Marijuana Use and Potential Implications of

Marijuana Legalization
Tamara M. Grigsby, MD,* Laurel M. Hoffmann, MD, MPH,* Michael J. Moss, MD†‡
*Doernbecher Children’s Hospital, Oregon Health & Science University, Portland, OR
†
Utah Poison Center, University of Utah College of Pharmacy, Salt Lake City, UT
‡
Division of Emergency Medicine, University of Utah, Salt Lake City, UT

Education Gaps
Cannabis availability and access are increasing throughout the United
States. Knowledge that marijuana demonstrates health benefits
complicates provider-patient conversations, as does the fact that
qualifying conditions for medicinal marijuana vary by state. Gaps
in longitudinal research to elucidate relationships among early
marijuana use, social determinants of health, and psychiatric
comorbidities are barriers to safeguarding the health of children
and adolescents.

Abstract
Most states in the United States have legalized medical and/or
recreational cannabis in response to public demand. Trends in states
adopting such legislation demonstrate an increasing prevalence of
cannabis use coincident to decreasing perceptions of risk of harm from
AUTHOR DISCLOSURE Drs Grigsby,
Hoffmann, and Moss have disclosed no cannabis products. When providing anticipatory guidance,
financial relationships relevant to this article. pediatricians should be prepared to address childhood unintentional
This commentary does not contain a
discussion of unapproved/investigative ingestion management and prevention, adolescent problem use, and
use of a commercial product/device. cannabis as an alternative therapy for seizure disorders and other
conditions.
ABBREVIATIONS
AAP American Academy of
Pediatrics
CBD cannabidiol
CPS Child Protective Services
Objectives After completing this article, readers should be able to:
CUD cannabis use disorder
1. Explain clinical presentations of acute exposures/ingestions of
DSM-V Diagnostic and Statistical
Manual of Mental Disorders, marijuana in children.
Fifth Edition
2. Define cannabis use disorder and symptoms of cannabis withdrawal.
ECS endocannabinoid system
RPC regional poison center 3. List potential outcomes associated with early age of initiation and
SCRA synthetic cannabinoid chronic use of marijuana in adolescents.
receptor agonist
SUD substance use disorder 4. Identify key policy issues and areas for advocacy in safety and prevention.
THC tetrahydrocannabinol
THC-COOH 11-nor-9-carboxy-D9-
tetrahydrocannabinol

