and inhibiting carbonic
anhydrase.112,113 The evidence for topiramate in cocaine use disorder outcomes is mixed; a
meta-analysis demonstrated a higher rate of continuous stimulant abstinence over three
weeks with topiramate versus placebo.114 While the CGC judged that the evidence only
somewhat favors topiramate, they concluded that topiramate might be considered for
patients with cocaine use disorder, especially those who are highly motivated to achieve
abstinence.
The desirable effects of topiramate are somewhat offset by known side effects
(eg, cognitive effects, paresthesia) and variable tolerability, which can be improved by slow
titration.115 In addition, topiramate can cause appetite suppression, which is an important
consideration when treating patients who are underweight or at risk of being
underweight.115
Topiramate has been shown to reduce alcohol use and is utilized off-label for treatment of
alcohol use disorder (AUD).116 Therefore, the CGC agreed that topiramate could be given
additional consideration for patients with co-occurring cocaine use disorder and AUD.
Cocaine Use Disorder: Topiramate Recommendations
10. For patients with cocaine use disorder, clinicians can consider prescribing topiramate
to reduce cocaine use (Low certainty, Conditional Recommendation).
• Table 8. Topiramate for Cocaine Use Disorder
54
Amphetamine-Type Stimulant Use Disorder

Bupropion
Data from systematic reviews and meta-analyses suggest that bupropion alone is not as
effective for individuals with ATS use disorder with respect to stimulant use and
abstinence outcomes compared to the findings in cocaine use disorder.117–119 However, the
evidence is suggestive of an effect for patients with less than daily ATS use. A subgroup
analysis within a high-quality systematic review showed that bupropion was associated
with higher abstinence rates in patients who used ATS less than 18 days per month and in
patients who were adherent to the medication as confirmed by objective measures.119 No
difference in adverse events between bupropion and placebo was noted in any of the
studies.
Though both desirable and undesirable effects are small, the CGC concluded that the
potential benefits of bupropion outweigh the potential risks. Especially in the context of the
lack of strongly supported medication alternatives, the CGC supported consideration of
bupropion for ATS use disorder, specifically in patients with low- to moderate-frequency
(ie, less than 18 days per month) stimulant use.
Bupropion has been shown to reduce nicotine/tobacco use in patients who smoke
cigarettes or use other nicotine/tobacco products.109 Therefore, the CGC agreed that
bupropion could be given additional consideration for patients with co-occurring TUD.
Given bupropion’s efficacy in treating MDD, the CGC also agreed that this medication could
be given additional consideration for patients with co-occurring depressive disorders.110
Bupropion dosing is relatively easy to titrate, and the generic formulation is commonly
available on medication formularies. Bupropion is contraindicated in individuals with
history of seizure or anorexia or bulimia nervosa and should be used with caution in
individuals with elevated seizure risk.111
Amphetamine-Type Stimulant Use Disorder: Bupropion Recommendations
11. For patients with ATS use disorder with low- to moderate-frequency (ie, less than
18 days per month) stimulant use, clinicians can consider prescribing bupropion to
55
• Table 9. Bupropion for Amphetamine-Type Stimulant Use Disorder
Bupropion and Naltrexone
While the evidence for bupropion alone is somewhat weak in patients with ATS use
disorder, two recent studies using combination bupropion and naltrexone have shown
more promise in terms of stimulant use outcomes.120,121 Naltrexone is a mu opioid receptor
antagonist that is FDA-approved for the treatment of AUD and OUD; its extended-release
formulation is also approved for the prevention of OUD recurrence.122 Both studies—one
open label and one RCT—included patients with moderate to severe methamphetamine
use disorder. The CGC considered it appropriate to extend the evidence to other ATS use
disorder populations because the pharmacotherapeutic mechanisms of effect are expected
to be similar.
Because naltrexone is an FDA-approved treatment for AUD, the CGC agreed that
bupropion–naltrexone combination treatment could be given additional consideration for
patients with co-occurring ATS use disorder and AUD. Similarly, this combination could be
given additional consideration for patients with ATS use disorder and co-occurring
nicotine/tobacco use or depressive disorders, because bupropion is FDA-approved for the
treatment of TUD and MDD.
The recommendations in this Guideline do not address the use of bupropion in

combination with naltrexone for patients with OUD. However, clinicians may consider this
combination for patients with co-occurring OUD who are already prescribed naltrexone for
OUD or are in OUD remission and not currently prescribed opioid agonist medication. No
studies were available that evaluated the impact of this medication combination for
co-occurring methamphetamine use disorder and OUD.
With the increasing concurrent use of stimulants and opioids and concerns surrounding
contamination of the stimulant supply with high potency synthetic opioids such as fentanyl,
as well as intentional co-use of stimulants and opioids, an important unanswered research
question is if treatment with naltrexone could be protective against opioid overdose in this
population.
While the evidence for combination bupropion and naltrexone is promising, the CGC noted
a few implementation considerations. The available research used relatively high doses of
bupropion (ie, 450 mg of an extended-release formulation). The standard dosing of
injectable naltrexone is every four weeks for the treatment of AUD and prevention of OUD
recurrence.120,121 In the open label trial, naltrexone was administered every four weeks,
whereas in the RCT it was administered every three weeks to reduce potential blood level
56
fluctuations.120,121 While bupropion and naltrexone are generally well tolerated, both
studies reported a moderate number of adverse events. The combination of these
medications would most likely be prescribed by an addiction specialist, potentially limiting
access and increasing health inequities. Confirmation of the patient’s opioid free status is
required prior to initiating naltrexone.
The trials above evaluated injectable—but not oral—naltrexone in combination with

bupropion for treatment of StUD. While clinical trials have evaluated both oral and
injectable formulations of naltrexone for ATS use disorder, oral naltrexone has not been
studied in combination with bupropion.120,121 At the time of this publication, bupropion and
oral naltrexone are available in generic formulations. The CGC noted that there is no reason
to believe that oral naltrexone would be less effective in this population if the patient is
adherent to treatment, although injectable medications can facilitate adherence. Given the
potential challenges with access to injectable naltrexone, consideration of combination
bupropion and oral naltrexone would be reasonable, particularly for patients who are
highly motivated.
Despite these potential barriers, the CGC concluded that in certain patients, this treatment
option may be useful in reducing ATS use and other co-occurring symptoms.
Bupropion is contraindicated in individuals with history of seizure or anorexia or bulimia

nervosa and should be used with caution in individuals with elevated seizure risk.111
Amphetamine-Type Stimulant Use Disorder: Bupropion and Naltrexone Recommendations
12. For patients with ATS use disorder, clinicians can consider prescribing bupropion in
combination with naltrexone to promote reduced use of ATS (Moderate certainty,
co-occurring AUD, as naltrexone can also reduce alcohol consumption (Moderate
co-occurring TUD, as bupropion can also reduce nicotine/tobacco use (Moderate
c. Clinicians can give this combination additional consideration for patients with
co-occurring depressive disorders, as bupropion can also treat depression
• Table 10. Bupropion + Naltrexone for Amphetamine-Type Stimulant Use Disorder
57
Topiramate
The evidence for topiramate in ATS use disorder outcomes is mixed. Evidence from two
RCTs demonstrated reduction in methamphetamine use via urine drug testing with
topiramate compared to placebo.118,119 Reductions in SUD severity were also found,
suggesting improvements in SUD-related consequences and functioning. Another multisite
RCT found that while topiramate did not increase abstinence for the overall treatment
group, it significantly reduced amount of methamphetamine use and recurrence of use in
the subgroup of individuals who were abstinent at the start of treatment.123
The desirable effects of topiramate are somewhat offset by known side effects
(eg, cognitive effects, paresthesia) and variable tolerability, which can be improved by slow
titration.115 Topiramate can cause appetite suppression; this is an important consideration
when treating patients who are underweight or at risk of being underweight.115
Topiramate has been shown to reduce alcohol use and is utilized off-label for treatment of
AUD.116 While potential effects are small, the CGC agreed that topiramate could be given
additional consideration for patients with co-occurring ATS use disorder and AUD to
reduce use of ATS and alcohol consumption.
Amphetamine-Type Stimulant Use Disorder: Topiramate Recommendations
13. For patients with ATS use disorder, clinicians can consider prescribing topiramate to
reduce use of ATS (Low certainty, Conditional Recommendation).
• Table 11. Topiramate for Amphetamine-Type Stimulant Use Disorder
Mirtazapine
Mirtazapine is an FDA-approved medication for the treatment of MDD that acts at multiple
sites, including adrenergic, serotonergic, and histaminergic receptors.124,125 While meta-
analyses and systematic reviews largely reported mixed or no evidence for mirtazapine,
two randomized placebo-controlled trials showed a small reduction in ATS use.126,127 Both
studies also reported a significant reduction in sexual risk behaviors in patients treated
with mirtazapine compared to placebo. Mirtazapine also had a positive effect on sleep.
While both studies were conducted specifically with men who have sex with men (MSM),
58
the CGC felt it appropriate to extend these results to the general population of patients with
ATS use disorder.
Mirtazapine is widely available and straightforward to prescribe. It is FDA-approved to

treat depression, may also help treat anxiety and improve sleep quality, and has no known
potential for misuse.128 These benefits may be tempered by side effects such as weight gain,
drowsiness, and metabolic issues (eg, poor glucose control) for some patients.
While the evidence is relatively weak, the CGC determined that, because there are few
medication options available, mirtazapine may be preferable to no treatment at all,
particularly for MSM.
Amphetamine-Type Stimulant Use Disorder: Mirtazapine Recommendations
14. For patients with ATS use disorder, clinicians can consider prescribing mirtazapine to
a. Clinicians can give mirtazapine additional consideration for patients with
• Table 12. Mirtazapine for Amphetamine-Type Stimulant Use Disorder
Psychostimulant Medications
A number of psychostimulant medications have been evaluated for the treatment of StUD
(see Appendix K). The CGC recognized that the evidence is relatively limited for the use of
these medications, and evidence demonstrating positive outcomes came from controlled
trials characterized by close physician oversight and frequent monitoring. The medications
discussed in this section have risks that may outweigh their benefits, and many clinicians
may be reluctant to prescribe medications with psychostimulant properties to patients
with StUD. Clinicians should generally avoid use of psychostimulant medications to treat
StUD in patients with histories of stimulant-induced mood disorders.
Given the limitations of current evidence and the inherent risks for prescribing
psychostimulants for StUD, the CGC recommended that only physician specialists board
certified in addiction medicine or addiction psychiatry—or physicians with commensurate
training, competencies, and capacity for close patient monitoring—should prescribe these
medications for this purpose. This level of expertise is needed to conduct the thorough
risk–benefit analysis needed for this complex patient population. ASAM and AAAP will
59
continue to monitor the evolving evidence on this topic and update the recommendations
as appropriate.
When a careful decision is made to prescribe controlled medications, including

psychostimulant medications, clinicians should closely monitor patients and regularly
reassess the risk–benefit profile for each patient to inform potential dose adjustments
and/or tapering when clinically indicated. Clinicians should implement strategies for
monitoring medication adherence and nonmedical use, such as pill counts, PDMP checks,
and drug testing. Extended-release and prodrug formulations are available for several of
the medications listed in this section and should be considered.
While current federal law ** generally prohibits clinicians from prescribing a Schedule II
narcotic drug ††—which 21 USC §802 has defined to include opioid and cocaine analogs—
for the treatment of substance withdrawal or SUD without a specific registration. The
medications outlined in this section do not fall under this definition. However, clinicians
should be aware of state laws where they practice that may restrict prescribing of
psychostimulant medications for StUD.
General Psychostimulant Medication Recommendations
15. Recommendations related to the prescription of psychostimulant medications to treat

StUD are only applicable to:
a. physician specialists who are board certified in addiction medicine or addiction
psychiatry; and
b. physicians with commensurate training, competencies, and capacity for close
patient monitoring (Clinical consensus, Strong Recommendation).
** Prescriptions. 21 CFR §1306 (1971).

†† The term “narcotic drug” means any of the following, whether produced directly or indirectly by extraction
from substances of vegetable origin, independently by means of chemical synthesis, or by a combination of
extraction and chemical synthesis: (A) Opium, opiates, derivatives of opium and opiates, including their
isomers, esters, ethers, salts, and salts of isomers, esters, and ethers, whenever the existence of such isomers,
esters, ethers, and salts is possible within the specific chemical designation. Such term does not include the
isoquinoline alkaloids of opium. (B) Poppy straw and concentrate of poppy straw. (C) Coca leaves, except coca
leaves and extracts of coca leaves from which cocaine, ecgonine, and derivatives of ecgonine or their salts
have been removed. (D) Cocaine, its salts, optical and geometric isomers, and salts of isomers. (E) Ecgonine,
its derivatives, their salts, isomers, and salts of isomers. (F) Any compound, mixture, or preparation which
contains any quantity of any of the substances referred to in subparagraphs (A) through (E).
60
16. When prescribing psychostimulant medications for StUD, clinicians should maintain a
level of monitoring commensurate with the risk profile for the given medication and
patient. Monitoring may include pill counts, drug testing, more frequent clinical contact,
and more frequent PDMP checks (Clinical consensus, Strong Recommendation).
Cocaine Use Disorder

Modafinil
Modafinil is a wakefulness-promoting medication used in the treatment of narcolepsy,

obstructive sleep apnea, and shift work-related sleep disorder.129 The exact mechanism of
action of modafinil is unclear, though in vitro studies have shown that it modulates
multiple neurotransmitter systems, including dopamine, serotonin, and norepinephrine
reuptake, as well as histamine and hypocretin signaling. Modafinil also activates
glutamatergic circuits while inhibiting GABA.130,131
The evidence is mixed regarding the effectiveness of modafinil in reducing cocaine use in
patients with cocaine use disorder. Two meta-analyses found no effect on sustained
cocaine abstinence but a positive effect on cocaine abstinence rates at the end of the
treatment trial in patients treated with modafinil.132,133 Notably, many of the studies
included in the meta-analyses reported low medication adherence rates. Modafinil has
shown more promising efficacy in certain subpopulations, including those without
co-occurring AUD and those with high adherence to treatment. The CGC agreed that
modafinil may be considered, particularly for patients with higher frequency of cocaine use
at the start of treatment.133
Modafinil is generally well tolerated, and the two meta-analyses reported no significant
differences in the rate of serious or other adverse events. The CGC noted that modafinil
inhibits metabolism of hormonal contraceptives and can reduce the effectiveness of this
type of birth control; patients with childbearing potential should be counseled to use an
alternative birth control method. Clinicians should generally avoid use of modafinil or
psychostimulant medications to treat StUD in patients with histories of psychoses, whether
substance-induced or preexisting.134
Cocaine Use Disorder: Modafinil Recommendations
17. For patients with cocaine use disorder and without co-occurring AUD, clinicians can
consider prescribing modafinil to reduce cocaine use and improve treatment retention
61
• Table 13. Modafinil for Cocaine Use Disorder
Topiramate and Extended-Release Mixed Amphetamine Salts
Extended-release mixed amphetamine salts (MAS-ER)—such as Adderall and Mydayis—

are composed of dextroamphetamine sulfate, dextroamphetamine saccharate,
amphetamine aspartate monohydrate, and/or amphetamine sulfate. These medications
increase the release of dopamine and norepinephrine and inhibit the reuptake of these
neurotransmitters.135 While evidence is mixed for topiramate alone, a meta-analysis found
that MAS-ER and topiramate in combination had positive effects for achieving a period of
cocaine abstinence during treatment compared to placebo.136 Additionally, one RCT from
that meta-analysis showed that cocaine craving decreased more rapidly in the treatment
group compared to placebo.137 The CGC noted that these effects may be more pronounced
in patients with more frequent cocaine use.
Because topiramate has been shown to reduce alcohol use and is utilized off-label for
treatment of AUD, the CGC agreed that combination topiramate and MAS-ER treatment
could be given additional consideration for patients with co-occurring cocaine use disorder
and AUD.138,139 Similarly, this combination could be given additional consideration for
patients with co-occurring cocaine use disorder and ADHD as MAS-ER is an effective
treatment for ADHD.140
While the evidence for combination topiramate and MAS-ER is promising, the CGC noted a
few implementation considerations. While both medications are available in generic
formulations, the combination would more likely be prescribed by an addiction specialist,
potentially limiting access and increasing health inequities. Despite these potential
barriers, the CGC concluded that in certain patients, this treatment option may be useful in
reducing cocaine use and other co-occurring symptoms.
Cocaine Use Disorder: Topiramate and Extended-Release Mixed Amphetamine Salts

Recommendations
18. For patients with cocaine use disorder, clinicians can consider prescribing a
combination of topiramate and MAS-ER to reduce cocaine use and cocaine craving
co-occurring AUD, as topiramate can also reduce alcohol consumption (Moderate
co-occurring ADHD, as MAS-ER can also reduce ADHD symptoms (Moderate
62
• Table 14. Topiramate + Extended-Release Mixed Amphetamine Salts for Cocaine Use
Disorder
Amphetamine Formulations
Prescription amphetamine formulations are FDA-approved for the treatment of ADHD and
narcolepsy. These medications increase dopamine and norepinephrine signaling by
increasing the release and inhibiting the reuptake of these neurotransmitters.141 A high-
quality meta-analysis demonstrated that prescription psychostimulant medications—
including modafinil, methylphenidate, MAS-ER, lisdexamfetamine, and
dextroamphetamine—were associated with better cocaine-related outcomes, including
reported sustained abstinence and cocaine-negative urine drug results.136 No difference
was noted on treatment retention. Another meta-analysis reported similar results but
included a broader array of medications, including non-psychostimulant medications
(eg, bupropion).132
The CGC emphasized the importance of adequate dosing. Higher doses of prescription
psychostimulants were associated with the best outcomes for cocaine use disorder.136 The
CGC recognized that clinicians may be hesitant to prescribe higher-than-typical doses of
these medications, particularly given the small sample sizes in the available studies. As
discussed at the beginning of the Psychostimulant Medications section, careful monitoring
and management of risk of misuse and diversion is important when prescribing these
medications.
When prescribing amphetamine formulations, thorough cardiovascular screening (eg, ECG,

stress test) at baseline—including baseline assessment of cardiovascular function—should
be considered, particularly if the patient has underlying risk factors. Clinicians should
monitor for signs and symptoms of cardiovascular dysfunction during the early phase of
treatment. Known effects of psychostimulant medications on blood pressure can be
managed by close monitoring and dose adjustments.
In addition to reduction of cocaine use, there is evidence that psychostimulant medications

can reduce ADHD symptoms in adults with co-occurring ADHD. While a systematic review
showed mixed results,142 these may have been impacted by insufficient dosing (see
Concurrent Management of StUD and ADHD).
63
Cocaine Use Disorder: Amphetamine Formulation Recommendations
19. For patients with cocaine use disorder, clinicians can consider prescribing a long-acting
amphetamine formulation psychostimulant to promote cocaine abstinence (Low
a. Clinicians can give long-acting amphetamine formulation psychostimulants
additional consideration for patients with co-occurring ADHD, as these
medications can also reduce ADHD symptoms (Low certainty, Conditional
Recommendation).
b. When prescribing a long-acting amphetamine formulation psychostimulant,
clinicians can consider dosing at or above the maximum dose approved by the
FDA for the treatment of ADHD to effectively reduce cocaine use (Low certainty,
• Table 15. Psychostimulant Amphetamines for Cocaine Use Disorder
Amphetamine-Type Stimulant Use Disorder

Methylphenidate Formulations
Methylphenidate (MPH) inhibits the reuptake of norepinephrine and dopamine and is FDA-
approved for the treatment of ADHD and narcolepsy.143,144 A high-quality meta-analysis did
not show a significant effect of MPH on amphetamine abstinence overall; however,
subgroup analysis demonstrated that higher doses were associated with short-term
abstinence.136 No difference was noted on treatment retention. Two other systematic
reviews suggested that MPH was associated with reduced use of and craving for
methamphetamine.118,119 Clinical trials suggest that methylphenidate for ATS use disorder
may be more effective with patients who have a moderate or higher frequency of ATS use
at treatment start, which the trials defined as greater than 10 days per month.118,119
In addition to reduction of ATS use, there is evidence that MPH formulations can reduce
ADHD symptoms in adults with ATS use disorder and co-occurring ADHD.140 The CGC
agreed that clinicians could give MPH formulations additional consideration for patients
with co-occurring ATS use disorder and ADHD due to the effects of MPH on ADHD
symptoms.
Clinicians should note the importance of thorough cardiovascular screening at baseline,

including baseline assessment of cardiovascular function. Clinicians should monitor for
signs and symptoms of cardiovascular dysfunction during the early phase of treatment.
64
Known effects of psychostimulant medications on blood pressure can be managed by close

monitoring and dose adjustments.
The CGC recognized that clinicians may be hesitant to prescribe higher-than-typical doses
of these medications but also emphasized that risk of misuse or diversion can be managed.
As discussed at the beginning of the Psychostimulant Medications section, careful
monitoring and management of risk of misuse and diversion is important when prescribing
these medications.
65
Amphetamine-Type Stimulant Use Disorder: Methylphenidate Formulations

Recommendations
20. For patients with ATS use disorder, clinicians can consider prescribing a long-acting
MPH formulation to promote reduced use of ATS (Low certainty, Conditional
Recommendation).
a. Clinicians can give long-acting MPH formulations additional consideration for
patients with moderate or higher frequency of ATS use at treatment start (ie, 10
or more days per month; Low certainty, Conditional Recommendation).
b. Clinicians can give long-acting MPH formulations additional consideration for
patients with co-occurring ADHD, as these medications can also reduce ADHD
symptoms (Low certainty, Conditional Recommendation).
c. When prescribing a long-acting MPH formulation, clinicians can consider dosing
at or above the maximum dose approved by the FDA for the treatment of ADHD
to effectively reduce ATS use (Low certainty, Weak Recommendation).
• Table 16. Psychostimulant Methylphenidate for Amphetamine-Type Stimulant Use
Disorder
Co-occurring Disorders
This section addresses the most common and/or problematic co-occurring psychiatric
disorders known to be caused by and/or exacerbated by StUDs, including psychosis,
depression, and anxiety. General treatment principles of co-occurring disorders are not
addressed here; rather, this section targets specific factors that would alter clinical
management of either condition. ADHD is addressed in more detail due to the clinical
complexity of utilizing psychostimulant medications in individuals with co-occurring StUD
and ADHD.
The CGC noted that people with StUDs and co-occurring psychiatric disorders experience
additional barriers to accessing and remaining in SUD treatment. Clinicians should
facilitate referrals and access to appropriate care whenever possible. Care should be
coordinated when patients are receiving concurrent care for a co-occurring condition.
66
General Guidance
The CGC agreed that clinicians should treat StUD and any co-occurring psychiatric
disorders concurrently. The CGC recommended that clinicians use an integrated behavioral
treatment approach whenever possible. Integrated care can range from concurrent care
with coordination between providers to treatment by a provider or program that provides
skilled interventions for both conditions and addresses the interactions between them.
Studies on integrated behavioral treatment approaches are limited and heterogeneous in

design, target population, and outcomes of evaluation. Included studies are not specific to
StUD and include approaches that target mixed SUDs and co-occurring depression, anxiety
disorders, or post-traumatic stress disorder (PTSD); findings are mixed, but some benefits
in reduction of substance use or psychiatric symptoms likely apply to populations with
StUD.145–149 Integrated treatment of StUD and co-occurring mental health conditions is
expected to be more convenient and cost-effective for patients than parallel or sequential
treatment models, with benefits likely to largely outweigh risks or harms.
The CGC recommended that symptoms of psychosis related to or co-occurring with StUD be
treated with indicated pharmacotherapy. Almost all evidence for treating symptoms of
psychosis from systematic reviews and meta-analyses is based on stimulant-induced or
unspecified causes of psychosis.114,117,119,150–155 These studies generally noted a large
beneficial effect of pharmacotherapy for both preexisting and stimulant-induced psychosis,
as well as preexisting and stimulant-induced mania. Undesirable side effects would be
similar to those experienced from the use of these medications in any context. The CGC
noted that clinicians should be aware of differences in side effect profiles, particularly
between typical and atypical antipsychotic medications. Clinicians should generally avoid
use of modafinil or psychostimulant medications to treat StUD in patients with histories of
psychoses, whether substance-induced or preexisting.134 Similarly, clinicians should
generally avoid use of psychostimulant medications to treat StUD in patients with histories
of stimulant-induced mood disorders.
If stimulant-induced psychosis or mania is suspected, the CGC suggested that clinicians

consider a gradual taper off antipsychotic medications after a period of symptom
remission. No evidence was found regarding discontinuation of antipsychotic medications
in this context; however, the CGC considered the desirable effects from protection against
unnecessary exposure to and development of known adverse effects of chronic
antipsychotic or mood stabilizing medications (eg, lithium, valproate). The only
undesirable effect noted was the risk of recurrence of psychotic symptoms; no reliable
evidence was found to predict the risk of symptom recurrence after tapering using factors
such as history of psychosis or symptom severity. Thus, the CGC concluded that the benefits
of tapering outweigh potential risks, particularly for patients with stimulant-induced
psychosis or mania.
67
Symptoms of depression, anxiety, insomnia, and/or attentional problems are commonly

observed during periods of ongoing stimulant use and withdrawal. While these symptoms
often resolve with effective management of withdrawal, the CGC recommended considering
initiation of pharmacotherapy if warranted based on symptom severity and chronicity,
even if symptoms are judged to be stimulant induced.
When initiating treatment for StUD in patients with preexisting co-occurring psychiatric
disorders, the CGC recommended continuing current medications when appropriate and
with consideration for their safety in the context of potential continued use of stimulants or
other substances. Despite the lack of direct evidence, continuing a patient’s medications for
co-occurring psychiatric disorders while reviewing their treatment history and plan and
integrating treatment for StUD is likely to yield improved outcomes in psychiatric disorder
management compared to discontinuation of treatment in the majority of cases,
particularly when psychiatric symptoms are severe or persistent.156,157
Clinicians should be aware that adherence to and effectiveness of medications for

psychiatric conditions is likely to be reduced in the context of ongoing stimulant use.
Additionally, unknown potential adverse interactions between medications and stimulants
could occur. The CGC noted that clinician expertise in both StUD and psychiatric disorders
is helpful when treating patients with co-occurring conditions.
General Guidance Recommendations
21. Clinicians should treat both StUD and co-occurring disorder(s) concurrently (Very low
22. Clinicians should use an integrated behavioral treatment approach that addresses both
conditions when available (Very low certainty, Strong Recommendation). Otherwise,
clinicians should tailor recommended behavioral therapy for StUD (eg, CM, CBT, CRA)
to address possible interactions between a patient’s StUD and co-occurring disorder(s)
23. Symptoms of psychosis or mania should be treated with indicated pharmacotherapy
a. If stimulant-induced psychosis or mania is suspected, clinicians should consider
a gradual taper off antipsychotic medication after a period of remission of
psychotic symptoms (Moderate certainty, Strong Recommendation).
68
24. When developing a treatment plan for symptoms of depression, anxiety, insomnia,
and/or attentional problems observed during periods of stimulant use or withdrawal,
clinicians should:
a. consider pharmacotherapy based on symptom severity and duration, even if
symptoms are stimulant induced (Very low certainty, Strong Recommendation);
and
b. consider whether the patient’s clinical presentation follows the expected time
course of stimulant-induced symptoms given the phase of use (ie, active use,
waning intoxication, acute withdrawal, post-acute withdrawal, post-withdrawal
abstinence) or are present at other times (Very low certainty, Strong
Recommendation).
25. Clinicians initiating treatment for StUD in a patient with a preexisting co-occurring
diagnosis should:
a. review the patient’s existing treatment plan, ideally in coordination with the
patient’s existing treatment provider(s) (Clinical consensus, Strong
b. continue current medications as appropriate (Clinical consensus, Strong
Recommendation), with consideration for safety in the context of the patient’s
potential continued use of stimulants and other substances (Clinical consensus,
Please see the supplementary EtD document for the following summaries of evidence,
relevant citations, and CGC judgments:
• Table 17. Integrated Care
• Table 18. Psychosis
• Table 19. Psychosis Taper
• Table 20. Other Symptoms
Concurrent Management of StUD and ADHD