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 The substances tetrahydrocannabinol (THC) and cannabi- rising in adolescents and is associated with numer-
diol (CBD) are derived from the plant Cannabis sativa. In this ous high-risk behaviors compared with marijuana use.
review, we use the terms cannabis and marijuana inter- (9)(10)(11)(12)(13)
changeably. The legal history of cannabis is complex. Can-
nabis was initially legal and listed in the US Pharmacopoeia Children
in 1851. (1) Federal regulations criminalized cannabis, Most cannabis exposure is unintentional in children youn-
through the Marihuana Tax Act of 1937 and the Controlled ger than 12 years, with the highest number of ingestions
Substances Act of 1970. (2) The criminalization of cannabis between ages 12 and 36 months. (14)(15) The rate of can-
arose alongside tensions between ethnic groups, as immi- nabis-related calls to regional poison centers (RPCs) has
gration to the United States from Mexico increased in the risen since cannabis legalization. (14)(15)(16)(17) The re-
early 1900s. (3) Figure 1 depicts the recent trends in many ports of RPC calls tend to underestimate poisonings because
states legalizing cannabis. In 2012, Colorado was the first only severe intoxications trigger caregiver calls to poison
state to legalize the use of recreational cannabis for people 21 centers.
years and older, and most states have legalized cannabis in
some form, medically or recreationally. Traditionally, can- Maternal
nabis has been consumed through inhalation, yet a diversity The American College of Obstetricians and Gynecologists
of cannabis products are now available and have become firmly recommends against any cannabis use in the peri-
more potent over time. (4)(5) Pediatricians often encounter natal period. (18) Despite these recommendations, the use
patients and parents who use cannabis products. In this of cannabis during pregnancy and lactation continues to
review, we address the health implications of recreational rise, with approximately 4% of women reporting cannabis
and medical marijuana legalization in the United States. We use during the perinatal period. (19)(20)(21) Parents who
describe patterns of its use and the clinical and toxicological use cannabis are more likely to use tobacco as well, during
effects that pediatric providers should recognize. We pre- and outside the perinatal period. (21)(22)(23)(24)
sent advocacy opportunities to keep patients and their
families safe and informed. Given the US trends in recre-
PHARMACOLOGY
ational and medical marijuana legalization, marijuana use
will impact all age groups. This review addresses clinical The term cannabinoid refers to a substance that interacts
implications along with opportunities for community en- with cannabinoid receptors. Phytocannabinoids are chem-
gagement to enhance safety and prevention. icals specifically derived from the cannabis plant. The
principal phytocannabinoids are THC, CBD, and cannabi-
nol. There are also many synthetic cannabinoid receptor
agonists (SCRAs). Endocannabinoids are endogenous mod-
EPIDEMIOLOGY
ulators of cannabinoid receptors. CB1 and CB2 are the 2
Adolescents main cannabinoid receptors. CB1 receptors are predomi-
On a population level, as adolescents age, the incidence of nantly located throughout the central nervous system, and
cannabis use increases. The rates of initiation of use, CB2 receptors are predominantly found in immune cells,
frequency of use, and progression to cannabis use disorder the spleen, and other peripheral sites. Agonism of CB1
(CUD) increase throughout adolescence. The Youth Risk receptors by THC produces the typical psychoactive effects
Behavior Surveillance System, the Monitoring the Future of marijuana. Inverse agonism of CB2 receptors by CBD
survey, the Behavioral Risk Factor Surveillance System, and causes anti-inflammatory effects. (25)(26) Inverse agonists
the National Survey on Drug Use and Health estimate reduce target receptor activity compared with antagonists,
cannabis use by adolescent self-report and demonstrate which simply block the effects of agonists.
similar trends of increasing rates in initiation, frequency, The pharmacokinetics of cannabis are well understood.
and progression of marijuana use. In the 2017 National (25)(27) When inhaled, THC is detectable in plasma within
Survey on Drug Use and Health, 6.5% of 12- to 17-year-olds seconds. Effects after smoking a single marijuana cigarette
reported current cannabis use. The prevalence is much last approximately 1 to 2 hours. Absorption of orally admin-
higher in older adolescents; 22.1% of 18- to 25-year-olds istered THC differs significantly, with peak plasma THC
report cannabis use in the same survey. (6) In high concentrations reached within 1 to 2 hours and effects
school, 35% to 49% of participants report past and/or lasting up to 6 hours. (28) THC crosses the placenta dur-
current cannabis use. (7)(8) Synthetic cannabinoid use is ing pregnancy and enters human milk during lactation.

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Figure 1. Marijuana legalization in the United States, December 2018. (Reprinted with permission from the National Conference of State Legislatures.)