Management of ADHD in patients with ongoing use of nonprescribed stimulants may be
challenging. Clinicians should be aware that nonmedical use of prescription stimulants
does not preclude the presence of ADHD; studies have shown high levels of co-occurring
psychiatric disorders, especially ADHD, in the context of chronic use of stimulants.156,158 A
biopsychosocial assessment for StUD should include screening for ADHD, and assessment
and treatment should be offered—directly or through referral—if indicated.159
Evidence supports the use of multimodal interventions, including psychostimulant

medications, to treat ADHD in individuals with co-occurring StUD.142 Some—but not all—
69
studies have demonstrated significant reduction in ADHD symptoms associated with

psychostimulant prescription in individuals with StUD without an increase in stimulant
misuse.142,160 Non-stimulant medications for the treatment of ADHD—such as atomoxetine,
off-label clonidine, and off-label bupropion—may be considered in individuals with StUD,
although these medications are not judged to be as effective as long-acting stimulant
medications. As with other co-occurring conditions, behavioral interventions should be
considered in conjunction with medication. The CGC noted that individuals with StUD who
have acquired tolerance for the effects of stimulants may require higher doses of
prescribed psychostimulant medications to reach clinical benefit.
The use of prescription stimulant medications, which are controlled substances, remains
controversial due to the perceived risk of medication misuse and/or development of
tolerance and StUD.161 No research was found on the effectiveness of strategies to prevent
nonmedical use and diversion of stimulant medications among patients with co-occurring
StUD and ADHD. Evaluations of risk mitigation strategies are found in studies of patients
with ADHD, but these focus on the prevalence of practices to prevent stimulant medication
diversion and misuse rather than their efficacy.142,162 Despite the lack of research in this
area, the CGC emphasized the importance of establishing risk mitigation measures.
Clinicians should review the PDMP prior to prescribing stimulants to any patient with SUD,
especially StUD. Use of extended-release ‡‡ or prodrug formulations can mitigate risks
related to misuse and the addictive potential of prescription stimulants by producing less
rapid onset of effect, maintaining more steady serum levels of medication, and/or
preventing or reducing effects when alternative routes of administration are used.
However, health insurance coverage may vary. Other strategies that clinicians can consider
to mitigate risks in accordance with standard precautions for prescribing controlled
substances include monitoring via drug testing, conducting pill counts, and increasing
frequency of visits to facilitate adequate clinical monitoring.
Similarly, no research was found on the effectiveness of strategies to prevent nonmedical

use and diversion of stimulant medications among adolescent or young adult patients with
co-occurring StUD and ADHD. Arranging for a parent, guardian, or other trusted adult to
directly observe adolescent patients’ medication administration is recommended to reduce
the likelihood of nonmedical use. Further, conducting pill counts and counseling families on
safe storage of controlled medications is in accordance with standard precautions for
prescribing controlled substances. See Adolescents and Young Adults for more information
on managing StUD in this patient population.
‡‡Including osmotic-controlled release oral delivery system (OROS) and spheroidal oral drug absorption
system (SODAS) medications.
70
When prescribing stimulant medications, clinicians should monitor for adverse effects,
including secondary hypertension and other cardiac outcomes. Preexisting hypertension,
cardiovascular disease, or psychosis should prompt greater caution in using
psychostimulants to treat ADHD in StUD.
Concurrent Management of StUD and ADHD Recommendations
26. For patients with co-occurring StUD and ADHD, clinicians should address ADHD
symptoms as part of the treatment of StUD (Low certainty, Strong Recommendation).
Clinicians should consider:
a. prescribing psychostimulant medications to manage ADHD when the benefits of
the medication outweigh the risks (Low certainty, Strong Recommendation),
b. prescribing non-stimulant medications to manage ADHD when the benefits of
psychostimulant medications do not outweigh the risks (Low certainty, Strong
c. behavioral approaches (Low certainty, Strong Recommendation).
27. When prescribing psychostimulant medications to a patient with co-occurring StUD and
ADHD, clinicians should consider:
a. using extended-release formulations (Clinical consensus, Strong
b. maintaining a level of monitoring commensurate with the risk profile for the
given medication and patient—monitoring may include pill counts, drug testing,
more frequent clinical contact, and more frequent PDMP checks (Clinical
28. For adolescent and young adult patients with co-occurring StUD and ADHD, clinicians
should additionally consider:
a. arranging for a parent, health professional (eg, trained school nurse), or other
trusted adult to directly observe administration of the medication, especially if
using a short-acting formulation (Clinical consensus, Strong Recommendation);
and
b. counseling families on the importance of safely storing and restricting access to
controlled medications (Clinical consensus, Conditional Recommendation).
• Table 21. ADHD
71
Population-Specific Considerations
Adolescents and Young Adults
The 2021 National Survey on Drug Use and Health (NSDUH) reported that among
adolescents (ie, ages 12 to 17), 1.2% reported nonmedical use of prescription stimulants,
0.2% reported use of cocaine, and 0.1% reported use of methamphetamine in the past
year.163 Stimulant use rates are higher among young adults (ie, ages 18 to 25): 3.7%
reported nonmedical use of prescription stimulants, 3.5% reported use of cocaine, and
0.5% reported use of methamphetamine in the past year.163 In the US, the peak age for
initiating nonmedical use of prescription stimulants is 16 to 19 years, and the median age
of initiation of cocaine and methamphetamine use is approximately 20 years.164,165
Adolescents and young adults often cite cognitive enhancement as a reason for prescription
stimulant misuse.166
StUD is rare among adolescents, with 0.1% meeting criteria for methamphetamine use
disorder, 0.0% for cocaine use disorder, and 0.9% for prescription stimulant use disorder
in 2021. Among young adults, 3.5% met criteria for a prescription stimulant use disorder,
0.6% for methamphetamine use disorder, and 0.6% for cocaine use disorder. Adolescents
with ADHD are at increased risk for SUD compared to the general population.167 However,
research has shown that pharmacological treatment of ADHD in this population, including
with psychostimulant medications, reduces the risk for development of SUD.168
Clinicians should provide adolescents and young adults who use stimulants with the same
treatment, harm reduction, and recovery support services (RSS) as adults in a
developmentally responsive manner. Similarly, standard multimodal interventions,
including pharmacotherapy, should be used to treat ADHD in adolescent and young adult
patients with this co-occurring disorder.169 Clinicians should be aware that patients may
not always take their psychostimulant medication daily and may accumulate a surplus of
medications which can be a source of misuse and diversion.170 See the American Academy
of Child and Adolescent Psychiatry’s (AACAP) guide on Medication: Preventing Misuse and
Diversion for additional discussion.171
Clinicians should evaluate the “set and setting” to understand the context for adolescent
and young adult substance use as part of their clinical assessment. Set and setting refer to
the patient’s mindset and the social and physical environment(s) where they use
substances. The context of use should inform the assessment of substance use-related risks
and risky SUD-related behaviors. When treating adolescents and young adults, clinicians
should always evaluate for co-occurring mental health conditions and integrate treatment
for co-occurring conditions and other psychosocial needs into the treatment plan for StUD.
72
When treating adolescents and young adults, the CGC noted that it is especially important
to seek additional sources of collateral information beyond family members—such as
teachers, guidance counselors, coaches, and roommates—with patient permission. This is
also important when establishing a late diagnosis of ADHD in patients with StUD, which
requires symptoms to present prior to age 12, even if the diagnosis is made later. However,
collateral sources who are able to account for symptoms that started before the StUD may
not always be available, which can present significant challenges for the clinician.
Adolescent and Young Adult Assessment and Treatment Planning
The assessment and treatment planning recommendations defined earlier in this Guideline
apply to all patients, including adolescents and young adults. This section presents unique
considerations related to the adolescent and young adult population.
The CGC noted that building trust with adolescent and young adult patients and conducting
careful clinical interviews are the preferred approaches to determine whether adolescents
and young adults are misusing stimulants. While building and maintaining trust are
important in all clinical encounters, it is especially critical when engaging adolescents and
young adults in the SUD assessment and treatment process. Evidence has shown that when
clinicians provide assurance of confidentiality, adolescents and young adults are more
likely to disclose substance use and other sensitive information.172
Data are limited on the potential benefits and harms of drug testing for adolescents and
young adults with StUD. While drug testing can be a helpful adjunct to clinical assessment
for StUD—especially when symptomatology is unclear or collateral information is
unavailable—it should be accompanied by careful clinical interview and physical
examination. However, the CGC recommended against the routine use of drug tests to
screen or monitor for stimulant use in primary care and other general medical settings
because it can degrade trust, particularly when such testing is performed without patient
permission.173 Further, the CGC recognized that drug testing may result in false negatives
and positives and should only be performed by clinicians with expertise pertaining to its
correct use. When considering drug testing in patients under the age of 18, clinicians
should ask the patient for permission to test, even if parental/guardian consent was given.
While adolescent and young adult patients with StUD can present with a range of
co-occurring mental health conditions (eg, depression, anxiety), clinicians should pay
particular attention to signs or symptoms of ADHD and eating disorders, as these are
73
particularly common comorbidities in these populations.21–24 In some cases, adolescents

and young adults who misuse stimulants do so to address underlying symptoms of ADHD
or, in other cases, to lose weight as part of an eating disorder. Although no clinical trials
have been conducted that examine StUD treatment outcomes when underlying ADHD or
eating disorders are treated, a general principle in the care of adolescents and young adults
with SUD is to address underlying mental health conditions with an integrated approach.
Similar to adults, adolescents and young adults who use stimulants present with a wide
range of other assorted issues, including risky sexual behaviors. A meta-analysis showed a
relationship between general substance use and risky sexual behaviors, such as
unprotected sex and multiple partners among adolescents.174 Psychosocial screening for
adolescents who use stimulants should include screening for risky sexual behaviors. If the
screen is positive, clinicians should follow the recommendations for the general population
outlined in Secondary and Tertiary Prevention.
Ideally, adolescent and young adult patients would be referred to age-specific treatment
and other support programs to address identified biopsychosocial needs, including
programs to address food or housing insecurity or transportation needs. However, the CGC
noted that few such programs exist, depending on the region, and emphasized that the lack
of available specialized programs should not delay or preclude initiation of treatment.
Adolescent and Young Adult Assessment and Treatment Planning Recommendations
29. Clinicians should avoid routine drug testing to screen adolescents and young adults for
StUD (Clinical consensus, Strong Recommendation).
a. When considering drug testing in patients under the age of 18, clinicians should
ask patients for permission to test, even if parental/guardian consent was given,
unless obtaining assent is not possible (eg, loss of consciousness; Clinical
30. Clinicians should pay particular attention to signs or symptoms of ADHD and eating
disorders in adolescent and young adult patients (Clinical consensus, Strong
Recommendation).
31. If available, clinicians should refer adolescent and young adult patients to age-specific
treatment and support programs to address identified biopsychosocial needs (Clinical
74
Adolescent and Young Adult Treatment
Despite the relative lack of evidence on adolescent- and young adult-specific treatment for
StUD, the CGC concurred on a number of interventions and other strategies that are
reasonable based on their effectiveness in adolescents and young adults with SUDs in
general and/or their effectiveness for adults with StUD.
Specifically, the CGC agreed that clinicians should consider delivering behavioral
interventions that have been demonstrated to be effective in the treatment of other SUDs in
adolescents (eg, CM, CBT, CRA, family therapy) and in the treatment of StUDs in adults
(eg, CM, CBT, CRA).
While data are available regarding the efficacy of CM and family therapy for adolescents
and young adults with SUD, data evaluating other therapy modalities (eg, CBT, CRA) are
lacking.175,176 The recommendations related to these other modalities are based on studies
evaluating these therapies in adolescents and young adults with other SUDs, adults with
StUD, and clinical experience. Various therapy modalities can be offered; some adolescents
and young adults may find one or a combination of therapies most beneficial for StUD.
Treatment plans should be adjusted based on the individual’s response to treatment.
While there are no data on adolescent- and young adult-specific or developmentally

responsive treatment specific to StUD, the standard of care for adolescent- and young adult
SUD treatment is to use interventions that are specifically tailored or designed for their
unique developmental stage.177,178,179 Adolescent- and young adult-specific models or
tailored treatment for StUD are expected to be moderately more effective than nonspecific
treatment and less likely to expose patients to peers who use other substances. Given
limited evidence, these recommendations are based on the experiences of clinicians with
subject matter expertise in treating adolescents and young adults with StUD.
Adolescent and young adult patients should be referred to the level of care appropriate for
providing safe and effective treatment while maintaining the least restrictive environment.
Clinicians should tailor a referral that is adolescent- and young adult-specific, accessible,
and encourages ongoing contact and support. Peer-based services may provide adolescents
and young adults with an additional level of support.
CM in combination with other behavioral health interventions has been shown to have a
small effect on reducing adolescent and young adult cannabis use and increasing treatment
retention compared to behavioral health interventions without CM.180,181 Additionally, in
adults with StUD, CM represents the current standard of care: CM has been consistently
associated with longer durations of continuous abstinence and lower rates of stimulant use
75
than noncontingent reinforcement (ie, rewards that are not contingent on the desired
behavior) and treatment as usual.42 These effects were strongest during treatment and
appeared to decrease gradually over post-treatment follow-ups.
The CGC recommended a few modifications so that CM is delivered in the most

developmentally appropriate manner possible. For example, CM generally uses drug test
results to identify desired behaviors. Adolescent patients may be understandably hesitant
to participate in CM as part of StUD treatment because they do not want their
parents/guardians to be informed of positive results. However, while state laws vary
regarding confidentiality and parental/guardian notification of treatment progress,
clinicians can work with parents/guardians so that positive drug test results are not met
with punitive outcomes. Another possible modification would be for parents/guardians to
supplement CM as part of StUD treatment by offering additional or alternative
developmentally appropriate incentives. For some adolescent and young adult patients,
engaging in prosocial behaviors—such as receiving permission to attend events or spend
time with friends—may be more incentivizing than cash or voucher rewards.
Family Therapy
Current data suggest that family therapy can be more effective than other therapeutic
modalities in reducing substance use in adolescents and young adults with SUDs, but this
research is not specific for StUD.182 However, given the success in reducing other substance
use, the CGC inferred that family therapy could also be effective and appropriate to
recommend for adolescents and young adults with StUD who consent to family therapy. It
is important to recognize that family therapy may uncover other dynamics—including
co-occurring disorders in other family members, challenges in communication between
family members, or more serious issues such as physical or sexual abuse—that may reveal
additional treatment needs and/or impact adolescent and young adult patients’
engagement in continuing family therapy.
Family therapy is often helpful in establishing goals and communication strategies around
substance use and can also allow clinicians to begin to understand how the dynamic of the
family may contribute to ongoing substance use, such as structure, boundaries, and/or
consequences at home. The CGC noted that clinicians should take a broad view on how
family is defined and attempt to identify the persons of significance who can help
individual patients in their treatment and recovery.
For a more detailed discussion, see SAMHSA’s Treatment Improvement Protocol (TIP) 39:
Substance Use Disorder Treatment and Family Therapy.183
76
Group Counseling and Therapy
For behavioral treatment in group formats, the CGC recommended using peer-age groups
when possible and avoiding incorporating adolescents and young adults into group
behavioral treatment with older adults. Clinical experience and best practice approaches
suggest a potential negative influence from combining age groups. Being exposed to older
individuals—who tend to have used substances for longer and, therefore, tend to have
developed more severe SUDs—can reduce the effectiveness of behavioral interventions for
adolescents and young adults and increase their experiences of negative pressure from
other participants.184 Additionally, survey evidence suggests that adolescents and young
adults prefer to be in groups comprised of peers of their own age.185,186
Pharmacotherapy
Clinicians can consider treating adolescents and young adults with StUD with the off-label
pharmacotherapies detailed in the Pharmacotherapy section when the developmentally
contextualized benefits outweigh the harms. Though available clinical trials did not
typically include participants under 18 years of age, it is likely that many of the benefits
observed in adults over 18 years of age would be expected in older adolescents (ie, 16- and
17-year-olds). Given the potentially life-threatening consequences of StUD, the CGC felt that
clinicians might consider pharmacotherapy on a case-by-case basis, balancing potential
benefits and harms. The recommendation to offer pharmacotherapy to adolescents is based
on expert opinion; the recommendation to offer pharmacotherapy to young adults is based
on small amounts of clinical trial data.
Family Involvement
The CGC’s clinical experience suggested that the involvement of family members is often
beneficial in the treatment of adolescents and young adults with SUDs, and trusted adults
should be incorporated when appropriate.187 Though no evidence is available for the role
that family involvement may play in adolescents and young adults with StUD, the CGC
recognized that family involvement can enhance both engagement and efficacy of
treatment in adult populations and would be a worthwhile endeavor to explore with
adolescent and young adult patients. However, clinicians should take into account the
adolescent or young adult patient’s relationship and interest in engaging with their family
to ensure that family members or other trusted adults share a mutual understanding of the
patient’s treatment goals and are equipped with effective methods to provide support.
Clinicians should counsel parents/guardians not to conduct drug tests at home to assess
stimulant use in adolescents and young adults without the oversight of a trained clinician.
The CGC acknowledged the lack of studies on home urine drug testing, but—based on
expert opinion and current recommendations from the American Academy of Pediatrics
77
(AAP) that urine drug testing only be used in conjunction with a careful, confidential
history and physical examination188—the CGC recommended against home drug testing
without the oversight of an appropriately trained clinician to interpret results. Clinicians
should counsel parents/guardians to not conduct drug tests at home to assess stimulant
use in adolescents and young adults without this oversight.
Consent for Treatment
There are unique considerations regarding privacy and confidentiality for adolescent
patients with StUD and common co-occurring health conditions that may differ across
states and jurisdictions. A full discussion of these issues is beyond the scope of this
Guideline and are discussed elsewhere.189–191
For minors under age 18, clinicians should be familiar with state laws on adolescents’
ability to consent to treatment.192,193 All states have laws that describe what minors may
and may not consent to without parental/guardian approval, but there is tremendous
variability between states.192,193 For example, some
state laws address alcohol and substance use, while
some specify only one or the other.192,193 Some In some states, minors can initiate
states prohibit disclosure to parents/guardians, SUD treatment without involvement
some leave this to the clinician’s discretion, and of a parent or legal guardian; in
others require disclosure under certain other states, parental/guardian
circumstances. 192,193 States may also have different consent may be required before
rules (eg, age thresholds) for an adolescent proceeding with some or all aspects
consenting to treatment for SUD versus screening of treatment.186,187
and/or treatment for comorbidities such as HIV and
STIs.189,192,193
The CGC underscored that it is essential for clinicians to understand the laws regarding
care for adolescents in the state(s) where they are licensed to practice. The CGC also
recognized that although all states require parental/guardian consent for most medical
care provided to minors, there are several exceptions. One is provision of health care to
emancipated minors, generally understood to refer to minors who are living apart from
their parents or legal guardians and are financially independent. Minors may be considered
emancipated if they are married, parents, or in the military.194 In general, emancipated
minors can independently consent to all healthcare interventions, including SUD
treatment.189
Parental/guardian consent is not required for treatment of young adults; however,

clinicians should initiate a conversation with young adult patients about whether their
treatment plan might be enhanced by involving a parent/guardian or other trusted older
adult.
78
Adolescent and Young Adult Treatment Recommendations
32. When treating adolescents and young adults for StUD, clinicians should:
a. consider delivering behavioral interventions that have been demonstrated to be
effective in the treatment of other SUDs in adolescents and young adults (eg, CM,
CBT, CRA, family therapy) and in the treatment of StUDs in adults (eg, CM, CBT,
CRA; Low certainty, Strong Recommendation);
b. use an adolescent- and young adult-specific treatment model (eg, adolescent
CRA [A-CRA]) or tailor existing treatments to be developmentally responsive
(Moderate certainty, Strong Recommendation);
c. use peer-age groups for behavioral treatment in group formats when possible
and avoid incorporating adolescents and young adults into group behavioral
treatment with older adults (Very low certainty, Strong Recommendation);
d. consider treating adolescents and young adults with StUD with the off-label
pharmacotherapies detailed in the Pharmacotherapy section when the
developmentally contextualized benefits outweigh the harms (Very low certainty,
Weak Recommendation);
e. counsel parents/guardians to not conduct home drug tests to assess stimulant
use in adolescents and young adults without the oversight of a trained clinician
(Clinical consensus, Strong Recommendation);
f. recognize that involvement of family members is often beneficial in the
treatment of adolescents and young adults with SUDs and involve family
members and/or trusted adults when appropriate (Clinical consensus, Strong
Recommendation);
g. be familiar with state laws on adolescents’ ability to consent to treatment when
treating minors under age 18; in some states, minors can proceed with
treatment without involvement of a parent or legal guardian in their care,
whereas in other states, parental/guardian consent may be required before
proceeding with some or all aspects of treatment (Clinical consensus, Strong
h. understand that while parental/guardian consent is not required for treatment
of young adults, clinicians should initiate a conversation with the young adult
patient about whether their treatment plan might be enhanced by involving a
trusted adult (Clinical consensus, Strong Recommendation).
79
• Table 22. Contingency Management
• Table 23. Other Psychotherapy
• Table 24. Family Therapy
• Table 25. Specific Treatment
• Table 26. Group Treatment
• Table 27. Pharmacotherapy
Pregnant and Postpartum Patients

Pregnant and Postpartum Patients Assessment
Treatment of StUD in patients who are pregnant presents unique clinical challenges.
Patients who are pregnant should be referred to a prenatal care provider if one has not
already been established; however, treatment of StUD should not be delayed or withheld in
the absence of prenatal care. While no direct evidence was found regarding referrals to
obstetric care providers, given the known benefits of prenatal care, such referrals are
expected to be beneficial. Existing guidelines stress using multidisciplinary teams,
providing comprehensive prenatal care, and screening for complications of pregnancy and
fetal health.195–197 Patients presenting with high-risk pregnancies, including fetal health
complications, may warrant management by a maternal-fetal medicine specialist, when
accessible. Coordination of prenatal care and treatment for StUD is encouraged.
Clinicians should review eligibility criteria for locally available programs that specifically
address biopsychosocial needs related to pregnancy and parenting (eg, childcare; Special
Supplemental Nutrition Program for Women, Infants, and Children [WIC]).
Clinicians should pay particular attention to factors that impact pregnancy and fetal
development when screening for acute signs and symptoms, complications, and sequalae
associated with stimulant use. Existing guidelines strongly support screening for blood-
borne pathogens, STIs, depression, and nutritional deficiencies in those using
stimulants.195–197 Management of stimulant intoxication and withdrawal in pregnant
patients is discussed in Stimulant Intoxication and Withdrawal.
While drug testing can be conducted to clarify treatment needs with similar potential
utility in both patients who are pregnant and the general population with StUD or other
SUDs (see Toxicology Testing), the ramifications of a positive test result for patients who
are pregnant may be more severe. Laws that penalize pregnant patients for substance use
serve to prevent them from obtaining prenatal care and SUD treatment, which may worsen
outcomes for both parent and child.198 Drug testing may result in false positive results that
80
are misleading and potentially devastating for the patient. The CGC also noted that overuse
of drug testing is more common in minoritized populations with SUD.199,200
Before conducting drug testing in patients who are pregnant, the CGC recommended that
clinicians be familiar with their state’s requirements on mandatory reporting and
ramifications of reporting. The potential benefits and risks of utilizing drug testing in
patients with StUD who are pregnant should be weighed carefully in a shared decision-
making process. Because drug testing is known to introduce potential bias against
minoritized populations, the CGC recommended the use of consistent standards for
indications to conduct drug testing. Informed consent should be obtained unless there is
immediate clinical need and obtaining consent is not possible (eg, loss of consciousness).
Pregnant and Postpartum Patients Assessment Recommendations
33. Clinicians should incorporate additional elements into the comprehensive assessment
of StUD for patients who are pregnant, including:
a. providing referrals to prenatal care providers if not already established (Low
b. reviewing eligibility criteria for locally available programs that specifically
address biopsychosocial needs related to pregnancy and parenting
(eg, childcare, WIC programs; Low certainty, Strong Recommendation).
34. Coordination of prenatal care and treatment of StUD is encouraged (Low certainty,
35. When screening for acute issues, complications, and sequalae associated with stimulant
use in patients who are pregnant, clinicians should pay particular attention to factors
that impact pregnancy and fetal development (Low certainty, Strong Recommendation).
81
36. Since the ramifications of a positive drug test result for patients who are pregnant may
be more severe than the general populations, before conducting drug testing in patients
who are pregnant, clinicians should:
a. know their state’s requirements on mandatory reporting and ramifications of
reporting (Clinical consensus, Strong Recommendation);
b. weigh the potential benefits with the risks of utilizing drug testing in this
population (Clinical consensus, Strong Recommendation); and
c. obtain informed consent, unless there is immediate clinical need and obtaining
consent is not possible (eg, loss of consciousness; Clinical consensus, Strong
Recommendation).
• Table 28. Prenatal Care Referral
• Table 29. Screen Social Services – Pregnancy & Postpartum
• Table 30. Screen Factors Pregnancy
Treatment of Pregnant and Postpartum Patients
No direct evidence was found on the efficacy and safety of medications for treatment of
StUD in patients who are pregnant. Risk versus benefit for both the patient and fetus or
infant should be considered when medications are used to manage StUD, stimulant
intoxication, or stimulant withdrawal in this cohort. The CGC agreed that concern for fetal
well-being should not be prioritized over the health of the pregnant patient. Risk level often
varies depending upon trimester, and the CGC emphasized that this should be considered.
Treatment of stimulant-induced intoxication and withdrawal in pregnant patients is

addressed in Stimulant Intoxication and Withdrawal.
Wherever possible, clinicians should incorporate psychosocial treatments targeted toward

meeting the additional needs of patients who are pregnant, including parent-focused
(eg, parenting skills training) and family-based treatment modalities. While no direct
evidence addresses the efficacy of additional psychosocial services, clinical judgment
supports provision of these services as very likely to be beneficial. Need for parenting and
family support are expected to be greater in those with StUDs, who often face greater
disintegration of usual social supports and family structure.
Clinicians should consider CM to incentivize attendance at prenatal appointments, if

feasible, in addition to usual targets (eg, stimulant abstinence). Evidence is mixed regarding
the effect of CM on prenatal care participation; studies have found either increased rates of
82
attendance or no significant effect, with two low-quality studies showing a slight increase
in attendance.201 Nonetheless, prenatal care has been shown to reduce negative effects of
substance use during pregnancy; thus, desirable effects of increasing prenatal care
attendance are likely large.
Clinicians should consider providing additional treatment support around the time of birth;
the postpartum period is typically a time of increased stress, which may lead to increased
risk of return to stimulant use and heightened potential for overdose. Some low-quality
evidence suggests that patients may be at increased risk of return to use during the
postpartum period; small studies in cocaine use disorder showed 27% and 41% of
participants returned to use after 3 months and 2 years, respectively.202 The risk of
developing postpartum depression in this population is nearly 20% and corresponds with
higher rates of return to use.203–205 Access to both antenatal and postpartum care continues
to be problematic and subject to significant health inequities in diagnosing and
appropriately managing postpartum depression in minoritized populations.
Pregnant and Postpartum Patients Treatment Recommendations
37. Risk versus benefit to the fetus or infant should be considered when medications are
used to manage StUD, stimulant intoxication, or stimulant withdrawal (Very low
38. Wherever possible, clinicians should incorporate psychosocial treatments targeted
toward meeting the additional needs of patients who are pregnant (Clinical consensus,
Strong Recommendation), including:
a. Parent-focused treatment modalities (eg, parenting skills training; Clinical
b. family-based treatment modalities (Clinical consensus, Strong Recommendation).
39. Clinicians should consider CM to incentivize attendance at prenatal appointments, if
feasible, in addition to usual targets (eg, stimulant abstinence; Low certainty, Strong
Recommendation).
40. Clinicians should consider providing additional treatment support around the time of
birth, as the postpartum period may be a time of increased stress and risk of return to
stimulant use (Very low certainty, Conditional Recommendation).
• Table 31. Pharmacotherapy – Pregnancy & Postpartum
• Table 32. Prenatal Care Incentives
• Table 33. Postpartum Care
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Breastfeeding
Breastfeeding has numerous benefits to the patient and infant; however, breastmilk may
contain high levels of stimulants, which has the potential to harm infants. Although no
known data exist for outcomes in neonates, the CGC recommended against breastfeeding
by patients who are actively using stimulants. Clinicians should provide pregnant and
postpartum patients with proper education and counseling regarding the risk of stimulants
in breastmilk. Support and education should also be provided to patients who have
achieved sustained abstinence from stimulants and desire to breastfeed.
The CGC noted that none of the medications that have been studied for treatment of StUD
are contraindicated during breastfeeding.
Breastfeeding Recommendations
41. Clinicians should educate patients who use stimulants on the risks of use while
breastfeeding and counsel patients not to breastfeed if they are actively using
stimulants (except as prescribed; Very low certainty, Strong Recommendation).
• Table 34. Breastfeeding
Additional Population-Specific Considerations

While studies were found that examined the effectiveness of treatment interventions
within particular populations, the literature review did not identify any studies on
interventions with the specific aim of reducing health disparities in treatment outcomes
across various subpopulations of individuals who use stimulants.
As with most areas of health care, evidence suggests that treatment outcomes for StUD are
impacted by racial-, ethnic-, and gender-related disparities.206–210 These findings may be
due, in part, to the increased prevalence and severity of underlying risk factors that
negatively impact treatment outcomes, such as history of exposure to violence and trauma,
prevalence of co-occurring psychiatric disorders and biomedical conditions, and poverty.
Disparities in the prevalence of StUD among minoritized populations are exacerbated by
longstanding inequities in structural and social determinants of health that pervade
society. These determinants often reflect stigmatizing and discriminatory ideologies—such
as racism, sexism, homophobia, transphobia, and ableism—and actualize as inequitable
resource distribution that limits access to preventive services and quality treatment, which
further drive health disparities. Progress toward achieving health equity can be best
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addressed through structural changes that include but are not limited to the healthcare
system.
Of note, sex- and gender-related disparities and the intersection between sex and gender,
substance use, and victimization should be considered in the context of StUD.211–213 Sex
trafficking and substance use coercion disproportionately impact females. Further, both
cis- and transgender women are significantly more likely to participate in sex work, which
increases risk for victimization.
The legacy of the United States criminal and carceral systems’ punitive approach to
stimulant use—which disproportionately impacts racial and ethnic minoritized
individuals—has been widely documented.214 The CGC did not find evidence of clinical
interventions that demonstrated differences in effectiveness among racial and ethnic
minoritized patients with StUD, though clinicians should consider myriad structural and
program-level changes. Clinicians can advocate for or adopt program-level changes aimed
at reducing disparities in treatment delivery, such as making decisions about practice
settings, focusing on particular patient populations, and implementing workforce
preparations to provide patients with culturally humble and responsive care. Guidelines
aimed at reducing health disparities generally recommend that clinicians receive training
to work effectively with the populations they directly serve.214
Racism and other forms of discrimination are traumatizing.215 In addition, racial and ethnic
minority patients experience more adverse childhood events (ACEs), including greater
exposure to criminal and legal system trauma.216–218 Providing trauma-sensitive care is
especially important when working with patients from populations who are
disproportionately impacted by structural threats to their health and wellness and
experience health inequities. The high co-occurrence of trauma and SUD led the CGC to
recommend that all patients with stimulant intoxication, withdrawal, or use disorder be
screened for trauma (see Assessment). Central to trauma-sensitive care is maintaining an
awareness of trauma; conducting strengths-based, trauma-informed and -responsive
screening that prioritizes patient safety and autonomy; and responding to the impact of
trauma in the patient’s treatment plan. Clinicians should use validated screening
instruments and trauma-sensitive approaches when collecting the clinical histories of all
patients who have or are suspected to have StUD. §§
For more information on trauma-informed care, see SAMHSA’s TIP 57: Trauma-Informed Care in Behavioral
§§
Health Services.219
85
Sexual Orientation and Gender Identity
Sexual and gender minoritized (SGM) individuals include those who identify as lesbian, gay,
bisexual, queer, questioning, asexual, transgender, and/or gender diverse. A meta-analysis
of 13 studies of behavioral interventions that co-targeted mental health, alcohol and/or
drug use, and sexual risk behavior among gay and bisexual men found a small positive
effect on reducing substance use and sexual risk behavior.220 Of 23 studies in a systematic
review of behavioral interventions that address substance use and sexual risk among gay,
bisexual, and other MSM who use methamphetamine, 18 reported a statistically significant
effect in one or more sexual health-related outcomes. The CGC noted that these effects may
be due to increased treatment engagement, which can help reduce substance use, though
this outcome was not specifically examined in the reviews identified. The available
evidence has not evaluated the impact of SGM-affirming programs on substance-specific
treatment outcomes for patients with StUD who identify as SGM. Therefore, the clinical
focus of the CGC’s recommendations was on supporting SGM patients’ overall access to
StUD treatment rather than recommending that all SGM patients obtain SGM-tailored
treatment.
The CGC also noted that not all SGM patients require tailored programming; insistence on
requiring it could lead to decreased access to general programming if misapplied and, in
the worst case, could be used to discriminate against certain populations. However, some
patients may benefit from SGM-focused programs. Clinicians should consider each
individual patient’s needs when making treatment recommendations; for example:
• Is the patient experiencing distress related to their sexual orientation and/or
gender identity?
• Are they comfortable discussing issues related to their sexual orientation and/or
gender identity in a general population setting?
• Does the patient prefer a tailored treatment setting?
The intent of the CGC’s recommendation was to make tailored treatment both more
responsive and more equitably accessible for SGM patients.
Clinicians should be comfortable taking a sexual practice history and capable of

determining when a referral to an SGM-affirming program should be made based on the
patient’s history and/or behavior. Clinicians may want to wait to assess sexual practice
history until sufficient rapport has been established.221
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Sexual Orientation and Gender Identity Recommendations
42. Clinicians should consider referring SGM patients with StUD to SGM-affirming programs
when their history and/or behavior suggest they may not be comfortable fully
participating in a general population setting (eg, distress related to their identities,
difficulties discussing drug-related sexual activities, inner conflicts, trauma histories)
(Low certainty, Strong Recommendation).
• Table 35. Sexual and Gender Minoritized Individuals
Patients with Cognitive and/or Physical Disabilities
Clinicians should recognize that people with physical and cognitive disabilities have higher
rates of StUD and lower rates of treatment engagement than those without these
disabilities.222,223 In addition, StUD is associated with moderate cognitive deficits.224
Patients with severe chronic health concerns tend to have a slower response to treatment
with fewer days abstinent compared to patients without them.225
The literature review did not identify any studies of interventions designed to reduce
barriers to treatment access or completion among people with StUD and physical
disabilities. However, people with physical and cognitive disabilities have complex clinical
needs. When treating patients with physical or cognitive disabilities, the CGC agreed that
clinicians should follow the best practices outlined in SAMHSA’s 2019 Advisory: Mental and
Substance Use Disorder Treatment for People With Physical and Cognitive Disabilities to
increase accessibility of treatment.222Clinicians should remove or mitigate barriers to
accessibility of StUD treatment for people with physical or cognitive disabilities to the
extent possible.226
Patients Involved in the Criminal and/or Legal Systems
Evidence suggests that treatment should be initiated as soon as feasible for individuals in
the criminal and/or legal systems, including within jails and prisons.187,227 Research also
shows that incorporating telephone monitoring and counseling in follow-up care—in
addition to usual care—for patients with cocaine use disorder who have criminal and/or
legal system involvement can reduce recidivism.228 The CGC noted that there is no reason
to expect this practice to be differentially effective for patients with ATS use disorder.
Individuals with SUD are at a significantly greater risk of overdose upon reentry; therefore,
continuity of care is critical during this vulnerable period.229 Clinicians should connect
87
patients with criminal and/or legal system involvement to appropriate support services
(eg, reentry programs, vocational rehabilitation, transportation, housing assistance) on
reentry.187
Patients Involved in the Criminal and/or Legal Systems Recommendations
43. Initiation of treatment for StUD is recommended for individuals in the criminal and/or
legal systems, including within jails and prisons (Clinical consensus, Strong
Recommendation).
Patients Experiencing Homelessness or Unstable Housing
Stimulant use is highly prevalent among individuals who are homeless; a recent systematic
review found that roughly 30% endorsed past year cocaine use.230 Among homeless and
unstably housed women in San Francisco, 47% reported use of cocaine or
methamphetamine in the past 6 months, and 14% of those who did not use stimulants at
baseline initiated stimulant use within 6 months.231
Physical and sexual victimization are common among people who experience
homelessness and use methamphetamine.232 People experiencing homelessness or
unstable housing may use stimulants for functional reasons, such as to increase alertness
and safety while on the street.233
People experiencing homelessness or unstable housing often have highly complex

biopsychosocial needs due to comorbidities or
other factors—such as injecting substances,234
using multiple substances, engaging in
transactional survival sex, and experiencing “Housing First is an effective approach
serious mental illness and other mental health to reducing homelessness in the United
conditions and trauma—that exacerbate or make States. The philosophy of Housing First
it more challenging to manage stimulant use. They is to connect individuals and families
also have high rates of chronic health conditions experiencing homelessness quickly and
and infectious diseases such as HIV and hepatitis C successfully to stable housing without
virus (HCV).187 Attending to this patient preconditions and barriers to entry,
population’s SDOH would be expected to support such as sobriety, treatment for mental
overall health and wellness but not necessarily health and/or substance use disorders,
reduce substance use. Addressing homelessness or service participation requirements.
can help prevent substance use initiation and Supportive services are offered, and it is
progression to SUD.235 This may include linkages up to the individual to decide whether
to available benefits to improve stability of to accept them.”231
housing and care coordination. These strategies —SAMHSA
88
help make treatment more accessible to patients experiencing homelessness, housing

insecurity, food insecurity, and/or poverty.
Homelessness and housing insecurity create significant barriers to both treatment and
recovery. In 2021, the US Department of Housing and Urban Development (HUD) launched
House America: An All-Hands-on-Deck Effort to Address the Nation’s Homelessness Crisis, a
federal initiative to coordinate efforts to address homelessness by providing significant
new resources for housing and promoting a Housing First approach.236 As part of this
initiative, SAMHSA released new guidance on Expanding Access to and Use of Behavioral
Health Services for People Experiencing Homelessness.237
Patients Experiencing Homelessness or Unstable Housing Recommendations
44. For patients experiencing homelessness, housing insecurity, food insecurity, and/or
poverty, clinicians might consider:
a. providing case management services or a referral to a case manager or other
appropriate service provider(s) who can help the patient navigate health and
social safety net resources (Clinical consensus, Strong Recommendation); and
b. providing a referral to a recovery residence based on the patient’s needs
Veterans
While this Guideline does not include any recommendation statements specific to veterans,
the CGC emphasized that veterans should receive the same clinical care as other adults.
Clinicians should be mindful of additional issues faced by veterans, especially psychological
trauma. The CGC viewed health disparities faced by veterans to be driven primarily by
increased exposure to other risk factors for health disparities (see Additional Population-
Specific Considerations) rather than merely their membership in this population. Clinical
considerations for addressing risk factors are covered in other sections (eg, trauma,
disability, homelessness, co-occurring psychiatric issues).
Stimulant Intoxication and Withdrawal

In developing this Guideline, the CGC sought to include recommendations that were
specific to StUD or of increased importance in the treatment of this illness. This section of
the Guideline is focused on the clinical management of signs and symptoms resulting from
stimulant use when it differs from general clinical management. This approach is intended
to give this Guideline more clinical utility and reduce redundancy with other guidelines.
89
However, it is important for clinicians to deliver the full standard of care that should be
provided to any patient with SUD.
Acute intoxication from novel synthetic stimulants such as cathinones (eg, mephedrone)
may present with severe symptoms, including agitation and psychosis. Available drug
screening panels may not include regionally prevalent substances. As such, clinical
presentation may not align with toxicologic findings. However, the principles of
intoxication management outlined below apply similarly.
The recommendations in this section apply to adolescent, young adult, and adult patients.
Where the evidence allowed the GRADE approach to be used, the full evidence profiles can
be downloaded as an online supplement.
Assessment and Diagnosis

The DSM-5-TR criteria are the clinical standard for diagnosis of stimulant intoxication or
withdrawal in the United States.18 Stimulant intoxication and withdrawal, as well as
complications and comorbidities associated with StUD, are primarily diagnosed based on
history, physical examination, and findings from any laboratory and/or toxicology testing.
Common conditions to consider in the differential diagnosis of a patient who presents with
stimulant intoxication are outlined in Appendix C, and recommendations for laboratory
and toxicology testing are discussed in this section.238
Initial and Comprehensive Assessment

Assessment and Diagnostic Tools
No studies were identified that evaluated diagnostic tools for stimulant intoxication or
withdrawal or tools for assessing the severity of stimulant intoxication. While several
studies were found that evaluated tools to assess stimulant withdrawal symptom
severity—including the Obsessive Compulsive Cocaine Scale (OCCS), the Cocaine Selective
Severity Assessment (CSSA), and the Stimulant Selective Severity Assessment (SSSA)—the
CGC determined that these studies mainly provided evidence for their use as research
measures rather than as clinical tools.239–241 No tools were identified for diagnosing or
assessing stimulant intoxication or withdrawal in a clinical context. The CGC discussed the
use of the Poisoning Severity Score (PSS)—a standardized scale for grading the severity of
acute poisoning based on observed signs and symptoms—for intoxication assessment;
however, given the lack of specific evidence, the CGC deemed it more appropriate to use
standard categorizations of sign and symptom severity.242
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Patient Evaluation
No studies were identified that evaluated strategies for diagnosing or assessing stimulant
intoxication or withdrawal. A number of gray literature sources discussed clinical
assessment standards, including US guidelines from SAMHSA and the VA and over a dozen
international guidelines from the UK, Canada, Australia, Germany, and the World Health
Organization (WHO; see Appendix G).116,187,243–245 The recommendations in this Guideline
are based on a review of these guidelines and the clinical expertise of the CGC.
Stimulant intoxication and withdrawal can result in acute issues and complications that
require urgent medical management (see Appendix L). In non-acute care settings, clinicians
should conduct an initial assessment to identify any acute issues and complications of
stimulant intoxication or withdrawal. A basic assessment of vital signs and focused mental
status evaluation can determine the need for urgent or emergent treatment or referral for
further medical evaluation.
When a patient presents in an acute care setting with a toxicologic emergency, standard
management involves responding to urgent and emergent signs and symptoms (eg, airway
and circulation management).246 Interventions may be refined as additional information is
obtained. While laboratory and toxicology testing may provide helpful information,
completion of tests should not preclude or delay initiating supportive treatment for
suspected acute stimulant intoxication or withdrawal.
After addressing any urgent medical or psychiatric concerns, patients should be given or
referred for a comprehensive assessment that includes a stimulant-focused history and
physical examination (including gathering relevant collateral information, if available) and
an assessment of non-acute complications and sequalae of stimulant use (see Appendix M).
The extent of the clinical exam and medical workup for stimulant intoxication and
withdrawal should be based on the patient’s presenting signs and symptoms and severity
of intoxication. Clinical testing (ie, laboratory testing and/or diagnostic imaging) should be
based on the history and physical exam findings. A safety assessment of the patient’s risk of
harm to self and others should also be conducted.
Safety Assessment
People who use stimulants have an elevated risk of suicide and self-harm. Acute
methamphetamine psychosis is associated with particularly high risk for harm.247 A review
of 300 cases from Australian data (2009–2015) found that suicide comprised 18.2% of all
methamphetamine-related deaths.248 The CGC recommended evaluation of suicidality as
part of the routine assessment of patients with a diagnosis of stimulant intoxication or
withdrawal. It is important to use a validated instrument—such as the Columbia–Suicide
Severity Rating Scale (C-SSRS)—when assessing suicidality.249 In the CGC’s clinical
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experience, suicide risk may resolve more rapidly in stimulant withdrawal compared to
other substance withdrawal syndromes. If patients screen positive for suicide risk, they
should be managed according to best practices, including assessment by a qualified mental
health professional and safety assessment, with consideration for the need for involuntary
psychiatric hospitalization.
Psychological Trauma
There is a high co-occurrence of psychological trauma and StUD. Among patients with
lifetime ATS use disorder, 29.3% reported four or more ACEs, 28.7% reported two to three
ACEs, 21.6% reported one ACE, and 20.4% reported no ACEs.250
No studies were identified on implementing routine screening for trauma-related concerns

in patients with stimulant intoxication or withdrawal. Given the strong correlation between
psychological trauma and StUD, the CGC recommended that all patients with stimulant
intoxication or withdrawal be screened for trauma. When intoxication or withdrawal
management is delivered in an acute care setting, the clinician providing follow-up StUD
care can conduct screening following stabilization of the patient’s urgent or emergent signs
and symptoms. Clinicians should use a validated screening instrument and a trauma-
sensitive approach to asking screening questions. ***
When implementing screening for psychological trauma, it is important for treatment

providers to consider how to:
• ensure that staff have adequate training in trauma-informed and -responsive care;
• attend to patient readiness to participate in screening for trauma, which may
include considering delaying screening until the acute effects of stimulant
intoxication or withdrawal have resolved;
• establish psychological safety before raising topics that could be destabilizing;
• use nonjudgmental language; and
• implement EBIs.
Body Stuffing or Packing
Body stuffing or packing is the practice of hiding drugs in the body for the purpose of
concealment. Body stuffing generally refers to smaller amounts of hastily—and often
poorly—wrapped drugs to evade law enforcement detection, while body packing refers to
preplanned and often well-wrapped larger amounts seen in drug smuggling. Body stuffing
For more information on trauma-informed care, see SAMHSA’s TIP 57: Trauma-Informed Care in Behavioral
***
Health Services.219
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or packing can result in more severe and prolonged symptoms of intoxication and should
be managed in acute care settings.
While there are studies comparing imaging techniques to detect body stuffing or packing
and monitoring asymptomatic individuals, limited information was identified on the
appropriate medical workup for a patient who becomes intoxicated from a ruptured
package of body-concealed stimulants.251–255 Given the relative rarity of this event and that
care should be provided in emergency settings by physicians with critical care experience
(eg, medical toxicologists, emergency medicine and critical care physicians), the CGC did
not provide recommendations for managing this population.
Laboratory Testing
Laboratory testing can detect some of the acute issues and complications of stimulant
intoxication and withdrawal. No research was identified on ordering routine or as-needed
laboratory testing in patients presenting with stimulant intoxication or withdrawal. The
CGC agreed that some tests may be considered based on symptomatology and presence of
risk factors. Clinicians should consider a CBC, a CMP; liver function tests (LFTs); and
markers for muscle breakdown (eg, CK, lactate), cardiac injury (eg, troponin), and renal
injury (eg, BCR, urine albumin).
When ordering a CBC, clinicians should be alert to neutrophil levels in patients with
cocaine intoxication or withdrawal.256 Levamisole is a common adulterant in the cocaine
supply and can cause immunosuppression—in particular, neutropenia—and small vessel
vasculitis. The amount of levamisole contaminating the drug supply and the resulting
degree of clinical concern varies by region and over time.
While there is no direct evidence regarding infectious disease screening as part of the
comprehensive assessment for stimulant intoxication and withdrawal, these tests help
identify common comorbid conditions that can then be treated. The higher prevalence of
HIV, hepatitis, and STIs in patients who use stimulants justifies testing. ††† As noted in the
general Assessment section, clinicians should consider all sites of sexual exposure, which
may include urogenital, pharyngeal, and/or rectal, when testing for chlamydia and
gonorrhea.
For some patients, the impact of routine laboratory testing (see Appendix I) could be
substantial given the benefit of early detection and treatment for some conditions (eg, HIV,
hepatitis). For some diagnoses, the effect of early detection and treatment is less
substantial (eg, liver function). Implementing these recommendations should be highly
††† See recommendations compiled by the CDC for infectious disease screening.30
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feasible in hospital and community settings where intoxication or withdrawal management

would occur. However, these settings should have processes in place to facilitate
appropriate follow-up. Health insurance coverage for routine lower value tests (eg, LFTs,
renal function) may vary.
Toxicology Testing
No studies were identified that evaluated the use of toxicology testing as routine
diagnostics for patients with suspected stimulant intoxication or withdrawal. There are
limitations to the utility of toxicology testing for the management of stimulant intoxication
or withdrawal, particularly in emergency settings when samples need to be sent to external
laboratories. Toxicology testing may answer specific questions regarding a patient’s recent
substance use but is limited by the specific test, as some stimulants are not included on
typical screening panels. When performing toxicology testing for stimulant intoxication in
acute care settings, clinicians should be aware of the limitations of the tests used. A tradeoff
exists between the time delay to process a test versus the accuracy and specificity of the
information obtained. Screening (ie, presumptive testing) results are often available but
less accurate than confirmatory tests and have limited utility in acute intoxication or
withdrawal management. Observation of clinical effects and patient self-report are often
more informative and more immediate than toxicology testing.
Despite these limitations, toxicology testing in acute care settings has some potential utility
by providing valuable information to clinicians delivering follow-up StUD care. It can help
inform clinical thinking regarding the differential diagnosis of a patient who presents with
unspecified agitation, confusion, delirium, psychosis, chest pain, seizure, or autonomic
hyperactivity. Toxicology testing can also help identify substances (both prescribed and
nonprescribed) that could potentially produce drug–drug interactions when considering
pharmacotherapy to manage stimulant intoxication or withdrawal. As well, toxicology
testing in acute clinical settings remains important for public health surveillance and
forensics.
Panels used in acute care settings should ideally test for regionally or demographically
prevalent stimulants rather than screening for every testable stimulant. It is critical to
keep in mind that a negative test result only confirms that the particular target of the
test was not detected in the sample. Immunoassays for the cocaine metabolite,
benzoylecgonine, have high sensitivity and specificity, whereas available immunoassays for
amphetamines have lower specificity and often require confirmatory testing.
As discussed in ASAM’s Appropriate Use of Drug Testing in Clinical Addiction Medicine

consensus statement, there are known limitations to urine immunoassays for
amphetamines, and providers should be cautious when interpreting their results. A recent
review found that amphetamine immunoassays are subject to a roughly 4% to 10% false
94
positive rate.257 Confirmatory testing for amphetamines can rule out false positive from
other drugs (eg, bupropion, MPH, pseudoephedrine).258 Clinicians should refer to the test
manufacturer and/or consult with their laboratory to determine the capabilities and cross-
reactivity of specific assays.
If stimulant intoxication is suspected but presumptive testing is negative, clinicians should

consider the possibility of novel psychoactive stimulants. The growing influence of
synthetic drugs and drug adulteration and contamination means that clinicians may be
making treatment decisions in the absence of toxicological confirmation with increasing
frequency. Regional surveillance reporting is often available on the prevalence of novel
psychoactive substances, including stimulants and their frequency of detection with other
substances.
Toxicology testing that is comprehensive, accurate, and interpreted correctly may be useful
for educating patients and providers and, occasionally, as a diagnostic tool. The
informational value of testing depends on the clinical importance of the outcome. For this
reason, testing is unnecessary if the result would not alter the treatment plan (eg, to
confirm stated methamphetamine use in obvious methamphetamine toxidrome) and
becomes more necessary as the outcome becomes more clinically important (eg, to assess
potential pediatric exposure, to differentiate psychiatric decompensation from
methamphetamine-associated psychosis).
It is also important for clinicians to remember that a positive toxicologic test does not
exclude a concurrent medical emergency, which may be the primary cause of the patient’s
clinical presentation. These tests indicate exposure, which may have occurred 72 or more
hours prior. A positive test result may produce an anchoring bias; For example, a patient
presenting with an aortic dissection or epidural abscess may be agitated, tachycardic, and
hypertensive unrelated to any stimulants still detectable in their urine; a positive drug test
may increase the risk that these types of diagnoses are not pursued.
A detailed discussion of considerations regarding patient consent for drug testing is

beyond the scope of this Guideline. Providers should thoroughly explain all rules regarding
confidentiality, consent, and sharing test results with outside entities to patients. For
additional considerations, see ASAM’s Appropriate Use of Drug Testing in Clinical Addiction
Medicine consensus statement (major principles of this document are outlined in
When implementing toxicology testing, clinicians should consider the technical limitations
of the selected matrix and drug panel. Clinicians should understand it is impossible to
95
detect all adulterants or contaminants with toxicology testing and should be careful to
avoid overinterpretation of findings. Patient consent should generally be obtained prior to
testing unless there is an immediate clinical need and obtaining consent is not possible
(eg, loss of consciousness). Clinicians should stay abreast of which stimulants are prevalent
within certain demographics in their region; testing laboratories often track this
information.
Indications for useful toxicology testing, including screening and confirmatory testing,
include but are not limited to when:
• the etiology of signs and symptoms is unclear,
• the clinical findings are not fully consistent with stimulant intoxication alone
(ie, suggestive of other substance exposure), and
• the information is clinically important (eg, to assess potential pediatric exposure, to
differentiate psychiatric decompensation from methamphetamine-associated
psychosis).
Confirmatory testing should be considered when:

• the findings from a presumptive test are inconsistent with findings in the history or
physical exam, and
• presumptive testing is not available for a substance that is important to evaluate
(eg, fentanyl when co-intoxication with opioids is suspected in a region where
fentanyl commonly contaminates the stimulant supply).
Assessment and Diagnosis Recommendations

45. The clinical examination should first identify any acute concerns and complications of
stimulant intoxication or withdrawal that would indicate the patient requires a higher
level of care (Clinical consensus, Strong Recommendation). This includes an assessment
of hyperadrenergic symptoms, including tachycardia, hypertension, hyperthermia, and
agitation (Clinical consensus, Strong Recommendation).
46. The initial clinical examination when evaluating for suspected stimulant intoxication or
withdrawal should include (Clinical consensus, Strong Recommendation):
a. a clinical interview (as feasible),
b. physical examination,
c. observation of signs and patient-reported symptoms,
d. review of any available collateral information, and
e. a safety assessment of the patient’s risk of harm to self and others.
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47. Stimulant intoxication and withdrawal are primarily diagnosed based on the patient
history and physical examination, as well as findings from any clinical, diagnostic,
and/or toxicology testing (Clinical consensus, Strong Recommendation).
48. If some elements of the medical workup are not available in given a setting, the results
from a basic assessment of vital signs and focused mental status evaluation should be
used to determine the urgency of further medical evaluation or referral for more
comprehensive medical evaluation (Clinical consensus, Strong Recommendation).
49. Clinical testing should be based on presenting signs and symptoms and should include a
CBC, a CMP, LFTs, markers for muscle breakdown (eg, CK, lactate [in cases of muscle
breakdown and acidosis]) or cardiac injury (eg, CK, troponin; Clinical consensus, Strong
Recommendation).
50. When analyzing CBC results for patients with cocaine intoxication or withdrawal,
clinicians should be alert to neutrophil levels, as levamisole is a common adulterant in
the cocaine supply and can cause immunosuppression—in particular, neutropenia—
and small vessel vasculitis (Clinical consensus, Conditional Recommendation).
Toxicology Testing Recommendations
51. In patients presenting with stimulant intoxication or withdrawal, clinicians can use
toxicology testing to:
a. inform clinical thinking regarding the differential diagnosis, along with other
clinical information (Clinical consensus, Strong Recommendation); and
b. identify substance use that could produce drug–drug interactions when
considering pharmacotherapy to manage signs and symptoms of stimulant
intoxication or withdrawal (Clinical consensus, Conditional Recommendation).
52. Clinicians should consider the possibility of novel psychoactive stimulants if stimulant
intoxication is suspected but presumptive testing is negative (Clinical consensus,
Setting Determination
No studies were identified that addressed level of care determination when managing the
risks associated with stimulant intoxication and withdrawal. The recommendations in this
Guideline are based on a review of existing guidelines and the clinical expertise of the
CGC.184,244
97
Patients with stimulant intoxication and withdrawal should be managed in a setting that
provides the intensity of care necessary to address the anticipated severity of their
intoxication or withdrawal syndrome. Treatment needs are determined by a number of
dynamic factors, meaning they will change throughout the course of intoxication or
withdrawal. The CGC recommended the use of a multidimensional assessment—such as
that described in The ASAM Criteria—to determine the appropriate clinical setting for the
management of a given patient’s stimulant intoxication or withdrawal.17
Individuals presenting with stimulant intoxication or withdrawal may be treated in lower

acuity clinical settings if emergency interventions are not indicated. Clinical features that
typically indicate the need for emergency medical treatment include high fever, seizure,
chest pain, psychosis, and suicidality.
Some patients should be managed in higher acuity settings because they require close
monitoring in a setting that has the capacity to manage evolving clinical presentations.
Serious co-occurring medical or psychiatric health concerns can be exacerbated by
stimulant intoxication or withdrawal. Co-intoxication with opioids, alcohol, or other
sedatives can alter both the time course and severity of intoxication and acute effects in
unexpected ways. Individuals who have concealed stimulants by consuming or inserting
packages in a body cavity (ie, body stuffing or packing) should be observed in an acute care
setting with ready access to emergency treatment, as it is difficult to know the actual
amount of substance consumed, quality of the packaging, and risk of exposure.
An appropriate treatment setting allows for assessment of acute issues and complications,
screening for acute intoxication potential, monitoring of the intoxication syndrome, and
administration of appropriate clinical interventions. If any of these are not possible in the
current setting due to patient agitation or limitations in staff capability or resources, the
patient should be transferred to a more intensive level of care with the appropriate
capabilities. However, transfers involve some risk, as patients may choose to leave
treatment rather than initiate and engage in treatment elsewhere. The use of health
information technologies and patient navigators may help facilitate effective transfers by
bridging care between settings.
Setting Determination Recommendations

53. Patients with severe clinical concerns or complications related to stimulant intoxication
should be managed in acute care settings (Clinical consensus, Conditional
Recommendation).
54. Some patients with acute stimulant intoxication can be safely managed in lower acuity
clinical settings if (Clinical consensus, Conditional Recommendation):
a. the patient is cooperative with care;
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b. the patient is responsive to interventions (eg, verbal and nonverbal

de-escalation strategies, medications) that can be managed in the clinical setting;
c. the patient is not experiencing more than mild hyperadrenergic symptoms or is
responsive to medications that can be managed in the clinical setting; and
d. clinicians are able to:
i. assess for acute issues and complications of stimulant intoxication,
ii. monitor vital signs,
iii. assess and monitor suicidality,
iv. monitor for worsening signs and symptoms of intoxication and emergent
complications related to stimulant intoxication,
v. provide adequate hydration,
vi. provide a low-stimulation environment,
vii. manage the risk of return to stimulant use, and
viii. coordinate clinical testing as indicated.
Managing Stimulant Intoxication and Withdrawal

Stimulant Intoxication
Mild stimulant intoxication can typically be managed with behavioral and environmental
interventions meant to help the patient feel calm and safe. More severe behavioral
concerns include severe agitation, psychosis, and risk of harm to self or others, which can
be managed by a combination of pharmacotherapies and behavioral and environmental
interventions.
Clinicians can consult with the Poison Center for 24/7 advice through their toll-free
number (800-222-1222), or with their institution’s clinical toxicology service, which may
reduce the duration of hospital stay.259 Expert consultation may be particularly helpful
when medication shortages impact the availability of recommended medications.
Environmental Interventions
Environmental interventions involve isolation in a non-stimulating environment that is

quiet with low lighting. No studies were found on the effectiveness of environmental
interventions for managing stimulant intoxication and withdrawal. The gray literature
search identified multiple clinical guidelines that discuss behavioral and environmental
strategies to help keep patients calm, including guidance from SAHMSA, the American
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Association of Family Physicians (AAFP), the United Nations Office on Drugs and Crime
(UNODC), and other international guidelines.187,243,244 The CGC agreed that treatment
settings should provide a quiet environment to rest, avoid stimulant exposure, and assist
with social support.
Supportive Care
No studies were found on the types of supportive care that should be provided to patients
experiencing stimulant intoxication and withdrawal. Supportive care should be provided
according to best practices for general substance toxicity, including:
• providing vitamins, fluids, and nutritional support, including thiamine and dextrose;
• correcting electrolyte and fluid imbalances; and
• talking to the patient, including:
o orienting to time and place,
o providing reassurance, and
o communicating what they can expect from treatment.
Behavioral and Psychiatric Symptoms of Stimulant Intoxication
The CGC suggested that clinicians follow an established clinical protocol for managing
general agitation when treating stimulant-induced agitation during intoxication or
withdrawal, such as the American College of Emergency Physicians’ (ACEP) Best Practices
in the Evaluation and Treatment of Agitation (Project BETA).260
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Nonpharmacological Management Strategies for Behavioral and Psychiatric

Symptoms
The process of engaging the patient as an active partner in their assessment, treatment, and
recovery is important to alleviating distress and reducing risk. The management of
agitation and psychosis related to stimulant intoxication should start with behavioral
management strategies. The CGC agreed that not all patients with stimulant intoxication
require pharmacological interventions; intoxication management is an evolving process
where the clinician should continuously evaluate a patient’s response to an intervention.
The CGC emphasized that the use of restraints

should be avoided unless absolutely necessary “All patients have the right to be free from
to protect the safety of patients and/or staff. physical or mental abuse, and corporal
While restraints can temporarily prevent punishment. All patients have the right to
violent behavior, their application increases be free from restraint or seclusion, of any
the risk of injury to patients and staff and can form, imposed as a means of coercion,
be psychologically traumatic for patients. discipline, convenience, or retaliation by
Clinicians should administer medications to staff. Restraint or seclusion may only be
reduce agitation whenever a patient is placed imposed to ensure the immediate physical
into physical restraints and closely monitor safety of the patient, a staff member, or
for hyperthermia and dehydration. See ACEP’s others and must be discontinued at the
Project BETA guidelines, the American earliest possible time.”261
Medical Association’s (AMA) Code of Ethics
Opinion 1.2.7: Use of Restraints, and ACEP’s —Centers for Medicare &
policy statement on Use of Patient Restraints Medicaid Services (CMS)
for further discussion.260–262
Pharmacological Management of Behavioral and Psychiatric Symptoms
Richards et al (2015) reviewed six high-quality studies supporting the use of antipsychotics
and benzodiazepines to manage agitation and psychosis.152 In a comprehensive systematic
review, Connors et al (2019) concluded that antipsychotics administered in the context of
acute stimulant intoxication did not pose significant risk for harm (eg, neuroleptic
malignant syndrome [NMS]) to the extent previously thought.263 The gray literature search
identified multiple clinical guidelines that address pharmacological options for
management of agitation and psychosis, including guidance from SAHMSA, AAFP, UNODC,
and other international guidelines (see Appendix G).187,243,244
Pharmacological Management of Agitation
Benzodiazepines are generally considered first-line treatment for the management of

stimulant-induced agitation (see Appendix N for additional agents to consider). Significant
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agitation should typically be managed in acute care settings given the need for a higher
level of monitoring and clinical resources (eg, intravenous [IV] medications, telemetry,
cooling) than are typically available outside of controlled settings. Clinicians should
monitor for medication side effects with usual care.
In situations of severe stimulant-induced agitation refractory to benzodiazepines and

antipsychotics where rapid control of agitation is necessary for patient and/or staff safety
(most commonly related to methamphetamine intoxication), clinicians can consider IV or
intramuscular (IM) ketamine. Onset of IM ketamine is very rapid, which makes it
particularly useful when a patient is experiencing severe agitation such that placing an IV
would be challenging and delay effective care.
Pharmacological Management of Psychosis
ATS use is associated with greater risk for psychosis compared to cocaine use.264 Recent
research suggested that olanzapine or quetiapine may be preferred for the management of
methamphetamine-induced psychosis; however, the evidence is considered low quality due
to the studies’ high risk of bias.150 When managing psychosis prior to confirming the
etiology of stimulant intoxication or withdrawal, clinicians should conduct an evaluation
with a focus on identifying potential causes of the patient’s psychosis other than stimulant
intoxication. Clinicians should focus treatment of psychosis on management of the
underlying causes of the patient’s psychotic symptoms and monitor for medication side
effects with usual care.
Behavioral and Psychiatric Symptoms of Stimulant Intoxication Recommendations
55. Clinicians should evaluate the patient to identify causal factors for agitation and/or
psychosis other than stimulant intoxication; treatment should address all underlying
causes (Clinical consensus, Strong Recommendation).
56. Clinicians should use verbal and nonverbal de-escalation strategies to calm patients
who are agitated, delirious, and/or psychotic to support their cooperation with care
57. Clinicians can consider treating stimulant-induced agitation or confusion with
medication (High certainty, Conditional Recommendation).
a. Benzodiazepines can be considered a first-line treatment for managing
stimulant-induced agitation and/or confusion (High certainty, Conditional
Recommendation).
58. De-escalation strategies should not delay the use of medication to manage patients who
are agitated, delirious, and/or psychotic and at imminent risk for severe complications
(High certainty, Strong Recommendation).
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59. Clinicians should treat stimulant-induced psychotic symptoms with an antipsychotic

medication (High certainty, Strong Recommendation).
a. The urgency, formulation, and duration of antipsychotic pharmacotherapy
should be based on etiology and symptomatology (High certainty, Strong
Recommendation).
b. Clinicians should avoid the use of chlorpromazine and clozapine for stimulant-
induced psychosis as these medications may place patients at increased risk for
seizures (High certainty, Strong Recommendation).
60. For agitation and/or psychosis that is moderate to severe or escalating, clinicians
should:
a. conduct a medical evaluation focused on identifying life-threatening medical
signs and symptoms that require referral for emergent hospital workup and
management (Clinical consensus, Strong Recommendation), and
b. conduct a mental status evaluation focused on evaluating the patient’s danger to
self and others that would require immediate referral for full psychiatric
assessment and/or involuntary containment and evaluation (Clinical consensus,
61. If agitation and/or psychosis does not respond to the setting’s available de-escalation
and/or medication management interventions, clinicians should coordinate transition
to a more intensive level of care (Clinical consensus, Strong Recommendation).
a. When possible, interventions that address agitation, confusion, delirium and/or
psychosis should be initiated while arranging for transport (Clinical consensus,
62. Clinicians should monitor for progression of psychiatric symptoms, breakthrough
psychosis, suicidality, and emergence of trauma-related symptoms; in particular,
suicidality may increase during waning intoxication and acute withdrawal (Clinical
• Table 36. Agitation Medication
• Table 37. Psychosis Medication
Hyperadrenergic Symptoms of Stimulant Intoxication
The literature review identified several studies on the management of hyperadrenergic

signs and symptoms in patients with stimulant intoxication.114,117,118,151–154,263,265 In a
systematic review focused on cocaine-related cardiovascular toxicity, Richards et al (2016)
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concluded that calcium channel blockers may decrease hypertension and vasospasm but
not necessarily tachycardia, whereas benzodiazepines appear safe for non-cardiovascular
related symptoms.153
When assessing stimulant intoxication, clinicians should assess hyperadrenergic signs and
symptoms, including tachycardia, hypertension, hyperthermia, and agitation. Ongoing
monitoring and management of vital signs—especially heart rate and blood pressure—is
critical to prevent complications that may result from untreated sympathomimetic toxicity.
GABAergic agents are the primary treatment for stimulant-related hyperadrenergic
symptoms. Significant hyperadrenergic symptoms should typically be managed in an acute
care setting.
Beta blockers are generally contraindicated in patients with cocaine intoxication and
cardiovascular disease246; this is an area of ongoing controversy in the field. Many experts
recommend alternative medications such as calcium channel blockers, alpha-1 adrenergic
antagonists, alpha-2 adrenergic agonists, and nitric oxide-mediated vasodilators, as
symptoms indicate, to achieve similar effects in patients with stimulant intoxication. It is
important to consider that these pharmaceutical classes may be most beneficial in treating
hypertension and vasospasm but may result in poor control of reflex tachycardia. Limited
data indicate that alpha-2 adrenergic agonists (eg, dexmedetomidine for more severe
symptoms, clonidine for mild to moderate symptoms) are beneficial in treating stimulant-
induced agitation and can also be useful in the treatment of hypertension and tachycardia
and, thus, should be considered in the management of the hyperadrenergic state of
stimulant intoxication.152,153 Clinicians should monitor for medication side effects with
usual care.
If considering pharmacotherapy with a beta blocker, one with concomitant alpha-1

antagonism (eg, labetalol) is preferred due to low risk of unopposed alpha stimulation.
Clinicians should consider consulting with a specialist (eg, cardiologist, medical
toxicologist) in these instances.
Hypertensive Emergency
Two systematic reviews were identified that examined treatment for stimulant-associated
hypertensive emergency.152,153 All evidence came from case reports and case series;
cocaine-associated hypertensive emergencies were successfully treated with
dexmedetomidine, and ATS-associated hypertensive emergencies were successfully treated
with propranolol, sodium nitroprusside, nifedipine, labetalol, and phentolamine.
The CGC determined that hypertensive emergency can be managed with short-acting
agents such as sodium nitroprusside, phentolamine, or dihydropyridine calcium channel
blockers. Long-acting antihypertensives should be avoided because of the risk of abrupt
104
hemodynamic collapse. Additionally, the CGC recommended the use of nitroglycerin if signs
or symptoms of cardiac ischemia are present.
Hyperadrenergic Symptoms of Stimulant Intoxication Recommendations
63. When patients present with hyperadrenergic symptoms, clinicians should provide
ongoing monitoring and management of vital signs—especially heart rate and blood
pressure—to prevent complications that may result from untreated sympathomimetic
toxicity (Clinical consensus, Strong Recommendation).
64. Clinicians should treat patients in a stimulant-induced hyperadrenergic state with
GABAergic agents (eg, benzodiazepines, phenobarbital, propofol); benzodiazepines can
be considered first-line treatment for this purpose (Low certainty, Strong
Recommendation).
65. If the hyperadrenergic state persists despite appropriate improvement in agitation and
neuromuscular hyperactivity following treatment with benzodiazepines or other
GABAergic agent, clinicians can consider adjunctive treatment with the following
medications:
a. A beta blocker with concomitant alpha-1 antagonism (eg, carvedilol, labetalol;
Moderate certainty, Conditional Recommendation).
b. An alpha-2 adrenergic agonist (eg, dexmedetomidine for severe symptoms,
clonidine for mild to moderate symptoms; Moderate certainty, Conditional
Recommendation).
c. Where beta blockers are contraindicated, clinicians can consider other
pharmacological options such as calcium channel blockers, alpha-1 adrenergic
antagonists, alpha-2 adrenergic agonists, and nitric oxide-mediated vasodilators,
with consideration of other clinically relevant signs and symptoms (Moderate
d. While calcium channel blockers, alpha-1 adrenergic antagonists, alpha-2
adrenergic agonists, and nitric oxide-mediated vasodilators may be most
beneficial in treating hypertension and vasospasm, clinicians should be alert to
potential side effects, including poor control over tachycardia or reflex
tachycardia (Moderate certainty, Strong Recommendation).
66. If a patient with stimulant intoxication is experiencing a hypertensive emergency,
clinicians should:
a. use short-acting agents such as sodium nitroprusside, phentolamine, or
dihydropyridine calcium channel blockers (Very low certainty, Strong
Recommendation);
105
b. avoid long-acting antihypertensives to avoid abrupt hemodynamic collapse

(Very low certainty, Strong Recommendation); and
c. use nitroglycerin if the patient exhibits signs or symptoms of cardiac ischemia
• Table 38. Hyperadrenergic Medications
• Table 39. Hyperadrenergic Adjunct
• Table 40. Hypertensive Emergency
Acute Issues and Complications

Acidosis
Acidosis from stimulant intoxication is typically due to a combination of excessive

movement or muscle activity and drug-specific effects (eg, temperature elevation). Seizures
may also contribute to acidosis. In this context, control of agitation, seizures, and
neuromuscular hyperactivity is critical. No studies were identified on managing acidosis
specific to stimulant intoxication or withdrawal. The CGC did not propose any clinical
recommendations for treating acidosis specific to stimulant intoxication or withdrawal; in
general, treating agitation will help address acidosis.
Significant acidosis—that is, acidosis associated with persistent chemistry abnormalities,

persistent neuromuscular agitation, temperature elevation, and/or long duration of
intoxication—should be managed in acute care settings according to best practices.
GABAergic medications are first-line agents for this purpose. IV fluids and cooling can also
help improve acidosis after attenuation of neuromuscular excitation. Temperature should
be closely monitored. In cases of severe acidosis—that is, where acidosis is associated with
other complications (eg, cardiac, hemodynamic)—more acute measures (eg, cardiac and
electrolyte monitoring, administration of sodium bicarbonate) may be indicated.
Chest Pain
Cardiac complications of stimulant use include chest pain with elevated risks for acute
coronary syndrome (ACS) and cardiac-related mortality. Hyperadrenergic states secondary
to stimulant use can lead to hypertension and tachycardia.
Chest pain in patients with stimulant intoxication should be treated with GABAergic
medications, such as benzodiazepines, phenobarbital, or propofol (depending on symptom
severity and level of care). If chest pain does not improve as the signs and symptoms of
106
stimulant intoxication improve, clinicians should evaluate and treat ACS following current
standards of care. If chest pain is not responding or not resolving, clinicians can consider
concomitant treatment with one of the adjunct medications recommended for persistent
hyperadrenergic symptoms.
Historically, beta blockers have been avoided when treating cocaine intoxication due to
case reports theorizing risks associated with unopposed alpha stimulation. Unopposed
alpha stimulation can result in an acute increase in blood pressure and/or coronary artery
vasoconstriction following beta blocker administration. Evidence suggests that this risk is
lower than hypothesized.266–268 Shin et al (2019) conducted a systematic review and meta-
analysis on the use of beta blockers to treat cocaine intoxication and cocaine-associated
chest pain, finding that beta blockers were not associated with adverse events—including
myocardial infarction (MI), myocardial necrosis, or death—during hospitalization and
long-term follow-up.269 However, this issue remains an area of controversy in the field. For
complex cases, consult with cardiology and/or medical toxicology.
Chest Pain Recommendations
67. For patients experiencing chest pain during stimulant intoxication, clinicians should
initiate treatment for the underlying intoxication with GABAergic agents
(eg, benzodiazepines, phenobarbital, propofol) as long as there are no clinical
contraindications (Moderate certainty, Conditional Recommendation).
68. Alternative agents (eg, calcium channel blockers, vasodilators) are generally preferred
for management of cardiac ischemia in patients experiencing stimulant intoxication.
However, if beta blockers are used in patients with stimulant intoxication, clinicians
should consider using a medication with concomitant alpha-1 antagonism
(eg, carvedilol, labetalol). If an unopposed beta blocker was used in a patient who is or
was recently stimulant intoxicated, clinicians should also consider providing a coronary
vasodilator (eg, nitroglycerin, calcium channel blocker). For complex cases, consult with
cardiology and/or medical toxicology (Low certainty, Conditional Recommendation).
69. While treating underlying stimulant intoxication in patients experiencing chest pain,
clinicians should concomitantly evaluate for ACS and other causes of acute chest pain in
stimulant intoxication (eg, pulmonary, musculoskeletal [MSK]). Chest pain that does not
fully resolve as signs and symptoms of stimulant intoxication improve should be
evaluated and treated following current standards of care (Moderate certainty, Strong
Recommendation).
• Table 41. Chest Pain Medication
• Table 42. Chest Pain Management of Cardiac Ischemia
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• Table 43. Chest Pain Evaluation
Dehydration and Electrolyte and Fluid Imbalances
Dehydration is a common consequence of stimulant intoxication that can result in

electrolyte and fluid imbalances. No studies were identified on managing dehydration or
electrolyte and fluid imbalances specific to stimulant intoxication or withdrawal. The CGC
did not propose any clinical recommendations related to these concerns; dehydration and
electrolyte and fluid imbalance should be managed according to standard best practices.
Hyponatremia in the context of stimulant use is typically seen in patients who present with
confusion, reduced consciousness, or seizures caused by water intoxication from excessive
hydration during 3,4-methylenedioxymethamphetamine (MDMA) intoxication.270 In
alignment with existing guidelines, the CGC agreed that stimulant-related hyponatremia
should be managed according to best practices by replacing sodium.270 Patient follow-up
should include routine and ongoing screening for electrolyte levels and renal function.
Hyperthermia
Hyperthermia caused by autonomic hyperactivity during acute stimulant intoxication can

complicate management of intoxication and may require cooling interventions.271 No
studies were found on managing hyperthermia in patients with stimulant intoxication. The
CGC did not propose any clinical recommendations specific to hyperthermia in stimulant
intoxication or withdrawal; hyperthermia should be managed according to best practices.
For severe hyperthermia (ie, generally greater than 40.5°C/105°F), immersion in a cooling
water bath is typically indicated as it is rapidly effective and may be combined with
pharmacological treatment (eg, sedatives, neuromuscular blocking agents) to accelerate
cooling; for less severe hyperthermia, evaporative methods (eg, mist, fan) are
appropriate.272,273
Neutropenia
Neutropenia, while generally rare and transient, can be life-threatening. No studies were
found on managing neutropenia in patients who use stimulants. The CGC did not propose
any clinical recommendations specific to neutropenia in the context of stimulant
intoxication or withdrawal and determined that neutropenia should be managed according
to best practices. While neutropenia typically improves quickly in most patients after
cessation of exposure to levamisole, if neutropenia is not improving and there is concern
for neutropenic fever or infection, clinicians should consider consulting hematology.
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QRS Widening
Cocaine has local anesthetic effects and can cause QRS widening and impaired cardiac
contractility. QRS widening is a particular complication that occurs when large amounts of
cocaine are consumed rapidly, such as in body stuffing or packing, and should be treated in
an acute care setting. If QRS widening or impaired cardiac contractility are identified,
2 ampoules of sodium bicarbonate should be administered in a bolus to improve the
conduction block and contractility, as well as acidosis if present. If sodium bicarbonate is
unavailable, 3% hypertonic saline can be used (200 mL = 2 ampoules of sodium
bicarbonate) for the conduction block.
If QRS widening is not responsive to use of sodium bicarbonate or 3% hypertonic saline or

the patient is in cardiac arrest and not responding to standard advanced cardiac life
support (ACLS) protocol, a 20% lipid emulsion concentration (ie, Intralipid in a 1 mL/kg
bolus [100 mL in an adult]) can be considered for patients with cocaine intoxication or
overdose. Note that this should only be administered in acute care settings.
In animal models and studies of cocaine toxicity, sodium bicarbonate improved blood
pressure and myocardial function.274,275 Literature reviews on the use of sodium
bicarbonate in humans have identified cocaine as one of the causal factors for QRS
widening.276 While improvement in cardiac function is the main goal with sodium
bicarbonate treatment, correction of metabolic acidosis will also occur. However, this
treatment can exacerbate the risk for QT prolongation, if present, by lowering serum
potassium concentrations. In the event of sodium bicarbonate shortages, 3% hypertonic
saline has been used as a sodium replacement, but it does not correct metabolic acidosis.
QRS Widening Recommendations
70. Cocaine has local anesthetic-like effects at sodium channels and can cause QRS
widening with impairment in cardiac contractility during severe cocaine intoxication. If
these issues are identified, in addition to treating intoxication, clinicians should
administer sodium bicarbonate to improve the conduction block and contractility; this
will also improve metabolic acidosis if present (High certainty, Strong
Recommendation).
• Table 44. QRS Widening
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Rhabdomyolysis
In patients with stimulant intoxication, rhabdomyolysis most commonly occurs following

episodes of severe agitation and hyperthermia. No studies were identified on managing
rhabdomyolysis specific to stimulant intoxication or withdrawal. The CGC did not propose
any clinical recommendations specific to rhabdomyolysis in the context of stimulant
intoxication or withdrawal and determined that rhabdomyolysis should be managed
according to best practices, including:
• replacing fluids to ensure a urine output of >2 mL/kg/h;
• avoiding urinary alkalinization as it inhibits amphetamine elimination and instead
focusing primary management strategies on fluid replacement and management of
agitation and hyperthermia;
• following up with routine and ongoing screening of renal function in patients with
movement disorders or seizures; and
• checking serum creatine phosphokinase (CPK) when rhabdomyolysis occurs in
relation to agitation or hyperthermia.
Seizure
No studies were identified that evaluated strategies for assessment and diagnosis of
stimulant-related seizures. Consensus in existing clinical guidelines is to evaluate seizures
according to best practices.187,270,277
While the recommendations below reflect standard treatment for any toxicity- or
withdrawal-related seizures, the CGC included it in this Guideline because of its importance
in this patient population. In animal models of stimulant-induced seizures, GABAergic
agents have shown greater efficacy in reducing seizure recurrence compared to standard
anticonvulsant agents or sodium channel blockers.278 Benzodiazepines are generally
preferred as first-line treatment because of their relatively wide availability and ease of use
rather than superior effectiveness. Phenobarbital and propofol are second-line agents for
management of stimulant-induced seizures, though propofol is preferred if seizures are
severe or refractory. Acute care settings should have order sets for withdrawal seizures,
with considerations for medication shortages.
In cases where a seizure is associated with a complication of stimulant use