(29)(30)(31)(32)(33) The pharmacodynamics and pharmaco- contains 5% THC, similar to illegal marijuana from decades
kinetics of THC in lactating women and breastfed infants past. (34)(35)(36) The cannabis flower now typically contains
remain an active area of study because the evidence of health about 20% THC. (36)(37) Newer production methods can
effects on breastfed infants exposed to THC is inconclusive. yield extracts with THC concentrations exceeding 70%. (38)
THC is metabolized primarily in the liver to the active Given these trends, novice users are at risk for consuming
metabolite 11-hydroxy-D9-tetrahydrocannabinol and then to more cannabis than necessary to achieve their desired
inactive 11-nor-9-carboxy-D9-tetrahydrocannabinol (THC- effects.
COOH). Urine drug screens detect THC-COOH for 3 to 5 Edible cannabis products (edibles) may cause toxicity in
days after a single use or for up to several weeks in long-term both recreational adolescent users and young children who
users. (25) A urine drug screen positive for THC-COOH may are unintentionally exposed to cannabis products. Recrea-
be due to acute intoxication or a marker of past use. CBD is tional users may consume excessive quantities of edibles
not metabolized to THC-COOH, and neither does it cross- because clinical effects are delayed 2 to 4 hours and the
react with THC-COOH. Thus, users of products (inhaled or listed THC content in the edibles may be underestimated.
ingested) containing only CBD would not be expected to have (39) Edibles are any of the various food items containing
THC-positive urine drug screens. Similarly, SCRAs are chem- THC and/or CBD. (40) Cannabis-infused products include
ically distinct from THC and are not detected on routine urine baked goods, gummies, candies, and chocolates and are a
drug screens. These factors are important to remember when common source of exposure in young children. (14)(41)(42)
considering differential diagnoses in patients with altered In France, where other forms of cannabis are more com-
mental status because a negative urine drug test result does mon, hashish (a product made by separating and compress-
not rule out all forms of cannabis use, and there could be ing marijuana resin) was responsible for most childhood
medical-legal implications. exposures. (15)
Symptoms of marijuana intoxication are euphoria, gid-
diness, sedation, pain relief, increased appetite, anxiety, and
CLINICAL ASPECTS
paranoia. (43)(44)(45) Signs include mild tachycardia, con-
Acute Intoxications and Effects junctival injection, and dry mouth. (46) For accidental
Acute overdose with cannabis generally falls into 3 cate- pediatric ingestions, commonly reported symptoms include
gories: novice recreational users experiencing unwanted sedation, lethargy, ataxia, tachycardia, and vomiting. Central
effects, inadvertent excessive recreational use, and uninten- nervous system and respiratory depression requiring intu-
tional ingestions by children. bation are infrequently reported. (14)(15)(17)(41)(42)(47) In
THC concentrations in modern cannabis products are these instances, it is not always clear whether intubation
now much higher than in the past. A standard marijuana was performed for true respiratory depression or whether it
cigarette from the National Institute on Drug Abuse used was prompted by other circumstances, such as a need for
in Drug Enforcement Administration–approved research transport, a perceived lack of airway protection, or unclear