(eg, hyponatremia, trauma) rather than stimulant toxicity, standard treatments should be
provided, including standard seizure medications when indicated. If a seizure is
hyponatremia-related, the underlying hyponatremia should be treated by replacing sodium
(see Dehydration and Electrolyte and Fluid Imbalances).
Monitoring can proceed according to standard practices for seizure management. The risks
associated with undersedation (ie, not controlling the seizure) are greater than those
110
associated with oversedation (ie, side effects from medications); side effects can be
anticipated and are tolerable when compared to the harm of recurrent seizures. The risk of
over- and undersedation can be reduced through clinician education on appropriate dosing
and titration.279
If seizures are not controlled by GABAergic medications during severe stimulant

intoxication, clinicians may consider emergently inducing paralysis with monitoring
(ie, EEG). If a patient is at the level of end-organ dysfunction, cooling should be achieved via
medications to inhibit muscle activity (eg, with benzodiazepines) and, potentially, other
strategies (eg, IV fluids, lavage, evaporative cooling, ice baths if life-threatening).
Seizure Workup
Seizures are one of the most severe complications of stimulant toxicity. Over 6% of new
onset seizures are substance-related; in adults, 9% of status epilepticus is substance-
induced.277 Seizures can occur in association with methamphetamine use, with epileptic
seizures being a frequent complication of methamphetamine intoxication.270,280 While
cocaine use is also frequently cited as a cause of seizure, there is some disagreement
regarding the methodological rigor of positive findings outside of those associated with bag
ruptures following body stuffing or packing.281 Some medications, such as bupropion, raise
the risk for seizures. Seizure may be related to hyponatremia when stimulants are used and
is also more likely with polysubstance rather than single substance use.
Established guidelines are available for neurological evaluation of the first episode of
unprovoked seizure in both adolescents and adults.282,283 However, given stimulants’
proconvulsive activity, there is debate over whether all components of this evaluation—
which involves neurology consultation and evaluation, including electroencephalogram
(EEG) follow-up testing—are necessary when the seizure is likely to be stimulant-induced.
Waiving a full workup saves time and resources, including avoiding an overnight hospital
stay and follow-up appointments. However, missed identification of nontoxicologic causes
of seizure is possible.
No studies were identified that evaluated strategies for assessment and diagnosis of
stimulant-related seizures. Consensus in clinical guidelines is that determination for
comprehensive evaluation following a seizure can be made according to best practices
based on symptomatology and presence of risk factors.187,270,277 Common indications for
waiving a comprehensive neurological evaluation following a seizure include:
• known preexisting seizure disorder,
• history of traumatic brain injury (TBI),
• strong family history of epilepsy,
• hyponatremia detected by laboratory testing, and
• the seizure is well-explained by substance use or withdrawal.
111
The consensus of the CGC was that a seizure is well-explained by substance use or
withdrawal when, for example, the patient is known to use medications that lower seizure
threshold (eg, tramadol, bupropion) or has a history of stimulant- or other substance use-
related seizure. In these instances, there is no evidence that a full neurological workup,
which requires significant healthcare resources, is of benefit.
When the etiology of seizure is not well-explained by substance use, the workup and
management should proceed according to usual best practices in an acute care setting.
Even if full neurological workup is waived, clinicians might still order diagnostic testing
(eg, computed tomography [CT] scan of the head) to rule out other etiologies based on
clinical exam findings (eg, neurological findings suggestive of stroke). Additional evaluation
is indicated if seizures recur despite adequate management of stimulant intoxication.
Seizure Recommendations
71. When a patient presents to the ED with seizures following stimulant use, full
neurological workup is not necessary if the seizures are well explained by substance
use or withdrawal (Clinical consensus, Conditional Recommendation).
a. When the etiology of the seizures is not well explained by stimulant use, the
workup and management of seizures should proceed according to usual best
practices (Clinical consensus, Strong Recommendation).
72. For stimulant intoxication-related seizures or concomitant alcohol- or sedative-related
seizures, clinicians should treat with benzodiazepines (High certainty, Strong
Recommendation).
a. If seizures are refractory to benzodiazepines, clinicians can consider treating
with either phenobarbital or propofol (High certainty, Strong Recommendation).
• Table 45. Seizure Medication
Follow-up
Following management of acute intoxication or withdrawal, clinicians should address non-

acute issues identified in the assessment and conduct additional screening or assessment
as appropriate. Some patients may require monitoring for emergence of renal and cardiac
concerns.
112
A nationally representative 2007 survey of Australian adults estimated that 50.4% of

individuals who use stimulants nonmedically would develop a StUD within 14 years of
onset of use.284 Preexisting psychiatric disorders were significantly associated with
increased risk. Screening for StUD presents an opportunity for clinicians to engage patients
in brief interventions using motivational interviewing (MI) or motivational enhancement
therapy (MET) to facilitate referrals for assessment for StUD, if indicated. While existing
evidence suggests that referral to treatment alone does not result in effective engagement
in ongoing care, the benefit of treating those in need of treatment is substantial. Evidence
suggests that patients find referrals to be acceptable.285,286
Follow-up Recommendations
73. Clinicians should screen patients for StUD and engage them in brief interventions using
MI or MET to facilitate referral for assessment for StUD, if indicated (Very low certainty,
• Table 46. Screening, Brief Intervention, & Referral to Treatment (SBIRT)
Stimulant Withdrawal
Abrupt discontinuation or reduction in stimulant use can cause stimulant withdrawal
syndrome. Many patients will experience 12 to 24 hours of somnolence and irritability—
likely due to catecholamine depletion and sleep deprivation.
During periods of abrupt stimulant reduction or discontinuation, clinicians should be

attentive to the patient’s physical and mental health signs and symptoms. The current
standard of care for managing stimulant withdrawal focuses on ameliorating presenting
signs and symptoms and minimizing risks. Behavioral and environmental interventions
should be used to foster a calming environment (see Setting Determination).
A few pharmacotherapies have been investigated for the treatment of stimulant

withdrawal; however, most of the studies are small and of low quality. A 2009 Cochrane
review on treatment of amphetamine withdrawal that included four RCTs involving
125 participants did not find any pharmacotherapies to be effective for treating general
stimulant withdrawal.265 While some preliminary findings have shown potential promise,
outcomes need to be replicated in larger cohorts before adoption in clinical practice.
Medications may help reduce signs and symptoms associated with stimulant withdrawal.
Signs and symptoms that may require pharmacotherapeutic management include agitation,
113
psychosis, depression, and insomnia, among others. Mental health symptoms that are acute
or not resolving as expected as withdrawal symptoms improve can be managed with
antidepressants and antipsychotics, as indicated, in addition to psychosocial interventions.
See Co-occurring Disorders for additional information on determining whether signs and
symptoms are preexisting or induced by stimulant withdrawal, which will influence
treatment planning.
It is important to differentiate between short-term symptoms of stimulant withdrawal and

underlying psychiatric disorders to determine appropriate treatment. When considering
pharmacotherapies, clinicians should always consider the risks (eg, NMS, serotonin
syndrome) and benefits in the context of each patient’s full clinical presentation.
Treating symptoms such as insomnia and muscle aches with over-the-counter (OTC) or
prescription medications may help support ongoing treatment engagement. Nutritional
interventions may also be indicated.
Post-Acute Symptoms of Withdrawal
Many patients with StUD also experience persistent challenges with post-acute symptoms
of withdrawal—including depression, anxiety, insomnia, and paranoia, among others—that
can last for weeks to months. It is important to assess for and treat these symptoms to
reduce the risk for decompensation and return to stimulant use.
Patients may experience increased sleep during the initial withdrawal period, followed by
sleep disturbances that can be persistent. In some patients, this may be managed with
behavioral interventions, including promotion of good sleep hygiene. For more serious or
persistent insomnia, pharmacotherapy may be needed. Existing guidelines provide
guidance on the pharmacological management of insomnia, including the use of
prescription medications such as sedating antidepressants, antipsychotics, antihistamines,
the antihypertensive clonidine, or OTC medications such as melatonin.287
Clinicians should exercise caution when prescribing sedative–hypnotic medications to

manage insomnia secondary to post-acute stimulant withdrawal given the risks associated
with their regular use. When prescribed, the risks and benefits of the medication should be
regularly reassessed.
Monitoring
No studies were found on strategies for monitoring psychiatric or hyperadrenergic
symptoms in patients with stimulant intoxication or withdrawal. The CGC agreed that
clinicians should consider clinically monitoring patients until their mental status and other
114
signs and symptoms of acute intoxication or withdrawal have stabilized to minimize and
prevent adverse events such as risks for falls, altercations, and motor vehicle crashes.
Clinicians should monitor for progression of psychiatric symptoms such as breakthrough
psychosis, suicidality, and emergence of trauma-related symptoms. In particular, suicidality
may increase as intoxication wanes and acute withdrawal begins and should be addressed.
When patients present with hyperadrenergic signs and symptoms, clinicians should
provide ongoing monitoring and management of vital signs—especially heart rate and
blood pressure—to prevent complications that may result from untreated
sympathomimetic toxicity.
Suicidality
No studies were identified on managing suicidality within the context of stimulant
intoxication or withdrawal. Existing guidelines emphasize the importance of monitoring for
and managing suicide risk.288 The CGC determined that suicidality should be managed
according to best practices, including psychiatric consultation, safety assessment, and
involuntary psychiatric hospitalization if necessary. Effective stimulant intoxication and
withdrawal management can reduce the risk for suicide.289
Managing Stimulant Intoxication and Withdrawal in Pregnant

Patients
In general, acute stimulant intoxication and withdrawal in patients who are pregnant
should be managed according to standard practices, including assessment of fetal well-
being, regardless of pregnancy status. As with all patients, clinicians should conduct risk–
benefit assessments to determine the appropriate course of treatment; the risk–benefit
assessment should consider both the patient and the fetus. Concern for fetal well-being
should not be prioritized over the health of the pregnant patient. While some medications
used to treat intoxication or acute withdrawal may pose risks to the fetus, greater risks
may occur as a result of untreated stimulant intoxication or withdrawal. Untreated
withdrawal also increases the risk for return to stimulant use, which poses direct risks to
the fetus.
It is often extremely difficult, if not impossible, to differentiate methamphetamine-induced

hypertension from gestational hypertension. Hypertension in pregnancy and postpartum
should be managed according to best practices, which currently include290:
• labetalol or nifedipine to manage hypertension, and
• magnesium for seizure prophylaxis.
115
Secondary and Tertiary Prevention

This section addresses secondary and tertiary prevention for patients with or at high risk
for StUD. Primary prevention of StUD is beyond the scope of this Guideline.
• Secondary prevention constitutes clinical practices to:

o identify patients who use stimulants in nonmedical ways but do not meet
diagnostic criteria for StUD, and
o intervene to prevent escalation to StUD.
• Tertiary prevention constitutes clinical recommendations to reduce the harm
associated with nonmedical stimulant use, regardless of the presence of a diagnosis
of StUD.
Screening
For patients in general medical settings, screening for substance use, including stimulants,
is an essential first step to identifying potential misuse (ie, nonmedical or nonprescribed
use of substances) and conducting further assessment for risky stimulant use, StUD, and
other conditions that may increase the risk of StUD (eg, ADHD, eating disorders).
Screening involves asking questions about an individual’s substance use and related
risks using validated screening instruments; screening does not involve drug testing.
The US Preventive Services Task Force (USPSTF) recommends screening for substance use,
including stimulants, in primary care settings.2
There is limited evidence on the appropriate frequency of substance use screening in the
general population. Evidence does exist that taking psychostimulants as prescribed does
not increase the risk of developing StUD and that early and intense treatment of ADHD with
psychostimulant medications may even have protective effects against development of
StUD.291,292 A positive screen can indicate the need for counseling or other interventions to
prevent misuse of psychostimulant medications. Therefore, the CGC agreed that clinicians
should consider more frequent screening for stimulant misuse in patients who take
prescribed psychostimulant medications.
Finally, clinicians should check their state’s PDMP prior to prescribing psychostimulant
medications. While the evidence is weak, clinical experience suggests that the information
gained by checking the PDMP can lead to large benefits in patient safety and indicate the
need for patient education and/or treatment interventions.293 The CGC cautioned that
clinicians could misinterpret the PDMP and use it punitively, though the likelihood of this
116
can be reduced through education. The CGC noted the risk of misusing PDMP information
would not preclude the benefit of initiating a conversation about a patient’s prescriptions.
Screening Recommendations
74. When general healthcare providers screen adolescents or adults for risky substance use
per USPSTF guidelines,2 they should include screening for stimulant misuse
(ie, nonmedical or nonprescribed use; Very low certainty, Strong Recommendation).
75. Clinicians should consider more frequent screening for stimulant misuse in patients
who take prescribed psychostimulant medications (Very low certainty, Strong
Recommendation).
76. Clinicians should check their state’s PDMP prior to prescribing psychostimulant
medications (Moderate certainty, Strong Recommendation).
• Table 47. Screening for Stimulants
• Table 48. Screening for Prescription Psychostimulants
• Table 49. Check Prescription Drug Monitoring Program
Assessment
Although the context is different, the medical workup of patients who misuse stimulants
but do not meet the diagnostic criteria for StUD is similar to that for StUD. For patients who
screen positive for stimulant misuse, clinicians should conduct a focused history and
clinical exam to evaluate for complications of use related to route of administration and
type of preparation used and provide treatment or referrals as appropriate.
Evidence suggests that certain patterns of use lead to more negative consequences.294 In
order to properly determine psychosocial and harm reduction service needs, clinicians
should gather information about patterns of stimulant use, including frequency and
amount of use, whether stimulants are used alone or with others, and whether other
substances are used concurrently with stimulants. History of stimulant-related ED visits
and hospitalizations, as well as history of overdose, should also be gathered. Finally,
clinicians should inquire about routes of administration, particularly injection drug use. A
variety of screening tools are available to screen for injection drug use.295
As evidence suggests that risky sexual behaviors are more prevalent in individuals who use
stimulants, clinicians should gather information from the patient about their sexual
117
behaviors to properly determine psychosocial and harm reduction service needs.174 These
include:
• using drugs to enhance sexual experiences (ie, chemsex),296
• not using condoms or lubricants consistently,297
• having a history of bacterial STIs (ie, chlamydia, syphilis, gonorrhea) within the past
six months,298
• being diagnosed with an STI within the past year,297
• belonging to a population that has a high STI prevalence,299
• having a partner(s) at high risk for STIs,297
• having a recent unintended pregnancy or a sexual partner having a recent
unintended pregnancy,298
• having multiple sexual partners,297
• being the receptive penetrative partner (anal or vaginal) without protection,174 and
• having a recent history of being a victim of sexual assault.300
The CGC emphasized that gathering detailed information to tailor harm reduction
interventions (eg, PrEP, education) could have a large potential benefit. The CGC noted that
screening for risky sexual behaviors interacts with factors such as interpersonal and
intimate partner violence (IPV), trauma, race, sexual orientation, and gender. Subgroup
population differences may influence the preferred intervention (eg, transgender, IPV or
trauma history, patients and/or their partners who are HIV positive). While the possibility
exists for patients to experience feelings of stigma or bias, this may depend on clinician
expertise in interviewing. The possibility of confidentiality violations through medical
record documentation exists, but the CGC deemed the likelihood of this happening low. The
CGC concluded that the benefits of identifying individuals who would be helped by targeted
harm reduction interventions outweighed the risks. A variety of validated screening tools
are available to screen for risky sexual behaviors.
Clinicians should consider asking patients about the context of their stimulant use
(eg, chemsex, weight loss, academic or work performance, staying awake), as well as
history of trauma and IPV. While no direct evidence was found supporting this
recommendation, contextualizing the reasons for patients’ stimulant use can facilitate
conversations around harm reduction. While implementation of this practice is
straightforward, clinicians may require training on trauma-sensitive and culturally humble
approaches to ask about the context of substance use in a nonjudgmental and
destigmatizing manner.
Clinical experience suggests that patients who engage in nonmedical use of prescription
stimulants are more likely to exhibit symptoms of ADHD and should be evaluated for
ADHD. While it is unclear whether the underlying rate of undiagnosed ADHD is higher in
people who misuse prescription stimulants in general, the CGC noted that this rate is higher
in college students who use stimulants nonmedically.301 The CGC emphasized that there is
118
currently debate within the field as to the utility of universal screening for ADHD; however,
patients who exhibit symptoms of ADHD not accounted for by stimulant use should be
further assessed by a qualified clinician.
77. For patients who screen positive for stimulant misuse:
a. Clinicians should conduct a focused history and clinical exam to evaluate
complications of use related to route of administration and type of preparation
used and provide treatment or referrals as appropriate (Very low certainty,
b. Clinicians should assess the following to determine harm reduction service and
counseling needs:
i. risky patterns of stimulant use, including:
1. frequency and amount of use, including binge use (High certainty,
Strong Recommendation);
2. use of stimulants with no one else present (High certainty, Strong
Recommendation);
3. concurrent use of prescribed and nonprescribed medications and
other substances, particularly opioids, alcohol, and other central
nervous system depressants (High certainty, Strong
Recommendation);
4. history of overdose (High certainty, Strong Recommendation); and
5. history of stimulant-related ED visits and hospitalizations (High
ii. routes of administration, particularly injection drug use (Very low
certainty, Strong Recommendation); and
iii. risky sexual behaviors (High certainty, Strong Recommendation).
c. Clinicians should consider asking patients about:
i. the context of their stimulant use (eg, chemsex, weight loss, academic or
work performance, staying awake; Clinical consensus, Strong
Recommendation),
ii. trauma (Clinical consensus, Strong Recommendation), and
iii. IPV (Clinical consensus, Strong Recommendation).
119
d. Clinicians should conduct baseline laboratory testing based on clinical

assessment of risk factors (see Assessment; Clinical consensus, Strong
Recommendation).
78. Patients who engage in nonmedical use of prescription stimulants should be evaluated
for ADHD, which may also require treatment (Clinical consensus, Strong
Recommendation).
• Table 50. Assess Route Complications – Prevention
• Table 51. Assess Risky Patterns – Prevention
• Table 52. Assess Risky Sex – Prevention
Early Intervention for Risky Stimulant Use

Interventions to Reduce Risky Stimulant Use
Clinicians should consider providing brief interventions using MI techniques to patients
with any risky stimulant use to encourage them to make changes that will reduce their risk
of harm, including progressing to StUD. While no direct evidence exists to suggest that brief
interventions are effective for stimulant use outcomes, it is a necessary first step to
providing harm reduction education and treatment for stimulant use, which can reduce
harms stemming from use and increase readiness to change and motivation for treatment.
Clinicians should be aware of some of the unique motivators for stimulant use
(eg, chemsex, weight loss, academic or work performance, staying awake) and be prepared
to discuss and suggest safer alternatives and use practices—such as using clean snorting or
injecting equipment, not sharing equipment, not using alone, and keeping opioid reversal
medication (eg, naloxone) on hand—as part of brief interventions for stimulant use. The
benefits of engaging patients in meaningful harm reduction practices are significant (see
Harm Reduction).
Interventions to Reduce Risky Stimulant Use Recommendations
79. Clinicians should consider providing brief interventions to patients with any risky
stimulant use using MI techniques to encourage patients to reduce or stop their use
80. Clinicians should be aware of some of the unique motivators of stimulant use and be
prepared to discuss and suggest safer alternatives as part of brief interventions for
stimulant use (eg, chemsex, weight loss, academic or work performance, staying awake;
Clinical consensus, Strong Recommendation).
120
• Table 53. Early Intervention SBI
Referral to Treatment for Stimulant Use Disorder

While direct evidence for referral to treatment is relatively weak, the CGC judged the
clinical benefits of facilitating treatment for those who need it to be substantial. Therefore,
the CGC recommended that for patients who screen positive for risky stimulant use,
clinicians should conduct or offer a referral for comprehensive assessment for potential
StUD. When making referrals, linkage support—including warm handoffs—should be
provided. For patients who are ambivalent about referrals for StUD assessment or
treatment, clinicians should consider using interventions to enhance motivation for
treatment (eg, MI, MET).
Peer navigators are increasingly being used to help patients access StUD assessment and
treatment. While evidence for this intervention is limited, the CGC noted that the benefits of
effective engagement in treatment are likely substantial and there is no evidence of
harm.302
Referral to Treatment for Stimulant Use Disorder Recommendations
81. For patients who screen positive for risky stimulant use, clinicians should conduct or
offer referrals for comprehensive assessment and treatment for potential StUD with
linkage support, including warm handoffs (Very low certainty, Strong Recommendation).
82. For patients who are ambivalent about referrals for StUD assessment or treatment,
clinicians should consider using interventions to enhance motivation for treatment
(eg, MI, MET; Very low certainty, Strong Recommendation).
83. Clinicians should consider the use of peer navigators to link patients to StUD
assessment and treatment (Low certainty, Weak Recommendation).
• Table 54. Early Intervention Refer to Treatment
• Table 55. Early Intervention Peer Navigation
121
Harm Reduction
According to the principles of harm reduction, clinicians can engage patients who use
stimulants in treatment and prevention services, accounting for patients’ desires and levels
of interest, motivation, and engagement.
Harm Reduction Education

When education is paired with other harm reduction practices, evidence is strong for a
variety of outcomes. The CGC emphasized that education is an important component of
change and relatively easy to implement; the importance of patient education is readily
supported across a range of other medical conditions. Therefore, clinicians should provide
education to patients who use stimulants nonmedically, particularly with respect to safer
stimulant use, injection practices, sexual practices, and overdose prevention.
Harm Reduction Education Recommendations
84. For patients who engage in risky stimulant use, clinicians should:
a. offer basic harm reduction education about safer stimulant use (Low certainty,
b. tailor harm reduction education to the patient’s patterns of substance use
(eg, context of use, route of administration, type of preparation; Low certainty,
c. refer to relevant local harm reduction services as indicated based on the
patient’s clinical assessment (Low certainty, Strong Recommendation),
d. offer harm reduction education on overdose prevention and reversal (High
e. offer harm reduction education regarding safer sexual practices (High certainty,
• Table 56. Education Stimulants
• Table 57. Prevention Refer to Harm Reduction
• Table 58. Education Overdose
• Table 59. Education Sex
122
Overdose Prevention and Reversal