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 diagnosis. Seizures and hypotension have been reported but cannabis use early in adolescence, and temporary relief of
seem to be rare. No specific end-organ damage is expected symptoms with hot showers. The cannabis hyperemesis
from marijuana intoxication. Death related to marijuana use syndrome incidence has risen with increases in cannabis
is very rarely reported, and causality is not clear. (48)(49)(50) accessibility. (53) Immunocompromised patients should
CBD is not expected to produce significant symptoms in avoid cannabis due to contaminants. Limited literature
overdose because it lacks the psychoactive effects of THC, suggests an increased risk of Aspergillus infection due to
although CBD is more sedating than placebo in clinical the presence of fungal spores in marijuana leaves and
trials. (51) Some products marketed as CBD oil have even smoke. (54)(55)(56)
been discovered to actually contain SCRAs and no CBD. (13)
The diagnosis of marijuana intoxication is largely clin- Driving
ical, but urine drug screens for THC-COOH have utility, The effect of medical and recreational marijuana legaliza-
especially in cases of children who may have inadvertently tion on motor vehicle collisions and fatalities is unclear.
been exposed to cannabis. In the appropriate clinical sce- Investigators found a decline in fatalities after legalization,
nario, a positive urine drug screen for cannabinoids may presumably from a decrease in alcohol use in the driving
obviate the need for further invasive or expensive evaluation population, but others found an increased incidence of
of a patient presenting with altered mental status. Drug collisions and fatalities. (57)(58)(59) In controlled studies
testing is not required in adolescents using cannabis unless of cannabis and driving, participants demonstrated impair-
diagnosis is uncertain or results will inform psychiatric ment in visual tracking, synergistic impairment when com-
evaluation. bined with alcohol, and impairment lasting up to 6 hours
Management of adolescents with mild to moderate symp- after smoking cannabis. (60)(61)(62)(63)(64) States have
toms of excessive cannabis use is largely supportive, with not established a standard threshold for biological sample or
the option of benzodiazepines to treat anxiety. Symptoms field sobriety test results to determine impairment. (65)
typically abate within hours. Hospital admission is rarely Many variables influence both serum THC concentrations
necessary. In one series, two-thirds of patients presenting to and impairment, such as frequency of use, time of last use,
hospitals or reported to RPCs were observed and discharged and route of exposure. Urine THC-COOH is an inappro-
home. The remainder of patients were admitted to hospital priate marker of acute toxicity because it is detected for days
wards or ICUs. (14) to weeks after use. (66)(67)
Management of young children with marijuana intoxica-
tion, although primarily supportive, also warrants Child Pro- Pregnancy, Infants, and Young Children
tective Services (CPS) notification. If exposure and diagnosis There is substantial evidence of low birthweight in infants
are not in question (eg, found eating a marijuana brownie), born to mothers smoking cannabis. (68) Evidence is insuf-
the stable child may be observed for 4 to 6 hours and ficient to determine statistically significant positive or neg-
discharged to a safe environment. Gastrointestinal decon- ative associations between maternal cannabis smoking and
tamination with activated charcoal may be considered early pregnancy complications or prematurity. (68) Maternal
after ingestion. In the rare instances of more serious effects, marijuana use did not increase neonatal complications such
treatment and intervention for central nervous system and as jaundice, respiratory distress syndrome, resuscitation,
respiratory depression, seizures, or hypotension may be intubation, hypoglycemia, and sepsis, but there is a small
required. but persistent positive association between prenatal canna-
Although commonly known as “spice” or “K2,” there are bis use and NICU admission. (68)(69)(70)(71) Withdrawal
dozens of different SCRAs that produce a variety of effects. syndrome symptoms have not been observed in cases of in
Intoxication with SCRAs is generally more severe than utero exposure to cannabis only.
marijuana, with common effects including agitation, delir- The effects of cannabinoids on the developing endocan-
ium, and seizures. (52) A history of “synthetic marijuana” nabinoid system (ECS) are not clear. In the fetal brain, CB1
use, or symptoms inconsistent with traditional THC intox- receptors are found in areas important for emotional reg-
ication, should raise suspicion for intoxication with an ulation, cognition, and memory. In the early stages of
SCRA or other novel psychoactive substance. embryonic development, ECS activity influences neuronal
Cannabis poses other short-term health risks in addition connections, paving the way for endocannabinoid modula-
to acute intoxication. Cannabis hyperemesis syndrome, tion of synaptic transmission in the postnatal brain and
often seen in adolescents, is distinct from acute intoxication spinal cord. Repeated exposure to THC disrupts endocan-
and is characterized by intractable vomiting, initiation of nabinoid signaling in the fetus, facilitating rewiring of the

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fetal cortical circuitry and possibly altering ECS function- provided insufficient evidence to support or refute a statis-
ality. (66) Research combining results of animal studies and tical association between cannabis smoking and asthma
what is known about neurophysiology and genetic muta- development or exacerbations. (83)(84) Studies of perinatal
tions in humans with diagnoses such as schizophrenia, cannabis exposure on long-term child health outcomes are
bipolar disorder, and drug addiction supports causality confounded by variations in socioeconomic status, maternal
between dysregulated ECS signaling and neuropsychiatric educational achievement, mental illness, and comorbidity
illnesses. (72) with other substance use. (68) Investigators were not able to
Only approximately half of women disclosing marijuana control for dose and duration of cannabis exposure, recall
use received counseling on associated perinatal health risks. bias from self-report, and route of exposure. (68)
(73) Women seeking information about cannabis use during
and after pregnancy are looking beyond that provided by The Social Context of Cannabis
traditional health-care providers. Online media sources Adults responsible for supervising children and adolescents
suggest use of marijuana to relieve nausea and vomiting should not be under the influence of alcohol, marijuana, or
during pregnancy but do not systematically present the risks other drugs. (85) State mandatory reporting laws require
and benefits; 69% of dispensaries surveyed in Colorado CPS notification when women test positive for illicit sub-
recommended cannabis for morning sickness. (74)(75) stance use during pregnancy and/or at the time of birth.
Rising maternal cannabis use occurs alongside increasing Parental substance abuse contributes to adverse childhood
prevalence of preexisting conditions, including hypertension, experiences, which disproportionately affect families living
chronic lung disease, diabetes, and substance use disorder in poverty and historically marginalized populations.
(SUD) in reproductive-aged women. (76) In prenatal visits, (86)(87)(88) Clinicians can inadvertently compound the
providers (and health systems) have competing interests as impact of adverse childhood experiences when they fail to
they address conditions that have well-known, often quantifi- consider the role of implicit bias in their treatment of
able risks to the mother and fetus. Under the umbrella of patients from racially, socioeconomically, and gender-
SUD (which includes CUD), substances such as opioids diverse populations. In a study of prenatal alcohol and drug
require complex prenatal and postnatal management and use, white and black women tested positive for these sub-
may take precedence over cannabis counseling. (77) stances at similar rates when universally screened. In the
same study population, black women were nearly 4 times as
Breastfeeding likely to be reported to CPS than white women. (89) Other
Research into the effects of cannabis exposure on breastfed investigations have demonstrated similar imbalance in the
infants and young children is insufficient to determine medical-legal system regarding CPS involvement; and per-
associations with developmental delays. The American sistent racial disproportion in health outcomes and access
Academy of Pediatrics (AAP) and the Academy of Breast- to care are well-documented throughout adult and pediatric
feeding Medicine recommend weighing risks and benefits medicine. (75)(90)(91)(92)(93) Practitioners can incorpo-
when counseling about breastfeeding. Pattern of use and rate equitable standards of care to address child injury
effects on parenting practice should be discussed, and prevention (eg, universal mandatory reporting of illicit sub-
providers should inform women of the potentially harmful stance use), screen for perinatal mood disorders (including
effects of cannabis on early childhood brain development. SUDs), and promote neighborhood safety. Informed care
The Academy of Breastfeeding Medicine guidelines note models mitigate health disparities and empower parents,
that “although the data are not strong enough to recom- better served by an evidence-based, integrated approach to
mend not breastfeeding with any marijuana use, we urge early learning, comprehensive health services, and family
caution.” (78) support. The principles of nurturing and stable relation-
ships between children and caregivers can be stepping
Later Childhood Outcomes stones for discussing substance use in an unbiased, non-
The results of 3 large cohort studies—the Ottawa Prenatal punitive way. (94)(95)
Prospective Study, the Maternal Health Practices and Child
Development study, and the Generation R Study—serve as a Risk Behavior in Adolescence
major basis for conclusions regarding later health effects in Social learning and risk behavior patterns impact cannabis
children exposed to marijuana prenatally. (79)(80)(81) An use and its consequences in adolescents. Parents using
AAP Clinical Report concludes that marijuana use during cannabis are not routinely discussing cannabis use with
pregnancy may not be harmless. (82) Research overall has their children. (96) After alcohol, cannabinoids were the