The US is currently experiencing an historic rise in drug overdoses and overdose deaths
due to high-potency synthetic opioids.303 These synthetic drugs, particularly fentanyl and
its analogs, are increasingly used with stimulants.10 Overdose reversal medications such as
naloxone are well known to prevent opioid overdose deaths. To the extent that patients
intentionally or unintentionally use opioids with stimulants, the CGC agreed that education
on and access to overdose reversal medications are likely to be beneficial with relatively
little risk. Therefore, for patients who use stimulants from nonmedical sources or engage
socially with others who do, clinicians should prescribe or distribute overdose reversal
medications (eg, naloxone) or refer patients to locations where they can obtain these
medications in the community (eg, pharmacies). In March 2023, the FDA approved the first
OTC naloxone nasal spray.304
Drug checking is becoming a standard harm reduction practice. Some evidence was found
that people who use substances would use less if fentanyl was detected before use.305,306 At
least one study found that access to comprehensive drug checking services was associated
with reduced overdose rates.305,306 These findings varied by population studied
(eg, festivals, people who inject drugs), and studies focused on opioid use, though people
who use stimulants were not explicitly excluded.
When using drug checking kits, it is important that patients follow package instructions to
avoid false negatives.307 Patients should also understand that these tests have limitations;
similar to point-of-care drug tests used in healthcare settings, these drug checking tests
may not detect all potentially dangerous contaminants in the drug supply. For example,
fentanyl test strips may not detect other highly potent synthetic opioids, including
carfentanil.308 Similar to presumptive drug testing, these test strips may also produce false
positives that may limit patient reliance on the results.
Some harm reduction programs may provide more comprehensive drug checking services,
including Fourier-transform infrared spectroscopy (FTIR), which can assess contaminants
and verify the main component of the sample. While FTIR has high specificity, it has been
shown to have lower sensitivity for detecting fentanyl compared to fentanyl test strips.309
Fentanyl test strips and other drug checking supplies are prohibited in some states;
clinicians should be aware of local laws when advising their use.310
While rare in the US, supervised consumption sites (SCS) are effective at reducing the
incidence of drug use-related morbidity and mortality.311 The impact of SCS varies
depending on the their frequency of use. While SCS are associated with a small reduction in
infections, they are associated with a moderate reduction in risky injection behaviors and a
moderate to large increase in SUD treatment initiation.311 Therefore, the CGC agreed that
clinicians should consider referring individuals who use stimulants nonmedically to local
123
SCS when available. It is important to note that SCS are currently illegal under federal
law.312
Overdose Prevention and Reversal Recommendations
85. For patients who use stimulants from nonmedical sources or are socially engaged with
others who do, clinicians should prescribe or distribute overdose reversal medications
(eg, naloxone) or refer patients to locations where they can obtain these medications in
the community (High certainty, Strong Recommendation).
86. Clinicians should recommend that patients perform comprehensive drug checking,
including using fentanyl test strips, every time they obtain a new batch of stimulants
from nonmedical sources and review the technique for using fentanyl test strips when
permitted by state law (Moderate certainty, Conditional Recommendation).
87. Clinicians should consider referring individuals to local SCS when available (Moderate
• Table 60. Prevention Naloxone
• Table 61. Prevention Drug Checking
• Table 62. Prevention Supervised Consumption
Safer Sexual Practices and Contraception

While no specific evidence was found on referring or providing STI testing to people who
use stimulants, it is known that risky sexual behaviors are more prevalent in this
population, and earlier identification of STIs is beneficial and reduces transmission.174
Therefore, the CGC recommended that clinicians offer or refer for STI testing at least every
three to six months as per CDC and USPSTF guidelines. More frequent testing may be
indicated depending on the individual patient’s risk.
Clinicians can support harm reduction by educating patients about safer sexual practices
(eg, using condoms and lubricant) or offering referrals to local programs that provide
psychosocial sex education and harm reduction interventions. Clinicians should also
inquire about contraceptive practices and related needs to help patients avoid unintended
pregnancies. Further, if patients are engaging in compulsive sexual behaviors that cause
them distress, they may benefit from referral to qualified treatment professionals.
124
Safer Sexual Practices and Contraception Recommendations
88. For patients who engage in risky sexual behaviors, clinicians should:
a. offer or refer for STI testing at least every 3 to 6 months or more frequently
depending on the individual patient’s risk (Moderate certainty, Strong
Recommendation);
i. consider providing information about local STI testing services where
patients can obtain free or low-cost testing (Moderate certainty, Strong
Recommendation);
b. consider offering a referral to a local psychosocial sex education program or
harm reduction program that addresses risky sexual behavior for additional or
continuing harm reduction intervention (Low certainty, Strong
c. offer condoms and lubrication or advice about where to obtain them (Clinical
• Table 57. Prevention Refer to Harm Reduction
• Table 63. Prevention Routine STI Testing
Injection Drug Use

SSPs are associated with safer injection technique; fewer wounds; and reductions in HIV,
HCV, other blood-borne infections, and complicated infections.313–317 Combining the
provision of safe injection supplies with other interventions—such as linkage to treatment
and addiction medications (eg, for co-occurring OUD)—can increase the magnitude of
desirable effects. The CGC acknowledged that lack of community acceptance can be a
barrier to implementing programs focused on safer injection practices; however, concern
that provision of safer injection supplies increases injection drug use is refuted by
evidence.318 Therefore, the CGC recommended that clinicians provide or refer for harm
reduction education on safer injection practices and safe injection supplies.
Harm reduction education related to injection drug use may include safer practices for
preparing an injection, including using new supplies and clean surfaces, limiting overuse of
acidifiers, and preventing injection site infections and vein damage—for example, see the
Lancaster Harm Reduction Project’s guide on Safer Crack Injection.319,320
125
Injection Drug Use Recommendations
89. For patients who inject stimulants, clinicians should:

a. provide or refer for harm reduction education on safer injection practices and
include information specific to the patient’s stimulant(s) and preparation(s) of
choice (eg, safer acid pairings for crack cocaine injection; Low certainty, Strong
b. provide or refer for safe injection supplies and harm reduction services
• Table 64. Education Injection Drug Use
• Table 65. Prevention Injection Drug Use Kits
HIV Preexposure Prophylaxis

Strong evidence exists that PrEP is effective at preventing HIV overall, as well as
consistently across subgroups with the highest risk for HIV.321,322 While this is indirect
evidence (ie, not explicitly tested in people who use stimulants), substantial benefits are
expected. PrEP has not been shown to increase risky sexual or injection behaviors.323 While
PrEP is associated with some undesirable side effects, prevention of HIV is a critically
important outcome. Therefore, in alignment with CDC and USPSTF guidelines, the CGC
recommended that clinicians offer HIV PrEP to patients who use stimulants and are at
increased risk for HIV due to risky sexual behaviors or injection drug use.298,324
HIV Preexposure Prophylaxis Recommendations
90. Clinicians should offer HIV PrEP to patients who use stimulants and are at increased
risk for HIV, including those who:
a. engage in risky sexual behaviors (High certainty, Strong Recommendation),
b. access postexposure prophylaxis (PEP) regularly (High certainty, Strong
Recommendation), and/or
c. inject drugs (High certainty, Strong Recommendation).
Please see the supplementary EtD document for the following related summary of
evidence:
• Table 66. Prevention PrEP
126
Oral Health
People who use stimulants are well known to be at high risk of dental complications—such
as poor dentition, dental caries, and abscesses—and poor oral health is associated with
subsequent malnutrition.325 Therefore, the CGC recommended that clinicians encourage
patients who use stimulants to maintain good oral hygiene and receive regular dental care
and offer referrals to dental care providers if needed. While this recommendation is
straightforward, the CGC recognized challenges with regard to implementation; many
insurance plans do not adequately cover dental care, and clinicians need to be aware of
local resources to make referrals.
Oral Health Recommendations
91. People who use stimulants are at high risk of dental complications, such as poor
dentition, dental caries, abscesses, and subsequent malnutrition. Clinicians should:
a. encourage patients who use stimulants to maintain good oral hygiene and
receive regular dental care (High certainty, Strong Recommendation), and
b. offer referrals to dental care providers if needed (High certainty, Strong
Recommendation).
• Table 67. Prevention Oral Health
Nutrition
People who use stimulants often experience appetite suppression and go for long periods
without appropriate nutrition, placing them at high risk for nutritional deficits such as
malnutrition, cachexia, and sequalae of specific vitamin deficiencies.326 Based on clinical
expertise, the CGC recommended that clinicians inquire about diet, nutrition, and food
security and encourage patients who use stimulants to eat nutritious food.
Nutrition Recommendations
92. People who use stimulants may experience appetite suppression and go for long
periods without appropriate nutrition, placing them at high risk for nutritional deficits
such as malnutrition, cachexia, and sequalae involving specific vitamin deficiencies.
Clinicians should:
127
a. inquire about diet, nutrition, and food security (Clinical consensus, Strong
b. encourage patients who use stimulants to eat nutritious food (Clinical consensus,
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164
Appendix A. Glossary of Terms

addiction: A treatable chronic medical disease involving complex interactions among brain
circuits, genetics, the environment, and an individual’s life experiences. People with
addiction use substances or engage in behaviors that become compulsive and often
continue despite harmful consequences. Prevention efforts and treatment approaches for
addiction are generally as successful as those for other chronic diseases.
addiction medicine: A medical subspecialty concerned with the prevention, evaluation,

diagnosis, treatment, and recovery of people with the disease of addiction and substance-
related health conditions, as well as people who use substances—including nicotine,
alcohol, prescription medications, and other licit and illicit drugs—in an unhealthy manner
(see addiction, substance use disorder). Addiction medicine is recognized as a distinct
medical subspecialty within preventive medicine by the American Board of Medical
Specialties (ABMS; see addiction specialist physician).
addiction medication: Medications that are specifically indicated for and prescribed to
treat substance use disorders (SUDs) as an initial lifesaving measure, motivational
engagement strategy (ie, withdrawal management), and as part of a long-term treatment
plan similar to medications used to treat other chronic diseases such as bipolar disorder or
diabetes (see substance use disorder).
addiction psychiatry: A psychiatric subspecialty concerned with the evaluation and

treatment of individuals with alcohol, drug, or other substance-related disorders and of
individuals with co-occurring substance-related and other psychiatric disorders (see
addiction, substance use disorder). Addiction psychiatry is recognized as a distinct
medical subspecialty within psychiatry by the American Board of Medical Specialties
(ABMS; see addiction specialist physician).327
addiction specialist physician: A licensed physician who has specialty board certification
in addiction medicine or addiction psychiatry (see addiction medicine, addiction
psychiatry).
adolescent: A person who is 12 to 17 years of age.
cultural humility: A process of entering a relationship with another person with the
intention of honoring their beliefs, customs, and values. It entails an ongoing self-
exploration and self-critique combined with a willingness to learn from others.328 One
component of trauma-sensitive practices (TSP; see trauma-sensitive practices).
drug testing: The process of analyzing a biological specimen to check for the presence of
chemicals that indicate exposure to selected substances.
165
patient: An individual receiving substance use disorder treatment. Interchangeable with

client, which is used more commonly in nonmedical settings.
psychosocial services (as treatment): Interventions that seek to enhance a patient’s social
and mental functioning, including psychotherapy, counseling, contingency management
(CM), psychoeducation, and mental health services.329
recovery: A process of change through which individuals improve their health and
wellness, live a self-directed life, and strive to reach their full potential.330
recovery support services (RSS): The collection of services that provide emotional and
practical support for continuing recovery, as well as daily structure and rewarding
alternatives to substance use (see recovery).331
recurrence: A return of substance use disorder (SUD) symptoms, including substance use,
after a period of remission from SUD (see recovery, substance use disorder).329
social determinants of health (SDOH): The conditions in the environments where people
are born, live, learn, work, play, worship, and age that affect a wide range of health,
functioning, and quality-of-life outcomes and risks.332
substance use disorder (SUD): A medical illness consisting of a cluster of cognitive,

behavioral, and physiological symptoms caused by repeated misuse of a substance or
substances. Characterized by clinically significant impairments in health, social function,
and impaired control over substance use (see addiction).331
substance-induced disorders: Illnesses or conditions that are directly caused by

substance use. Distinct from independently co-occurring mental disorders in that all or
most of the psychiatric signs and symptoms are the direct result of substance use (see
substance use disorder).18
telehealth: The use of electronic information and telecommunications technologies to

support delivery of health care, health-related education, and other health-related services
and functions, including but not limited to electronic health records, mobile applications,
telemedicine, and web-based tools (see telemedicine).333
telemedicine: Services that utilize telecommunication platforms to perform direct

(ie, synchronous) patient services when healthcare providers are located at a distance from
patients (see telehealth).
toxicology testing: Also called toxicology screening, this term refers to the process of
testing for the presence of toxins or poisons (see drug testing).
166
trauma-informed care (TIC): The process of engaging in trauma-based educational

training, including gathering information on the various types of traumas, the physiological
and emotional impact of surviving trauma, and healing modalities to prevent disruptive
aftereffects.
trauma-responsive care (TRC): An ongoing process that furthers trauma-based

education through information embodiment by asking treatment providers to understand
and comprehend information through self-exploration, self-awareness, and reflective
practices to develop a concrete understanding of their own emotional literacy and how this
impacts the care that they provide. One component of trauma-sensitive practices (TSP; see
trauma-sensitive practices).
trauma-sensitive practices (TSP): A system of care that facilitates opportunities that

advance clinician knowledge, expand clinician attitudes, and offer therapeutic practices
designed around each patient’s unique culture, life experiences, and present circumstances.
Comprised of trauma-informed care (TIC), trauma-specific care (TSC), trauma-responsive
care (TRC), and cultural humility (see cultural humility, trauma-informed care, trauma-
responsive care, trauma-specific care)
trauma-specific care (TSC): An ongoing process where treatment providers engage with
trauma knowledge and information to impact, refine, and improve the ways in which
healthcare services are provided to support better patient outcomes. One component of
trauma-sensitive practices (TSP; see trauma-sensitive practices).
warm handoff: A care transition in which the referring clinician facilitates a direct
(ie, face-to-face) introduction of the patient to the receiving clinician at their next level of
care.
young adult: A person who is 18 to 25 years of age.
167
Appendix B. Abbreviations and Acronyms

AAAP American Academy of Addiction Psychiatry
AACAP American Academy of Child and Adolescent Psychiatry
AAFP American Association of Family Physicians
AAP American Academy of Pediatrics
ABMS American Board of Medical Specialties
ACE adverse childhood event
ACEP American College of Emergency Physicians
ACLS advanced cardiac life support
A-CRA adolescent community reinforcement approach
ACS acute coronary syndrome
ADHD attention-deficit/hyperactivity disorder
AMA American Medical Association
APA American Psychiatric Association
ASAM American Society of Addiction Medicine
ATS amphetamine-type stimulant
ATTC Addiction Technology Transfer Center Network
AUD alcohol use disorder
BCR blood urea nitrogen/creatinine ratio
BMI body mass index
BUN blood urea nitrogen
BZD benzodiazepine
CBC complete blood count
CBT cognitive behavioral therapy
CBT4CBT Computer Based Training for Cognitive Behavioral Therapy
CDC US Centers for Disease Control and Prevention
CDC WONDER US Centers for Disease Control and Prevention Wide-ranging Online Data for
Epidemiological Research
CFR US Code of Federal Regulations
CGC Clinical Guideline Committee
CK creatine kinase
168
CLIA Clinical Laboratory Improvement Amendments of 1988

CM contingency management
CMP comprehensive metabolic panel
CMS Centers for Medicare & Medicaid Services
COVID-19 coronavirus disease 2019
CPG clinical practice guideline
CPK creatine phosphokinase
CRA community reinforcement approach
CSSA Cocaine Selective Severity Assessment
C-SSRS Columbia–Suicide Severity Rating Scale
CT computed tomography
d-AMP dextroamphetamine
DEA US Drug Enforcement Administration
DSM Diagnostic and Statistical Manual of Mental Disorders
DSM-5-TR Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision
EBI evidence-based intervention
ECG electrocardiogram
ED emergency department
EEG electroencephalogram
EtD Evidence to Decision
FAVOR Faces & Voices of Recovery
FDA US Food and Drug Administration
FTIR Fourier-transform infrared spectroscopy
GABA gamma-aminobutyric acid
GABA-A gamma-aminobutyric acid A
GRADE Grading of Recommendations Assessment, Development, and Evaluation
HAV hepatitis A virus
HBV hepatitis B virus
HCV hepatitis C virus
HIV human immunodeficiency virus
HUD US Department of Housing and Urban Development
ICD-10 International Classification of Diseases, 10th Revision
169
IM intramuscular
IPV intimate partner violence
IRETA Institute for Research, Education and Training in Addictions
IV intravenous
LDX lisdexamfetamine
LFT liver function test
MAS-ER extended-release mixed amphetamine salts
MATCH Matching Alcoholism Treatments to Client Heterogeneity
MDD major depressive disorder
MDMA 3,4-methylenedioxymethamphetamine
MET motivational enhancement therapy
MI motivational interviewing
MI myocardial infarction
MPH methylphenidate
MSK musculoskeletal
MSM men who have sex with men
NAM National Academy of Medicine
NIDA National Institute on Drug Abuse
NMDA N-methyl-D-aspartate
NMS neuroleptic malignant syndrome
NSDUH National Survey on Drug Use and Health
OCCS Obsessive Compulsive Cocaine Scale
OIG Office of the Inspector General
OROS osmotic-controlled release oral delivery system
OTC over-the-counter
OUD opioid use disorder
PBO phenobarbital
PDMP prescription drug monitoring program
PEP postexposure prophylaxis
PrEP preexposure prophylaxis
Project BETA Best Practices in the Evaluation and Treatment of Agitation
PSS Poisoning Severity Score
170
PTSD post-traumatic stress disorder

QIC ASAM’s Quality Improvement Council
RCT randomized controlled trial
RoB 2 revised Cochrane Risk of Bias tool
ROBINS-I Cochrane Risk of Bias in Non-randomized Studies – of Interventions tool
RSS recovery support services
SAMHSA Substance Abuse and Mental Health Services Administration
SBIRT screening, brief intervention, and referral to treatment
SCS supervised consumption sites
SDOH social determinants of health
SGM sexual and gender minorities
SSP syringe service program
SSSA Stimulant Selective Severity Assessment
STI sexually transmitted infection
StUD stimulant use disorder
SUD substance use disorder
TB tuberculosis
TBI traumatic brain injury
TES Therapeutic Education System
TIP Treatment Improvement Protocol
TUD tobacco use disorder
UNODC United Nations Office on Drugs and Crime
USC Code of Laws of the United States of America
USPSTF US Preventive Services Task Force
VA US Department of Veterans Affairs
WHO World Health Organization
WIC Special Supplemental Nutrition Program for Women, Infants, and Children
YPR Young People in Recovery
171
Appendix C. Differential Diagnosis for

Agitation and Psychosis
The differential diagnosis for agitation and psychosis is very broad. Comprehensive
discussion of this topic is addressed well elsewhere. The following highlights common
conditions to consider in the differential diagnosis of agitation or psychosis in patients with
stimulant intoxication and is not meant to be an exhaustive list. ACEP’s Project BETA
provides a helpful and comprehensive resource.
Indications to perform head CT include:

• altered mental status;
• neurologic symptoms;
• signs of physical trauma (eg, TBI);
• found unconscious or comatose, which can be the result of trauma or stroke,
including stimulant-induced stroke; and
• anoxic injury.
Indications to perform lumbar puncture and blood tests for encephalitis include:
• unexplained fever, and
• meningeal signs and symptoms (eg, stiff neck, photophobia, back pain).
Indications for EEG include:

• seizure not well explained,
• neurologic signs and symptoms not well explained, and
• persistent encephalopathy.
Additional causes of agitation and psychosis include (but are not limited to):
• nutritional deficiencies (eg, Wernicke encephalopathy),
• neurologic disorders (eg, Parkinson’s disease, dementia),
• brain tumors,
• infections,
• endocrine dysfunction,
• thyroid toxicity (eg, thyrotoxicosis),
• hormonal abnormalities (eg, steroid-induced psychosis),
• autoimmune diseases,
• N-methyl-D-aspartate (NMDA) receptor encephalitis, and
• medication reactions that cause neuropsychiatric symptoms.
172
Appendix D. Disclosures of Interest
Clinical Guideline Committee Members

Clinical Guideline Employment Consulting Research Investments and Healthcare-Related Advocacy/
Committee Member Proprietary Interests Organizations Lobbying
Steven L. Baki, MD Department of Veteran None None None None None
Affairs (Attending
Physician); University
of California San
Francisco (Professor)
Dan Ciccarone, MD, MPH University of California Celero Systems (Scientific None None Remedy Alliance (Medical Director) None
San Francisco Advisory Board
(Professor) Member)**; Expert
Witness**
Scott E. Hadland, MD, Massachusetts General None None None American Academy of Pediatrics None
MPH, FASAM Hospital (Chief); (Education)*
Harvard Medical
School (Associate
Professor)
Brian Hurley, MBA, FAPA, County of Los Angeles Centers for Care Innovation None None None None
DFASAM (Medical Director); for the American
Friends Research Psychiatric Association
Institute (Senior (Consulting)
Research Scientist);
Cedar Sinai Health
System (Contracted
Psychiatrist); Private
Practice
Kimberly Kabernagel, DO, Geisinger Marworth None None None None None
FASAM (Medical Director)
Frances R. Levin, MD New York State Major League Baseball Indivior; US World None None None
Psychiatric Institute (Consultant)* Meds; SAMHSA;
(Psychiatrist) NCATS; NIDA
James McKay, PhD University of None None None None None

Pennsylvania
(Professor)
173
Clinical Guideline Employment Consulting Research Investments and Healthcare-Related Advocacy/

Committee Member Proprietary Interests Organizations Lobbying
Larissa Mooney, MD University of California Expert Witness** Aelis Farma** None American Academy of Addiction None
Los Angeles (Professor Psychiatry (President)
of Clinical Psychiatry)
Siddarth Puri, MD Los Angeles County Expert Witness** None None None None
Department of Public
Health (Associate
Medical Director)
Andrew J. Saxon, MD, VA Puget Sound Health Expert Witness** None None UpToDate Inc** (Section Editor) None
FASAM Care System (Director)
Kevin A. Sevarino, MD, Rushford-Hartford None None GlaxoSmithKline (Stockholder)* UpToDate* (Section Author) None
PhD, FASAM Hospital (Psychiatrist)
Kevin Simon, MD Boston Children’s None None None None None

Hospital (Pediatric
Addiction Medicine
Psychiatrist)
Timothy J. Wiegand, MD, University of Rochester None None None None None
FACMT, FAACT, Medical Center
DFASAM (Director, Program
Director)
The above table presents relationships of the Clinical Guideline Committee (CGC) during the past 12 months with industry and other entities that were determined to be relevant to this
document. These relationships are current as of the completion of this document and may not necessarily reflect relationships at the time of this document’s publication. A relationship or
arrangement is considered to be significant if the individual receives compensation which includes cash, shares, and/or anything else of value including direct ownership of shares, stock,
stock options or other interest of 5% more of an entity or valued at $10 000 or more (excluding mutual funds), whichever is greater. A relationship or arrangement is considered to be modest
if it is less than significant under the preceding definition. A relationship or arrangement is considered to be unpaid if the individual does not receive monetary reimbursement. **Indicates
significant relationship. *Indicates modest relationship.
174
ASAM Quality Improvement Council Members

Quality Improvement Salary Consulting Research Investments and Healthcare-Related Advocacy/
Council Member Proprietary Interests Organizations Lobbying
Itai Danovitch, MD, MBA, Cedars-Sinai Medical Expert Witness** None Workit Health (Shareholder)*; Bexson Biomedical* (Board Member); None
DFAPA, DFASAM Center (Chairman of the Science 37 (Shareholder)**; California Mental Health Services
Department of Bexson Biomedical (Receives (Commissioner)
Psychiatry and Equity Options)*
Behavioral
Neurosciences)
Kenneth I. Freedman, MD, Aetna/CVS Health None None None None None
MS, MBA, FACP, AGAF, (Medical Director); The
DFASAM Recovery Research
Network (Medical
Director)
Michael P. Frost, MD, Wayspring (Chief Medical None None Pocket Naloxone Corp Accord Healthcare UK* (Training None
FACP, DFASAM Officer); Frost Medical (Shareholder)** Fees)
Group LLC (Owner)
R. Jeffrey Goldsmith, MD, None None None Merck and Co (Stockholder)*; None None
DLFAPA, DFASAM Pfizer Inc (Stockholder)*;
Amgen Inc (Stockholder)*;
Gilead Sciences Inc
(Stockholder)*
Margaret A. E. Jarvis, MD, Geisinger (Chief, Expert Witness** None None American Board of Preventive None
DFASAM Addiction Medicine Medicine (Exam Committee
Division) Member)
Navdeep Kang, PsyD, HSP Acadia Healthcare (Chief Everest Health (Advisor) None Brightview Health/Shore Capital Talbert House (Board Member) None
Quality Officer) Partners (Equity
Shareholder)**
Tiffany Y. Lu, MD, MS, Montefiore Medical Center None None None None None
FASAM (Staff Physician); ModMed
EHR System
(Spouse/Medical Director)
Tami Mark, PhD, MBA RTI International None None None None None
(Distinguished Fellow
and Director of
Behavioral Health
Financing and Quality
Measurement)
175
Quality Improvement Salary Consulting Research Investments and Healthcare-Related Advocacy/

Council Member Proprietary Interests Organizations Lobbying
Stephen Martin, MD, Boulder Care (Medical None None None None None
FASAM Director); Williamstown
Recovery Operator
(Medical Director)
Melissa B. Weimer, DO, Yale School of Medicine CVS Health None Path CCM, Inc (Stockholder) None None
MCR, DFASAM (Associate Professor, (Consulting)*; Expert
Medical Director, Medical Consulting for
Associate Program Legal Matters**
Director)
The above table presents relationships of ASAM’s Quality Improvement Council during the past 12 months with industry and other entities that were determined to be relevant to this
document. These relationships are current as of the completion of this document and may not necessarily reflect relationships at the time of this document’s publication. A relationship or
arrangement is considered to be significant if the individual receives compensation which includes cash, shares, and/or anything else of value including direct ownership of shares, stock,
stock options or other interest of 5% more of an entity or valued at $10 000 or more (excluding mutual funds), whichever is greater. A relationship or arrangement is considered to be modest
if it is less than significant under the preceding definition. A relationship or arrangement is considered to be unpaid if the individual does not receive monetary reimbursement. **Indicates
significant relationship. *Indicates modest relationship.
176
ASAM Board Members