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 second most common substance detected in a study of drug- and suicide completion. (111)(112) Except for social anxiety
facilitated sexual assaults. (97) Driving after marijuana use disorder, cannabis use does not seem to have a statistically
may be perceived as safer than driving after alcohol use, significant association with anxiety disorders. (113)(114)
when in fact both cause substantial driver impairment. Although data do not suggest an increased likelihood of
(98)(99) The 2018 AAP policy statement, The Teen Driver, bipolar disorder or posttraumatic stress disorder, cannabis
explores new risks facing adolescent drivers and provides use was strongly associated with alcohol use disorder, other
guidance to parents and teens regarding impaired driving SUDs, and nicotine dependence. (115)
caused by the use of alcohol, prescription and nonprescrip-
tions drugs, or combinations thereof. (100) Smoking is the Adolescent Problem Use
most common method of cannabis consumption. Of note, CUD is classified as a SUD in the Diagnostic and Statistical
cannabis smoke contains carcinogens similar to those in Manual of Mental Disorders, Fifth Edition (DSM-V), and
tobacco. Discussion of the hazards of smoking, vaping, and approximately 20% of lifetime users met the DSM-V criteria
inhalation of substances should be countered with efforts to for CUD. (116)(117) Of the 23% of individuals with severe
assist teens in cessation. Evidence is insufficient to deter- CUD, 48% were unemployed and undereducated. (118)
mine whether cannabis use is associated with heart attacks, Individuals with CUD are vulnerable to other substance
stroke, and diabetes. (2) abuse and mental health illness and are more likely to
experience significant disability. (116) Clinical diagnosis
Adolescent Learning of cannabis withdrawal requires 3 of 7 symptoms developing
Volkow et al (101) summarize the myriad of adverse effects within 1 week of cessation or reduction of prolonged can-
of cannabis by duration of use in Table 1. There is moderate nabis use: 1) irritability, anger, or aggression; 2) nervousness
evidence of a statistically significant positive association or anxiety; 3) sleep difficulty; 4) decreased appetite or weight
between acute cannabis use (within 24 hours of evaluation) loss; 5) restlessness; 6) depressed mood; and 7) somatic
and immediate impairment in the cognitive domains of symptoms causing significant discomfort. (117) The 15-item
learning, memory, and attention. (2) Effects were not sus- Marijuana Withdrawal Checklist lists additional withdrawal
tained after a period of cessation, with periods ranging from symptoms less frequently reported. (119) No standardized
12 hours to 1 month. (102)(103)(104)(105) Beale et al (106) withdrawal scales are yet available. (120)(121)
reviewed research using functional magnetic resonance In a large national study of adults, the lifetime cumula-
imaging during cognitive testing of adult and adolescent tive probability of transition from use to dependence was
cannabis users. Verbal learning, memory, and attention were 67.5% in nicotine users, 22.7% in alcohol users, 20.9% in
most consistently impaired by short- and long-term exposure cocaine users, and 8.9% in cannabis users. (122) Individuals
to cannabis. (106) Psychomotor function was most affected from certain ethnic minority groups and those with psychi-
during acute intoxication. (102) Cannabis initiation at 14 years atric and substance dependence comorbidities showed an
or older was associated with larger differences in brain increased risk of transitioning from use to dependence.
function, suggesting that stages of critical neurodevelopment There is substantial evidence that being male and smoking
impart greater vulnerability. (103) Daily users of cannabis who cigarettes, and earlier age of initiation, are risk factors for
started using before age 17 years were less likely to complete problem cannabis use. (2)
high school and more likely to develop cannabis dependence, Characteristics of frequent users who develop depen-
use illicit drugs, and attempt suicide. (107) dence include cannabis use as a coping strategy, inability to
control desire or cut down use, and number of negative life
Adolescent Mental Health events. (123) In a review of longitudinal studies, Courtney
In 2014, a national survey from the Substance Abuse and et al (124) opined that the adolescent peer environment, past
Mental Health Services Administration identified 20.2 mil- substance use, and pre/comorbid psychopathology (ie, con-
lion adults with SUD, and among these, 7.9 million had duct disorder, mood disorders) significantly influence the
both a mental health disorder and SUD. (108) Research risk of transition to CUD. In research combining functional
suggests that predisposing risk factors (genetics, environ- brain magnetic resonance imaging, behavioral studies re-
ment) contribute to the development of comorbidity. There lating peer factors with adolescent cannabis use, and neu-
is substantial evidence for an association between cannabis roscience models of regulatory and motivational systems,
use and psychotic outcomes, with the most frequent and Caouette and Feldstein Ewing (125) opined that the reward-
earliest cannabis users at highest risk. (109)(110) Heavy ing value of cannabis use and the propensity to avoid neg-
cannabis users have a higher incidence of suicide attempts ative peer evaluation were essential to decision-making in