ASAM Board Member Salary Consulting Research Investments and Healthcare-Related Advocacy/
Proprietary Interests Organizations Lobbying
Brian Hurley, MD, MBA, County of Los Angeles Centers for Care None None None None
FAPA, DFASAM (Medical Director); Friends Innovation for the
Research Institute (Senior American
Research Scientist); Cedar Psychiatric
Sinai Health System Association
(Contracted Psychiatrist); (Consulting)
Private Practice
Stephen M. Taylor, MD, MPH, Pathway Healthcare, LLC Expert Witness None None Medical Review Officer Certification None
DFAPA, DFASAM (Chief Medical Officer); Council (Board Member); Addiction
National Basketball Prevention Coalition (Board
Association/National Member)
Basketball Players
Association (Medical
Director); Private Practice
Aleksandra E. Zgierska, MD, Pennsylvania State University Pennsylvania Medicaid National Institutes None American Academy of Pain Medicine* None
PhD, DFASAM (Associate Director) (Single-Time of Health/ (Substance Use Disorder Shared
Advisor)* National Institute Interest Group Co-Chair)
on Drug Abuse*
Anika Alvanzo, MD, MS, Uzima Consulting Group, Triple Track Treatment None None None None
FACP, DFASAM LLC (Managing Partner); (Potential
Pyramid Healthcare, Inc Consultant);
(Regional Medical Behavioral
Director) Administration,
Maryland
Department of
Health (Consultant)*
Timothy J. Wiegand, MD, University of Rochester None None None None None
FACMT, FAACT, Medical Center (Director,
DFASAM Program Director)
William F. Haning, III, MD, None (retired) None None None None None
DLFAPA, DFASAM
Kelly S. Ramsey, MD, MPH, Office of Addiction Services None None None New York Society of Addiction None
MA, FACP, DFASAM and Supports (OASAS) Medicine (Board Member)
Itai Danovitch, MD, MBA, Cedars-Sinai Medical Center Expert Witness** None Workit Health (Shareholder)*; Bexson Biomedical* (Board Member); None
DFAPA, DFASAM Science 37 (Shareholder)**; California Mental Health Services
Bexson Biomedical (Commissioner)
(Receives Equity Options)*
177
Audrey M. Kern, MD, Pear Therapeutics, Sobriety None None None New Hampshire Healthy Families* None
DFASAM Centers of New Hampshire (Board Member)
Shawn Ryan, MD, MBA, BrightView Health (Owner) Dynamicare (Advisor) None Dynamicare (Shareholder) None None
FASAM
Megan Buresh, MD, Johns Hopkins School of None National Institutes None Association of Medical Education and None
Medicine (Assistant on Drug Abuse* Research in Substance Abuse (2023-
DFASAM Professor); Behavioral 2024 Conference Planning Co-
Health Leadership Institute Chair); American Journal of
(Lead Physician) Medicine Open* (Associate Editor)
Emily Brunner, MD, Hazelden Betty Ford None None None None None
DFASAM Foundation, Gateway
Recovery Center
Christina E. Jones, MD, Teleleaf, LLC (Provider) None None None None None
FASAM
Teresa Jackson, MD, Lakeside Milam Recovery None None None National Association of Addiction None
DFASAM Centers (Medical Director) Treatment Providers (Clinical and
Reimbursement Committee Member)
Keyghobad Farid Araki, MD, Centre for Addiction and None None None None None
FRCPC, ABAM, FASAM Mental Health (Psychiatrist
and Addiction Specialist)
James P. Murphy, MD, Kentucky Harm Reduction None None None None None
DFASAM Coalition (Co-Director);
Private Practice
Alta DeRoo, MD, MBA, Hazelden Betty Ford None None None None None
FACOG, DFASAM Foundation (Chief Medical
Officer)
Marla D. Kushner, DO, Bicycle Health (Regional None None None American Osteopathic Academy of None
FACOFP, FAOAAM, Medical Director) Addiction Medicine*
FSAHM, DFASAM
Lori D. Karan, MD, FACP, Loma Linda University Expert Witness*; John None None American College of Addiction None
DFASAM Medical School (Director, A. Burns School of Medicine (Immediate Past President)
Professor); VA Loma Medicine (Presenter)
Linda Healthcare System
(Employee)
Nicole Labor, DO, FASAM Esper Treatment Center; IBH None None None None None
Addiction Recovery; One-
Eighty (Medical Director)
178
Surita Rao, MD, FASAM University of Connecticut None None None None None
Medical School (Associate
Professor)
Michael F. Weaver, MD, University of Texas Health None None None American Board of Preventive None
DFASAM Science Center at Houston Medicine (Board Member)
(Professor, Director)
Michael Fingerhood, MD, Johns Hopkins University None None None American Academy of HIV Medicine None
FACP, DFASAM (Associate Professor); (Board Member)
Johns Hopkins Bayview
Medical Center (Chief of
the Division of Addiction
Medicine)
Kenneth I. Freedman, MD, Aetna/CVS Health (Medical None None None None None
MS, MBA, FACP, AGAF, Director); The Recovery
DFASAM Research Network
(Medical Director)
Margaret A. E. Jarvis, MD, Geisinger (Chief of Addiction Expert Witness** None None American Board of Preventive None
DFASAM Medicine Division) Medicine (Exam Committee
Member)
Nicholas Athanasiou, MD, Los Angeles County None None None American Board of Psychiatry and None
MBA, DFASAM Department of Mental Neurology (Past Addiction
Health (Provider); Private Psychiatry Committee Member)
Practice
Cara A. Poland, MD, MEd, Michigan State University None None None None None
FACP, DFASAM Department of Obstetrics
and Gynecology (Faculty)
The above table presents relationships of ASAM’s Board of Directors during the past 12 months with industry and other entities that were determined to be relevant to this document. These
relationships are current as of the completion of this document and may not necessarily reflect relationships at the time of this document’s publication.
179
AAAP Executive Committee

AAAP Executive Salary Consulting Research Investments and Proprietary Healthcare-Related Advocacy/
Committee Interests Organizations Lobbying
Karen Drexler, MD American Academy of None None None None None
Addiction Psychiatry
(Medical Director)
Tim Fong, MD University of California None None None None None
Los Angeles (Clinical
Professor of Psychiatry)
Kevin Gray, MD Medical University of Jazz Pharmaceuticals Aelis Farma None None None
South Carolina (Consulting)
(Professor and Director
of Addiction Sciences)
Shelly F. Greenfield, MD, Harvard Medical School None None None None None
MPH (Professor of Psychiatry)
John Mariani, MD Columbia University, New None None None None None
York State Psychiatric
Institute (Directors of
STARS)
Larissa Mooney, MD University of California Expert Witness Aelis Farma None American Academy of Addiction None
Los Angeles (Professor Psychiatry (President)
of Clinical Psychiatry)
Rebecca Payne, MD University of South None None None None None
Carolina (Assistant
professor of
Neuropsychiatry and
Behavioral Science)
Kevin Sevarino, MD, PhD Rushford-Hartford Hospital None None GlaxoSmithKline (Stockholder) UptoDate* (Section Author) None
(Psychiatrist)
Carol Weiss, MD Weill Cornel Medical None None None None None
College (Clinical
Associate Professor of
Psychiatry)
The above table presents relationships of AAAP’s Executive Committee members during the past 12 months with industry and other entities that were determined to be relevant to this
document. These relationships are current as of the completion of this document and may not necessarily reflect relationships at the time of this document’s publication.
180
Appendix E. Clinical Questions

This appendix presents the clinical questions posed for each topic as outlined in the
supplementary EtD document. If a clinical question resulted in a recommendation based
only on clinical consensus, there is no corresponding table in the EtD document.
Treatment of Stimulant Use Disorder

Assessment
1. Initial assessment:
a. What components should be included in the initial assessment for patients
presenting with StUD?
2. Comprehensive assessment:
a. What components should be included in the comprehensive assessment for
patients with StUD?
3. Baseline laboratory testing:
a. Should baseline laboratory testing be conducted for all patients with StUD or
based on clinical assessment of risk factors?
b. What is the effect of conducting baseline laboratory testing when assessing
patients with StUD?
c. What contextual factors and implementation strategies may influence the effects
of baseline laboratory testing?
d. What are the most impactful and appropriate baseline laboratory tests to
conduct when assessing patients who misuse use stimulants?
4. Cardiac evaluation:
a. Should clinicians routinely request or refer patients for a cardiac evaluation or
ECG?
i. Patients with stimulant intoxication or withdrawal
ii. Patients with StUD
b. What is the effect of routine screening for cardiac disorders in patients with
StUD?
181
of screening for cardiac disorders?
d. Is there a subpopulation that would particularly benefit from routine ECG?
5. Renal evaluation:
a. For patients diagnosed with stimulant intoxication or withdrawal, should
clinicians routinely request or refer patients for an evaluation of renal function?
b. For patients diagnosed with StUD, should clinicians routinely request or refer
patients for an evaluation of renal function?
c. Is there a subpopulation who would benefit from an evaluation of renal
function?
Behavioral Treatment
1. Contingency Management (Table 1):
a. Is CM an effective and appropriate treatment for StUD?
b. Does the addition of another treatment to CM improve outcomes for StUD?
of CM?
2. Community Reinforcement Approach (Table 2):
a. Is CRA (with or without background treatment) an effective and appropriate
treatment for StUD?
b. Is CRA more effective than other behavioral treatments for StUD?
c. Does adding CM to CRA improve outcomes for StUD?
d. What additional considerations and implementation strategies may influence the
effects of CRA?
3. Cognitive Behavioral Therapy (Table 3):
a. Is CBT (with or without background treatment) effective at reducing stimulant
use and increasing treatment retention in patients in treatment for StUD?
b. Is CBT more effective than other behavioral treatments for StUD?
c. Does adding CM to CBT improve outcomes for StUD?
effects of CBT?
182
4. Matrix Model (Table 4):

a. Is the Matrix Model an effective and appropriate treatment for StUD?
b. Is the Matrix Model more effective than other behavioral treatments for StUD?
c. Does adding CM to the Matrix Model improve outcomes for StUD?
effects of the Matrix Model?
Technology-Based Interventions
1. Computer-Delivered Treatment (Table 5):
a. What is the effect of computer-delivered treatment for StUD?
b. What contextual factors and implementation strategies may influence the effects
of computer-delivered treatment?
2. Telehealth (Table 6):
a. What is the effect of telehealth-delivered treatment for StUD?
of telehealth-delivered treatment?
Pharmacotherapy
1. Bupropion for Cocaine Use Disorder (Table 7):
a. Is bupropion safe and effective at reducing stimulant use and increasing
treatment retention in patients with cocaine use disorder?
2. Topiramate for Cocaine Use Disorder (Table 8):
a. Is topiramate safe and effective at reducing stimulant use and increasing
treatment retention in patients with cocaine use disorder?
3. Bupropion for Amphetamine-Type Stimulant Use Disorder (Table 9):
a. Is bupropion safe and effective at reducing stimulant use and increasing
treatment retention in patients with ATS use disorder?
4. Bupropion + Naltrexone for Amphetamine-Type Stimulant Use Disorder (Table 10):
a. Is the combination pharmacotherapy of bupropion and naltrexone safe and
effective at reducing stimulant use and increasing treatment retention in
patients with ATS use disorder?
183
of bupropion + naltrexone?
5. Topiramate for Amphetamine-Type Stimulant Use Disorder (Table 11):
a. Is topiramate safe and effective at reducing stimulant use and increasing
treatment retention in patients with ATS use disorder?
6. Mirtazapine for Amphetamine-Type Stimulant Use Disorder (Table 12):
a. Is mirtazapine a safe and effective treatment for ATS use disorder?
7. Modafinil for Cocaine Use Disorder (Table 13):
a. Is modafinil a safe and effective treatment for patients with cocaine use
disorder?
8. Topiramate + Extended-Release Mixed Amphetamine Salts for Cocaine Use Disorder
(Table 14):
a. Is the combination pharmacotherapy of topiramate and MAS-ER safe and
effective treatment for patients with cocaine use disorder?
of topiramate + MAS-ER?
9. Psychostimulant Amphetamines for Cocaine Use Disorder (Table 15):
a. Are long-acting amphetamine formulations of prescription psychostimulants
safe and effective at reducing stimulant use and increasing treatment retention
in patients with cocaine use disorder?
10. Psychostimulant Methylphenidate for Amphetamine-Type Stimulant Use Disorder
(Table 16):
a. Are long-acting MPH formulations or prescription psychostimulants safe and
effective at reducing stimulant use and increasing treatment retention in
patients with ATS use disorder?
1. Integrated Care (Table 17):
a. What are the most effective and appropriate behavioral interventions for the
treatment of StUD in patients with co-occurring psychiatric disorders?
of behavioral interventions?
184
2. Psychosis (Table 18):

a. Should clinicians use pharmacotherapy to treat psychosis or mania if it is
unclear whether the condition is preexisting or stimulant-induced?
b. What contextual factors and implementation strategies may influence the
decision to use pharmacotherapy?
c. What are the most effective and appropriate interventions for treating psychosis
in patients with StUD?
3. Psychosis taper (Table 19):
a. What is the optimal duration of antipsychotic treatment for persons who are
presumed to be experiencing stimulant-induced psychosis or mania?
b. What is the clinical effectiveness of different antipsychotic tapering strategies?
4. Other Symptoms (Table 20):
a. Should clinicians use pharmacotherapy to treat depression, anxiety, insomnia,
and/or attentional problems in patients with StUD if it is unclear whether the
condition is preexisting or stimulant-induced?
decision to use pharmacotherapy?
c. What are the most effective and appropriate pharmacotherapies for treating
depression, anxiety, insomnia, and/or attentional problems in patients with
StUD?
5. Preexisting diagnosis:
a. Should patients change or discontinue treatment for a co-occurring disorder
when initiating treatment for StUD?
decision to modify the existing treatment plan?
6. Attention-Deficit/Hyperactivity Disorder (Table 21):
a. What are the most effective and appropriate interventions to treat ADHD in
patients with StUD?
b. Are stimulant medications safe and effective to treat ADHD in patients with
StUD?
c. What contextual factors and implementation strategies may influence the safety
and effectiveness of ADHD treatment?
185
7. Prevention of prescription stimulant misuse:

a. When prescribing stimulant medications to a patient with co-occurring StUD and
ADHD, what implementation strategies may influence the effect and
appropriateness of treatment?
8. Prevention of prescription stimulant misuse in adolescents and young adults:
a. When prescribing stimulant medications to an adolescent or young adult patient
with co-occurring StUD and ADHD, what implementation strategies may
influence the effect and appropriateness of treatment?

1. Toxicology:
a. What is the most effective and appropriate use of toxicology testing for the
treatment of StUD, stimulant intoxication, and stimulant withdrawal in
adolescent and young adult patients?
of toxicology testing?
2. Screening – other:
a. What is the effect of screening for other co-occurring conditions when assessing
adolescent and young adult patients for StUD?
i. StUD outcomes
ii. Other outcomes
of screening for other co-occurring conditions?
3. Specific support:
a. Should adolescent patients be referred to adolescent-specific support services or
are adult services effective and appropriate?
b. Do young adult-specific social supports services exist?
c. What contextual factors and implementation strategies may influence the
effectiveness of a support service referral?
4. Contingency Management (Table 22):
a. Is CM for patients with StUD as effective and appropriate for adolescents and
young adults as it is for adults?
186
of CM for adolescents and young adults?
c. What modifications should be made so that CM is delivered in a developmentally
appropriate manner?
5. Other Psychotherapy (Table 23):
a. What are the most effective and appropriate psychotherapy interventions for the
treatment of StUD in adolescent and young adult patients?
of psychotherapy interventions?
6. Family Therapy (Table 24):
a. Is family therapy effective in treating adolescents and young adults with StUD?
of family therapy?
7. Specific Treatment (Table 25):
a. Are adolescent-specific behavioral treatment models (eg, A-CRA) effective and
appropriate treatment for StUD in adolescents and young adults?
b. Should adolescents be referred to adolescent-specific behavioral treatment
models (eg, A-CRA) or are adult treatment models effective and appropriate?
c. What modifications should be made so that behavioral treatment is delivered in
a developmentally appropriate manner?
8. Group Treatment (Table 26):
a. Are there modifications that should be made to behavioral treatment so that it is
delivered in a developmentally appropriate manner to adolescent and young
adult patients?
b. Should adolescents and young adults who use stimulants be referred to
adolescent- and young adult-specific group-based treatment or is adult group-
based treatment as effective and appropriate?
9. Pharmacotherapy (Table 27):
a. What are the most effective and appropriate pharmacotherapies for the
treatment of StUD in adolescent and young adult patients?
of pharmacotherapy?
10. Home drug testing:
a. What are the potential benefits and harms of home drug testing?
187
11. Family involvement:

a. Are there modifications that should be made to behavioral treatment so that it is
delivered in a developmentally appropriate manner to adolescent and young
adult patients?
b. Is family involvement in the treatment of StUD in adolescent and young adult
patients effective and appropriate?
12. Minor consent:
a. What considerations should be included regarding consent for treatment for
minor patients?
Pregnant and Postpartum Patients

1. Prenatal Care Referral (Table 28):
a. What additional considerations should clinicians have when evaluating StUD in
persons who are pregnant?
b. What additional considerations should be included when establishing a
treatment plan for StUD in persons who are pregnant?
2. Screen Social Services – Pregnancy and Postpartum (Table 29):
a. Are there additional social service needs that should be addressed when
assessing persons who are pregnant or is the standard assessment for StUD
appropriate and effective?
3. Screen Factors Pregnancy (Table 30):
a. Are there additional health conditions that should be evaluated in persons who
are pregnant or is the standard assessment for StUD appropriate and effective?
4. Toxicology – pregnancy and postpartum:
a. Are there additional considerations when conducting toxicology testing in
persons who are pregnant or are standard considerations for StUD appropriate
and effective?
5. Pharmacotherapy – Pregnancy and Postpartum (Table 31):
a. What additional considerations should be included when considering
pharmacotherapy for StUD, stimulant intoxication, or stimulant withdrawal in
persons who are pregnant or breastfeeding?
6. Psychosocial additions – pregnancy and postpartum:
a. Are there additional treatment needs that should be addressed with pregnant
patients or is standard treatment for StUD appropriate and effective?
188
7. Prenatal Care Incentives (Table 32):

a. What are the most effective and appropriate interventions for increasing
prenatal care access and attendance in patients being treated for StUD?
8. Postpartum Care (Table 33):
a. Are there additional treatment needs for patients with StUD in the postpartum
period? For patients with any level of stimulant use?
9. Breastfeeding (Table 34):
a. Should patients with StUD breastfeed?
b. When can a patient who uses stimulants safely breastfeed?
c. Can clinicians increase the rate of safe breastfeeding in patients with a StUD?
With any stimulant use?
Additional Population-Specific Considerations

1. Sexual and Gender Minoritized individuals (Table 35):
a. What are the most effective and appropriate interventions for the treatment of
StUD in SGM patients?
b. Should SGM patients with StUD be referred to SGM-focused programs?
c. What additional consideration should clinicians have when evaluating and
treating StUD in SGM patients?
2. Disability:
StUD in patients with disabilities?
b. What additional considerations should clinicians have when evaluating and
treating StUD in persons with disabilities?
3. Criminal/legal system:
StUD in patients with criminal/legal system involvement?
b. What additional considerations should clinicians have when evaluating and
treating StUD in patients with criminal/legal system involvement?
4. Homelessness/unstable housing:
StUD in patients with unstable housing or who are experiencing homelessness?
189
b. Should patients with unstable housing or who are experiencing homelessness be

referred specialized StUD programs or is general StUD treatment effective and
appropriate?
c. What additional considerations should clinicians have when evaluating and
treating StUD in persons with unstable housing or who are experiencing
homelessness?

Assessment and Diagnosis
1. Initial assessment – intoxication and withdrawal:
a. For patients with suspected stimulant intoxication or withdrawal, should an
initial assessment for acute issues and complications related to stimulant
intoxication and withdrawal be part of routine assessment or only as needed?
b. What is the appropriate medical workup when evaluating a patient with
suspected stimulant intoxication or withdrawal?
2. Comprehensive assessment – intoxication and withdrawal:
a. For patients with a diagnosis of stimulant intoxication or withdrawal, should
comprehensive assessment for acute issues and complications related to
stimulant intoxication and withdrawal be part of routine assessment or only as
needed?
b. What is the appropriate medical workup when evaluating a patient with
stimulant intoxication or withdrawal?
c. Should laboratory testing be ordered (or a referral for testing be provided)
routinely or as needed according to clinical judgment and based on
symptomatology and presence of risk factors?
3. Baseline laboratory testing – intoxication and withdrawal:
a. Should laboratory testing be ordered (or a referral for testing be provided) for
all patients with stimulant intoxication or withdrawal or based on clinical
assessment of risk factors?
patients?
190
d. What are the most appropriate baseline laboratory tests to conduct when
assessing patients who use stimulants?
4. Intoxication toxicology:
a. For patients with suspected stimulant intoxication or withdrawal, should
toxicology testing for stimulants be a routine part of diagnostics?
i. Does this depend on the setting?
b. If toxicology testing is done as needed, what are the indications?
5. Intoxication setting:
a. In what setting should patients with stimulant intoxication and withdrawal be
managed?
b. Can suspected stimulant intoxication be managed safely in lower acuity clinical
settings?
c. Which patients with stimulant intoxication be managed safely in lower acuity
clinical settings?
Managing Stimulant Intoxication and Withdrawal

1. Agitation–psychosis differential diagnosis:
2. What are indications of different or additional causes of agitation and psychosis?
3. Agitation–psychosis de-escalation:
4. What is the effectiveness of de-escalation techniques for managing stimulant-induced
aggression, agitation, or toxic psychosis?
5. Agitation Medication (Table 36):
agitation in patients experiencing stimulant intoxication?
of the intervention for agitation?
6. Psychosis Medication (Table 37):
psychosis in patients experiencing stimulant intoxication?
b. Should clinicians treat stimulant-induced psychotic symptoms with
antipsychotics?
7. Agitation–psychosis evaluation:
191
a. What are the indications for an immediate need for acute care management in a
hospital or ED?
8. Agitation–psychosis transfer:
a. What factors should be considered when determining whether to transfer a
patient presenting with agitation or psychosis to a more intensive level of care?
9. Psychiatric monitoring:
a. What are the most effective and appropriate strategies to monitor psychiatric
symptoms when treating patients experiencing stimulant intoxication or
withdrawal?
b. For patients diagnosed with stimulant intoxication or withdrawal, should
clinicians routinely assess for trauma-related problems or only as needed?
c. What should the frequency of reassessment be during monitoring?
10. Hyperadrenergic monitoring: No clinical questions in the EtD document.
a. What are the most effective and appropriate strategies to monitor
hyperadrenergic signs and symptoms when treating patients experiencing
stimulant intoxication or withdrawal?
b. What should the frequency of reassessment be during monitoring?
11. Hyperadrenergic Medications (Table 38):
hyperadrenergic symptoms that typically accompany stimulant intoxication?
12. Hyperadrenergic Adjunct (Table 39):
a. What adjunctive treatments can be considered for managing hyperadrenergic
symptoms that typically accompany stimulant intoxication?
13. Hypertensive Emergency (Table 40):
a. What are effective interventions for hypertensive emergency accompanying
stimulant intoxication?
14. Chest Pain Medication (Table 41):
chest pain in patients experiencing stimulant intoxication?
15. Chest Pain Beta Blockers (Table 42):
a. What is the effectiveness of beta blockers for managing the cardiac
consequences of stimulant intoxication?
b. Can beta blockers be used safely to treat chest pain in patients experiencing
stimulant intoxication?
192
16. Chest Pain Evaluation (Table 43):

a. Should the presence of stimulant intoxication impact the standard evaluation of
chest pain?
17. QRS Widening (Table 44):
QRS widening following cocaine use?
18. Seizure workup:
a. Should a full neurological workup be ordered for all patients presenting to the
ED with a seizure following stimulant use?
19. Seizure Medication (Table 45):
seizure following stimulant use?
20. Screening, Brief Intervention, and Referral to Treatment (SBIRT; Table 46):
a. How accurate are drug use screening instruments for risky stimulant use?
b. Does screening for stimulant use reduce stimulant use or improve other risky
behaviors?
c. What are the harms of screening for risky stimulant use?
d. Do brief counseling interventions to reduce stimulant use, with or without
referral, reduce stimulant use or improve other risky behaviors in patients with
a positive screen?
e. What are the harms of brief interventions to reduce stimulant use in patients
with a positive screen?
Secondary and Tertiary Prevention

Screening
1. Screening for Stimulants (Table 47):
a. How accurate are drug use screening instruments for risky stimulant use?
b. Does screening for stimulant use reduce stimulant use or improve other risky
behaviors?
c. What are the harms of screening for risky stimulant use?
193
2. Screening for Prescription Psychostimulants (Table 48):

a. What additional considerations should be applied when screening for
prescription psychostimulant misuse?
3. Check Prescription Drug Monitoring Program (Table 49):
a. What are the benefits and harms of checking PDMPs for patients with StUD?
Assessment
1. Assessing Route Complications – Prevention (Table 50):
a. What are effective strategies for assessing route of administration and related
history of complications?
2. Assessing Risky Patterns – Prevention (Table 51):
a. What are effective strategies for assessing risky patterns of stimulant use?
3. Assessing Risky Sex – Prevention (Table 52):
a. What are effective strategies for assessing risky sexual behaviors in patients
with SUD/StUD?
4. Assessing context of stimulant use – prevention:
a. What are effective strategies for assessing the context of a patient’s stimulant
use?
5. Assessing trauma – prevention:
a. What are effective strategies for assessing trauma in patients with SUD/StUD?
6. Assessing baseline laboratory testing – prevention:
a. What are the most effective and appropriate baseline laboratory tests to conduct
when assessing patients who misuse or use stimulants?
patients who misuse stimulants?
i. For StUD outcomes
ii. For other outcomes
c. Should baseline laboratory testing be conducted for all patients who misuse or
use stimulants or based on clinical assessment of risk factors?
d. What contextual factors and implementation strategies may influence the effects
194
7. Assessing ADHD – prevention:

a. Should all patients who misuse or use stimulants be assessed for ADHD?
b. What factors should be considered when determining which patients to assess
for ADHD?
Early Intervention for Risky Stimulant Use

1. Early Intervention – Screening and Brief Intervention (Table 53):
a. Do brief counseling interventions to reduce stimulant use, with or without
referral, reduce stimulant use or improve other risky behaviors in patients with
a positive screen?
b. What are the harms of brief interventions to reduce stimulant use in patients
with a positive screen?
2. Early Intervention Refer to Treatment (Table 54):
a. Does referral to treatment reduce stimulant use or improve risky behaviors in
patients with a positive screen?
b. What are effective strategies for referral to treatment for StUD?
3. Early Intervention Peer Navigation (Table 55):
a. Does peer navigation improve referral for treatment in patients with a positive
screen?
Harm Reduction
1. Education Stimulants (Table 56):
a. What are effective educational strategies for reducing harms related to stimulant
use or StUD-related behaviors?
2. Prevention – Refer to Harm Reduction (Table 57):
a. Does referral for harm reduction services reduce harms related to stimulant use
or StUD-related behaviors?
3. Education – Overdose (Table 58):
a. What are effective strategies for preventing overdose in patients with StUD?
4. Education – Sex (Table 59):
a. What are effective strategies for preventing risky sex-related harms in patients
with StUD?
195
5. Prevention – Condoms:
a. What are effective strategies for increasing condom use in patients with StUD?
6. Prevention – Routine Sexually Transmitted Infection Testing:
a. How often should STI testing be conducted in patients with StUD and other
StUD-related risk factors?
7. Prevention – Naloxone (Table 60):
a. What are effective strategies for distributing naloxone to patients with StUD?
8. Prevention – Drug Checking (Table 61):
a. Is drug checking an effective strategy for reducing harms related to StUD?
9. Prevention – Supervised Consumption (Table 62):
a. Is referral to SCS effective for reducing harms related to StUD?
10. Prevention – Routine Sexually Transmitted Infection Testing (Table 63):
a. How often should STI testing be conducted in patients with StUD and other
StUD-related risk factors?
11. Education – Injection Drug Use (Table 64):
a. What educational interventions are effective for reducing harms related to
injection drug use?
12. Prevention – Injection Drug Use Kits (Table 65):
a. Are injection drug use kits effective for reducing harms related to injection drug
use?
13. Prevention – HIV Preexposure Prophylaxis (PrEP) (Table 66):
a. What factors should be considered when determining the appropriateness of
HIV PrEP for patients with StUD?
14. Prevention – Oral Health (Table 67):
a. What interventions are effective for preventing oral health-related harms in
patients with StUD?
15. Prevention – Nutrition:
a. What interventions are effective for preventing nutrition-related harms in
patients with StUD?
196
Appendix F. Topics with Insufficient or

Negative Evidence
The following table presents interventions for which the evidence considered by the CGC
was determined to be insufficient or not supportive.
Intervention Type Intervention
Technology-based interventions Text messaging interventions for StUD
Technology-based interventions Noninvasive brain stimulation for StUD
Alternative interventions Exercise as standalone or add-on treatment for StUD
Alternative interventions Auricular acupuncture for ATS use disorder
Pharmacotherapy Topiramate and mixed amphetamine salts for ATS use

disorder
Pharmacotherapy Bupropion and naltrexone for cocaine use disorder
Pharmacotherapy Modafinil for ATS use disorder
Pharmacotherapy Mirtazapine for cocaine use disorder
Pharmacotherapy Disulfiram
Pharmacotherapy Naltrexone
Pharmacotherapy Naltrexone and N-acetylcysteine
ATS, amphetamine-type stimulants; StUD, stimulant use disorder
197
Appendix G. Additional Resources
Stimulant Use Disorder: General Information and

Guidelines
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Practice Guideline for the Management of Substance Use Disorders. Management of
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Screening
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Substance-Use-Disorders/SMA12-4079
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Transgender, Queer, and Intersex (LGBTQI+) Resources. SAMHSA. Updated April 24, 2023.
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Substance Abuse and Mental Health Services Administration. A Provider’s Introduction to

Substance Abuse Treatment for Lesbian, Gay, Bisexual, and Transgender Individuals. SMA12-
4104. SAMHSA; 2012. https://store.samhsa.gov/product/Providers-Introduction-
Substance-Abuse-Treatment-Lesbian-Gay-Bisexual-Transgender/SMA12-4104
Thorne Harbour Health. Policy and Practice Recommendations: for alcohol and other drugs
(AOD) Service providers supporting the Trans and Gender Diverse (TGD) community. VAC/
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University of Melbourne. Building sensitivity to LGBT clients accessing alcohol and drug
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207
Sleep
Sleep problems-Insomnia Management Kit. Drug and Alcohol Services South Australia
(DASSA). Accessed May 6, 2022.
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Services/Mental+Health+and+Drug+and+Alcohol+Services/Drug+and+Alcohol+Services/F
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Substance Abuse and Mental Health Services Administration. Treating Sleep Problems of
People in Recovery From Substance Use Disorders. SMA14-4859. SAMHSA; 2014.
https://store.samhsa.gov/product/Treating-Sleep-Problems-of-People-in-Recovery-From-
Substance-Use-Disorders/SMA14-4859
Suicide
The Suicide Prevention Resource Center. Accessed June 27, 2023. https://sprc.org/
Substance Abuse and Mental Health Services. 988 Suicide and Crisis Lifeline. SAMHSA.
Updated April 24, 2023. Accessed June 27, 2023. https://www.samhsa.gov/find-help/988
Substance Abuse and Mental Health Services Administration. Suicide Assessment Five-step
Evaluation and Triage (SAFE-T). SMA09-4432. SAMHSA;2009.
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Trauma-Informed Care
Centers for Disease Control and Prevention. Sexual Violence. CDC; 2022.
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Centers for Disease Control and Prevention. Sexual Violence Resources. CDC; 2022.
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doi:10.1001/jama.2018.14741
Substance Abuse and Mental Health Services Administration. TIP 57: Trauma-Informed
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Informed-Care-in-Behavioral-Health-Services/ SMA14-4816).
208
Substance Abuse and Mental Health Services Administration. SAMHSA’s Concept of Trauma
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https://store.samhsa.gov/product/SAMHSA-s-Concept-of-Trauma-and-Guidance-for-a-
Trauma-Informed-Approach/SMA14-4884
US Department of Veterans Affairs. PTSD: National Center for PTSD. VA;2023.

https://www.ptsd. va.gov/professional/index.asp
Violence
National Institute for Health and Care Excellence. Violence and Aggression: Short-Term
Management in Mental Health, Health and Community Settings. Guideline NG10. National
Institute for Health and Care Excellence (NICE); 2015.
209
Appendix H. Substance Use Disorder

Biopsychosocial Assessment
specific to StUD or of increased importance in the treatment of this illness. However, it is
important for clinicians to deliver the full standard of care that should be provided to any
patient with SUD, including a full biopsychosocial assessment that evaluates:
• substance use-related risks (eg, risks associated with current patterns of substance
use);
• social and environmental factors, including SDOH, that may impact access to or
efficacy of care, such as housing, transportation, and childcare needs, among others;
• trauma-related concerns using trauma-sensitive screening practices;
• biomedical comorbidities;
• post-acute symptoms of withdrawal;
• psychiatric comorbidities and psychiatric disorder history;
• risk factors for infectious diseases, such as HIV and viral hepatitis (eg, HAV, HBV,
HCV), including:
o sexual practice history to screen for risky sexual behaviors in accordance
with current guidance,
 When taking a sexual history and addressing risk factors for STI,
clinicians should pay particular attention to patient comfort, seek
to maximize rapport, and be responsive to the patient's readiness
to discuss their sexual practices.
o injection drug use, and
o sharing drug preparation supplies;
• co-occurring behavioral addictions and/or compulsions (eg, gambling disorder,
internet use, gaming, sex);
• family and/or household substance use, SUDs, and psychiatric histories; and
• contraceptive practices and related needs.
210
Appendix I. Baseline Laboratory Testing

specific to StUD or of increased importance in the treatment of this illness. However, it is
important for clinicians to deliver the full standard of care that should be provided to any
patient with SUD, including routinely ordering baseline laboratory testing for patients with
a newly diagnosed SUD or psychiatric disorder.
In non-acute care settings, clinicians should order the following clinical tests for most
patients:
• CBC,
• CMP (eg, renal panel, LFTs),
• screening for infectious diseases in accordance with current guidance,
• HIV and HCV for all patients,
• HBV for patients at increased risk for infection,
• screening for STIs (eg, gonorrhea, chlamydia, syphilis), and
• pregnancy testing for all patients with childbearing potential.
Clinicians can also consider ordering the following clinical tests:

• tuberculosis (TB) for patients at increased risk for infection;
• HAV for patients at increased risk for infection; and
• other clinical tests as necessary based on clinical assessment, such as CK if signs of
rhabdomyolysis are present (eg, increased muscle tone/rigidity, elevated
temperature).
211
Appendix J. Principles of Drug Testing During

Withdrawal Management
This appendix outlines the major principles in ASAM’s Appropriate Use of Drug Testing in
Clinical Addiction Medicine consensus statement. For additional guidance, please refer to
the full statement.
1. Drug testing can be used to help inform clinical decision-making for patients with SUD
or at risk for substance withdrawal.
2. Drug testing can neither diagnose nor rule out SUD.
3. Drug test results should be used in combination with patient history, physical exam,
and psychosocial assessment to determine the patient’s care plan.
4. Drug testing can be an important supplement to patient self-report because patients
may not be aware of the composition of the substances they have used.
5. Drug test selection should be individualized based on specific patients and clinical
scenarios. Before choosing the type of test and matrix, the clinician should determine
the questions they are seeking to answer and consider the benefits and limitations of
each test and matrix (eg, urine, blood, saliva, hair). The methods used will impact
interpretation of the results:
a. Each matrix has advantages and disadvantages (eg, ease of collection, window of
detection, susceptibility to tampering).
b. Tests are designed to measure if specific substances have been used within
particular windows of time.
c. Selection of a drug testing panel should be based on the patient’s self-reported
use, prescribed medications, and substances commonly used in the geographic
area and by the patient’s peer group.
i. Note that many drug test panels do not detect fentanyl and fentanyl
analogs.
d. It is important to understand the difference between presumptive drug tests,
which are routinely used for point-of-care testing, versus definitive tests, which
are used to confirm the results of presumptive tests and rule out false positives.
i. Definitive testing is done by CLIA-certified laboratories.
6. Definitive testing should be used when the results inform clinical decisions with major
clinical or nonclinical implications for the patient (eg, changes in medications or legal
status).
212
7. Drug test results should be interpreted by a clinician whose scope of practice includes
ordering drug tests and interpreting drug test results and who will consider the
limitations of the specific test used.
8. Discrepancies between patient self-report and drug tests should be discussed with the
patient.
9. Clinicians should keep drug test results confidential to the extent permitted by law.
10. Providers should be aware of the adverse legal and social consequences of detecting
substance use via drug testing in pregnant patients. The patient should be made aware
of local and state reporting requirements before drug tests are conducted.
213
Appendix K. Medication Dosing in Clinical

Trials
This appendix presents a summary of dosing strategies used in the clinical trials reviewed,
but is not intended as a dosing guide.
Table 1. Medication Dosing: Psychostimulant
Study Drug Dose SUD
Modafinil
Anderson et al, 2009334 Modafinil 200 mg or Cocaine

400 mg/day
Anderson et al, 2012335 Modafinil 200 mg or Cocaine, ATS

400 mg/day
Dackis et al, 2005336 Modafinil 400 mg/day Cocaine
Dackis et al, 2012337 Modafinil 200 mg or Cocaine

400 mg/day
Heinzerling, 2010338 Modafinil 400 mg/day Cocaine, ATS
Kampman et al, 2015339 Modafinil 300 mg/day Cocaine
Kampman, 2018340 Modafinil 300 mg/day Cocaine
Kampman, 2020341 Modafinil 400 mg/day Cocaine
Karila et al, 2016342 Modafinil 200–400 mg/day Cocaine
Morgan et al, 2010343 Modafinil 200–400 mg/day Cocaine
Morgan et al, 2016344 Modafinil 100–400 mg/day Cocaine
Schmitz et al, 2012345 Modafinil 400 mg/day Cocaine
Schmitz et al, 2014346 Modafinil 200 mg BID Cocaine
Shearer et al, 2009347 Modafinil Max 200 mg/day ATS
Topiramate
214
Study Drug Dose SUD
Levin et al, 2020137 Topiramate + MAS-ER Topiramate max Cocaine

100 mg BID + MAS-
ER max 60 mg/day
Mariani et al, 2012348 Topiramate + MAS-ER Topiramate max Cocaine

150 mg BID + MAS-
ER max 60 mg/day
MAS-ER
Levin et al, 2015349 MAS-ER 60 or 80 mg/day Cocaine
Dextroamphetamine/Lisdexamfetamine
Charnaud and Griffiths, Dextroamphetamine (d-AMP) Individualized ATS

1998350
Galloway et al, 2011351 Dextroamphetamine (d-AMP-SR) 30 mg BID ATS
Grabowski et al, 2001352 Dextroamphetamine (d-AMP-SR) Max 60 mg/day Cocaine
Grabowski et al, 2004353 Dextroamphetamine (d-AMP-SR) Max 60 mg/day Cocaine
Longo et al, 2010354 Dextroamphetamine (d-AMP-SR) Max 110 mg/day ATS
Merrill et al, 2005355 Dextroamphetamine (d-AMP) Max 100 mg/day ATS
Mooney et al, 2015356 Lisdexamfetamine (LDX) 70 mg/day Cocaine
Nuijten et al, 2016357 Dexamphetamine (d-AMP-SR) 60 mg/day Cocaine
Schmitz et al, 2012345 Dextroamphetamine (d-AMP-SR) d-AMP-SR 15 mg Cocaine

+ modafinil BID + modafinil
200 mg/day
Shearer et al, 2001358 Dexamphetamine (d-AMP) Max 60 mg/day ATS
Shearer et al, 2003359 Dexamphetamine (d-AMP-SR) Max 60 mg/day Cocaine
White, 2000360 Dexamphetamine (d-AMP) Max 90 mg/day ATS
White et al, 2006361 Dexamphetamine (d-AMP) 30–60 mg/day ATS
Selegiline transdermal system patch
Elkashef et al, 2006362 Selegiline transdermal system Continuous release Cocaine

patch 6 mg/24h
215
Study Drug Dose SUD
Methylphenidate
Dürsteler-MacFarland et Methylphenidate 30 mg BID Cocaine

al, 2013363
Grabowski et al, 1994364 Methylphenidate 20–25 mg BID Cocaine
Grabowski et al, 1997365 Methylphenidate SR Max 45 mg/day Cocaine
Konstenius et al, 2010366 Methylphenidate ER 18–72 mg/day ATS
Konstenius et al, 2014367 Methylphenidate ER Max 180 mg/day Cocaine, ATS
Levin et al, 2006368 Methylphenidate SR 20–40 mg BID Cocaine
Levin et al, 2007369 Methylphenidate SR 20–40 mg BID Cocaine
Ling et al, 2014370 Methylphenidate SR 54 mg/day ATS
Miles et al, 2013371 Methylphenidate ER 54 mg/day ATS
Minařík et al, 2016372 Methylphenidate short acting Mean 37.6 mg/day ATS
Rezaei et al, 2015373 Methylphenidate SR 54 mg/day ATS
Schubiner et al, 2002374 Methylphenidate 30 mg TID Cocaine
Solhi et al, 2014375 Methylphenidate Max 10 mg/day ATS
Tiihonen et al, 2007376 Methylphenidate SR 54 mg/day ATS
Mazindol
Stine et al, 1995377 Mazindol 2 mg/day Cocaine
Margolin et al, 1995378 Mazindol 1 mg/day Cocaine
Margolin et al, 1997379 Mazindol 1 or 8 mg/day Cocaine
Perry et al, 2005380 Mazindol 2 mg TID Cocaine
Oral methamphetamine
Mooney et al, 2009381 Oral methamphetamine Immediate release Cocaine

5 mg six times daily
SR 30 mg/day
216
ATS, amphetamine-type stimulant; BID, two times per day; d-AMP, dextroamphetamine;
d-AMP-SR, sustained-release dextroamphetamine; ER, extended release; LDX,
lisdexamfetamine; MAS-ER, extended-release mixed amphetamine salts; SR, sustained
release; TID, three times per day
Table 2. Medication Dosing: Non-Psychostimulant
Study Drug Dose SUD
Bupropion
Anderson et al., 2015382 Bupropion SR 150 mg bid Methamphetamine
Das et al., 2010383 Bupropion XL 300 mg Methamphetamine
Elkashef et al., 2008384 Bupropion SR 150 mg bid Methamphetamine
Heinzerling et al., 2014385 Bupropion SR 150 mg bid Methamphetamine
Margolin et al., 1995386 Bupropion HCL 100 mg bid or tid Cocaine/ Opioid
McCann and Li 2012387 Bupropion SR 150 mg bid Methamphetamine
Poling et al., 2006107 Bupropion hydrochloride SR 300 mg/d Cocaine/ Opioid
Shoptaw et al., 2008108 Bupropion hydrochloride 150 mg bid Cocaine
Shoptaw et al., 2008388 Bupropion SR 150 mg bid Methamphetamine
Winhusen et al., 2014389 Bupropion hydrochloride XL+ 300 mg/d Cocaine/

Nicotine inhaler 6-16 cartridges/d (ad Methamphetamine
libitum)
Bupropion and Naltrexone
Mooney et al., 2016120 Bupropion (ER) and Naltrexone 450 mg/d and 380 Methamphetamine
(ER, injectable) mg (Once/month)
Trivedi et al., 2021121 Bupropion (ER) and Naltrexone 450 mg/d and 380 Methamphetamine
(ER, injectable) mg (every 3 weeks)
Mirtazapine
Coffin et al., 2020126 Mirtazapine 30 mg/d Methamphetamine
Colfax et al., 2011127 Mirtazapine 30 mg/d Methamphetamine
Cruickshank et al., 2008390 Mirtazapine 30 mg/d Methamphetamine
217
Kongsakon et al., 2005391 Mirtazapine 15-60 mg/d Amphetamine
McGregor et al., 2008289 Mirtazapine 60 mg/d Methamphetamine
Topiramate
Baldacara et al., 2016392 Topiramate 200 mg/d Cocaine
Elkashef et al., 2012123 Topiramate 200 mg/d Methamphetamine
Johnson et al., 2013393 Topiramate 100-150 mg bid Cocaine
Kampman et al., 2004394 Topiramate 200 mg/d Cocaine
Kampman et al., 2013395 Topiramate 150 mg bid Cocaine/ Alcohol
Nuijten et al., 2014396 Topiramate 200 mg/d Cocaine
Rezaei et al, 2016397 Topiramate 200 mg/d Methamphetamine
Umbricht et al., 2014398 Topiramate 150 mg bid Cocaine/ Opioid
Bid, twice a day; ER, extended-release; SR, sustained release; tid, three times a day; XL
extended-release
218
Appendix L. Acute Issues and Complications of

Acute issues and complications of stimulant intoxication and withdrawal include but are
not limited to:
• electrolyte and fluid imbalances (eg, dehydration, acidosis, hyperkalemia,
hyponatremia);
• hyperthermia;
• agitation;
• psychosis;
• cardiovascular dysfunction such as cardiac arrhythmias, hypertensive emergency,
acute decompensated heart failure, and takotsubo cardiomyopathy;
• acute neurologic complications such as seizures and cerebrovascular accidents;
• serious infections such as infective endocarditis, osteomyelitis, epidural abscesses,
septic arthritis, serious skin infections, bacteremia, and sepsis;
• rhabdomyolysis;
• movement disorders;
• gastrointestinal perforation;
• trauma and trauma-related complications; and
• risk for harm to self or others.
219
Appendix M. Non-acute Issues and

Complications of Stimulant Use
Patients with stimulant intoxication should be routinely assessed for complications and
sequalae of stimulant use and factors that impact treatment planning. Assess or refer for an
assessment of these relevant conditions and issues and treat or refer for treatment in an
appropriate medical or psychiatric setting when these conditions and issues are identified.
Non-acute issues and complications of stimulant use include but are not limited to:
• general complications, including weight change (eg, body mass index [BMI]) and
deficits in hygiene;
• cardiovascular complications, such as hypertension, arrhythmia, ischemia,
pulmonary hypertension, and heart failure;
• dental complications, such as poor dentition, dental caries, and abscesses;
• dermatologic complications, such as picking, neurodermatitis, cellulitis, abscesses,
and other skin or soft tissue infections;
• hepatic complications, such as drug-induced hepatitis;
• infectious complications, including STIs (eg, HIV, HCV);
• neurologic complications, such as involuntary movement disorders, rigidity, tremor,
seizures, stroke, and cognitive impairment (eg, deficits in memory and/or
attention);
• nutritional deficits, such as malnutrition, cachexia, and sequalae involving specific
vitamin deficiencies;
• oropharyngeal complications, such as teeth grinding and jaw clenching, earache,
headache, and facial pain;
• renal complications, such as acute kidney injury and chronic kidney disease;
• rhinologic complications such as rhinitis, mucosal atrophy, rhinorrhea, anosmia,
oronasal fistula, and septum perforation; and
• sexual dysfunction (use trauma-sensitive screening practices).
220
Appendix N. Medications for Managing

Intoxication
The information in this table is intended to guide management of stimulant intoxication in
a variety of settings. The choice of medication, medication dosing (including initial and
redosing), and route of administration should be guided by the patient’s signs and
symptoms, degree of intoxication, the level of care, and the resources of the setting. This
does not represent a comprehensive list but rather provides illustrative examples of
medications discussed in the narrative.
Agent/Class Mechanism Example dosing Indications Other considerations
Sedatives
Benzodiazepines GABAergic Initial dosing: Excitatory symptoms Parenteral vs. PO

(BZDs) (first line) administration based on
Lorazepam 1–2 mg Anxiety/Agitation
signs and symptom
IV based on clinical
Neuromuscular severity and drug
signs and symptoms
excitation availability
and duration of
Seizures (eg, parenteral BZD
effects
shortages). IM
Diazepam 5–10 mg administration allows for
PO for less severe administration in
symptoms based on agitated patients without
patient parameters IV access.
Midazolam 5 mg IM Lorazepam has very slow
or 0.01-0.05 mg/kg IM onset (15–30 min)
IV for acute
Midazolam has very
agitation in adult
rapid IV onset, allowing
patients
for easy titration, and a
Redosing frequency relatively fast IM onset
and dose should be
If psychosis is primary
guided by the
symptom, antipsychotics
degree and duration
should be considered
of the clinical effects
primarily or adjunctively
of the initial dose
221
Phenobarbital GABAergic Incremental 130– BZD shortages or High oral bioavailability;

(PBO) 260 mg contraindications PO dosing can be similar
parenteral/IV/PO to parenteral dosing
Patient not
based on symptoms
responding to Onset of effects, while
and patient
escalating doses of slower than IV, is still
parameters
BZDs fairly quick compared to
Loading strategy other PO medications
Severe
(eg, 5-10 mg/kg)
sympathomimetic
Titrate based on intoxication
clinical effects
Propofol GABAergic + 10–50 µg/kg/min For critically ill Patients can be

NMDA based on symptoms patients in the ICU administered BZDs, PBO,
receptor and patient and/or propofol
Severe
antagonism parameters concomitantly
sympathomimetic
intoxication not Intubation is almost
responding to other always required for
agents propofol administration
Sympatholytics
Clonidine Alpha-2 0.1–0.2 mg PO every Anxiety Useful medication

agonism +/- 4 hours as needed adjunct to BZDs
other
Maintain hydration to
avoid orthostatic
symptoms
Dexmedetomidine Alpha-2 Start at 0.2–0.4 For critically ill Useful medication

agonism µg/kg/hr and titrate patients in the ED or adjunct to BZDs or other
every 30 min up to ICU as primary or sedation agents
maximum of secondary medication
Onset of effects generally
1.5 µg/kg/hr for sedation
30–60 min
Sedation without
impairments in
ventilation
Antipsychotics
Butyrophenones Dopamine Haloperidol or Acute agitation with Consider atypical or

(2nd gen) antagonism droperidol 5 mg IM psychosis newer generation
antipsychotics as
Agitation not
alternatives
responding to BZDs
Consider risk of QT
Toxic psychosis
prolongation
222
Atypical Dopamine Olanzapine 5 mg PO Anxiety or agitation Consider risk of QT

antagonism with psychotic prolongation
Quetiapine 50–100
+/- other features
mg PO at night For olanzapine, degree of
Stimulant-induced symptoms to balance
psychosis need for PO vs. IM
Stimulant-induced
sleep derangements
Other
Ketamine NMDA 1–5 mg/kg IM For severe agitation as Rapid IM onset of action
receptor depending on primary or secondary compared to other
antagonism degree of agitation agent agents
BZD, benzodiazepine; ED, emergency department; ICU, intensive care unit; IM, intramuscular; IV,
intravenous; NMDA, N-methyl-D-aspartate; PBO, phenobarbital; PO, per os (by mouth/oral)
223

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The ASAM/AAAP

CLINICAL PRACTICE GUIDELINE ON THE

Clinical Guideline Committee (CGC) Members (alpha order):

Engaging Stakeholders ............................................................................................................................... 38

Monitoring ..................................................................................................................................................... 114

Secondary and Tertiary Prevention ........................................................................................................ 193

other SUDs—are common in patients with StUD. Any co-occurring psychiatric

Initial Assessment Recommendations

Comprehensive Assessment Recommendations

Behavioral Treatment Recommendations

5. Contingency Management (CM) should be a primary component of the treatment plan

a. Community Reinforcement Approach (CRA) (Low certainty, Conditional

Technology-Based Interventions Recommendations

7. Clinicians can consider offering evidence-based behavioral interventions delivered via

Non-Psychostimulant Medication Recommendations

Cocaine Use Disorder: Bupropion Recommendations

Cocaine Use Disorder: Topiramate Recommendations

Amphetamine-Type Stimulant Use Disorder: Bupropion Recommendations

Amphetamine-Type Stimulant Use Disorder: Bupropion and Naltrexone Recommendations

Amphetamine-Type Stimulant Use Disorder: Topiramate Recommendations

Amphetamine-Type Stimulant Use Disorder: Mirtazapine Recommendations

a. Clinicians can give mirtazapine additional consideration for patients with

Psychostimulant Medication Recommendations

General Psychostimulant Medication Recommendations

15. Recommendations related to the prescription of psychostimulant medications to treat

Cocaine Use Disorder: Modafinil Recommendations

Cocaine Use Disorder: Topiramate and Extended-Release Mixed Amphetamine Salts

Cocaine Use Disorder: Amphetamine Formulation Recommendations

Amphetamine-Type Stimulant Use Disorder: Methylphenidate Formulations

Co-occurring Disorders: General Guidance Recommendations

23. Symptoms of psychosis or mania should be treated with indicated pharmacotherapy

Concurrent Management of StUD and ADHD Recommendations

Population-Specific Considerations Recommendations

Adolescents and Young Adults Recommendations

Adolescent and Young Adult Assessment and Treatment Planning Recommendations

Adolescent and Young Adult Treatment Recommendations

a. consider delivering behavioral interventions that have been demonstrated to be

Pregnant and Postpartum Patients Recommendations

Pregnant and Postpartum Patients Assessment Recommendations

a. providing referrals to prenatal care providers if not already established (Low

Pregnant and Postpartum Patients Treatment Recommendations

Additional Population-Specific Considerations Recommendations

Sexual Orientation and Gender Identity Recommendations

Patients Involved in the Criminal and/or Legal Systems Recommendations

Patients Experiencing Homelessness or Unstable Housing Recommendations

Stimulant Intoxication and Withdrawal Recommendations

Initial Assessment Recommendations

Comprehensive Assessment Recommendations

Toxicology Testing Recommendations

Setting Determination Recommendations

Managing Stimulant Intoxication and Withdrawal Recommendations

Behavioral and Psychiatric Symptoms of Stimulant Intoxication Recommendations

Hyperadrenergic Symptoms of Stimulant Intoxication Recommendations

potential side effects, including poor control over tachycardia or reflex

Acute Issues and Complications Recommendations

Chest Pain Recommendations

QRS Widening Recommendations

these issues are identified, in addition to treating intoxication, clinicians should

Secondary and Tertiary Prevention Recommendations