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TABLE 1. Adverse Effects of Short-Term Use and Long-Term or Heavy Use
of Marijuana (101)
Effects of short-term use
Impaired short-term memory, making it difficult to learn and to retain information
Impaired motor coordination, interfering with driving skills and increasing the risk of injuries
Altered judgment, increasing the risk of sexual behaviors that facilitate the transmission of sexually transmitted diseases
In high doses, paranoia and psychosis
Effects of long-term or heavy use
Addiction (in w9% of users overall, 17% of those who begin use in adolescence, and 25% to 50% of those who are daily users)a
Altered brain developmenta
Poor educational outcome, with increased likelihood of dropping out of schoola
Cognitive impairment, with lower IQ among those who were frequent users during adolescencea
Diminished life satisfaction and achievement (determined on the basis of subjective and objective measures compared with such ratings in the
general population)a
Symptoms of chronic bronchitis
Increased risk of chronic psychosis disorders (including schizophrenia) in persons with a predisposition to such disorders
a
The effect is strongly associated with initial marijuana use early in adolescence.

adolescents (Fig 2). The authors suggest 4 mechanistic of substance abuse prevention and mental health
models to explain teen behavior: 1) high social approach, promotion.
lower reward sensitivity—using cannabis to fit in, not
primarily to get “high”; 2) high social approach, higher Potential Medical Uses in Minors
reward sensitivity—using cannabis mainly to explore the The AAP currently opposes the decriminalization of mar-
“high,” less influenced by peers; 3) high social avoidance, ijuana, as well as the dispensing of medical marijuana to
high reward sensitivity—using cannabis to ease anxiety and children and adolescents when dispensed outside Food and
“escape” negative perceptions by peers; and 4) high social Drug Administration (FDA) regulation committee policies.
avoidance, low reward sensitivity—using cannabis to reduce (82)(127) The AAP has acknowledged that cannabis and
anxiety and depression and to cope with psychological cannabinoid preparations may benefit children and youth
consequences of negative experiences (eg, bullying, victim- with life-threatening and severely debilitating conditions
ization). These early models begin to deconstruct the com- refractory to current therapies. (82)(127) Using cannabis
plicated psychosocial and neurodevelopmental factors that products as alternative and complimentary therapies for
influence adolescent cannabis use. (125) Similar emerging challenging conditions raises ethical concerns for families
research underlines the pediatrician’s obligation to consider and pediatricians. (128)
the social environment in which adolescents undertake
substance exploration.
Effective screening is contingent on the availability of
appropriate and accessible substance abuse treatment
programs. In the state of Washington, marijuana misuse
and abuse are state priorities. Using the Substance Abuse
and Mental Health Services Administration Strategic
Prevention Framework, state and community prevention
stakeholders assessed, planned, and implemented a 5-
year strategic plan using a data-driven process (Fig 3). Figure 2. A mechanistic model of peer influence on adolescent cannabis
use. (Reprinted with permission from Caouette JD, Feldstein Ewing SW.
(126) Ongoing program evaluation and cultural com-
Four mechanistic models of peer influence on adolescent cannabis use.
petency help make this a sustainable statewide system Curr Addict Rep. 2017;4(2):90–99.)

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 Figure 3. Summary of key elements, Washington State 5-year strategic plan for substance abuse prevention and mental health promotion, November
2017. (Reprinted with permission from The Athena Forum, Washington State Prevention Enhancement Policy Consortium.)

Double-blinded randomized controlled trials have dem- effectiveness. Short-term adverse effects were balance
onstrated the safety and efficacy of cannabidiol (CBD), an problems, confusion, dizziness, diarrhea, euphoria,
oral solution, now an FDA-approved option for treatment- drowsiness, dry mouth, hallucination, nausea, somno-
resistant epilepsy, including convulsive seizures in Dravet lence, and vomiting. No studies evaluated long-term
syndrome and drop seizures in Lennox-Gastaut syndrome. adverse effects of cannabis prescribed for indicated
(51) CBD therapy does not work well for all patients with conditions.
treatment-refractory seizures, and there is insufficient evi- Medical marijuana is legal in most states and the
dence to support CBD for the treatment of childhood anxiety District of Columbia. States have autonomy to implement
and posttraumatic stress disorder. (2)(129) marijuana laws and define qualifying conditions. Some
Whiting et al (130) performed a systematic review and states have limited legalization to nonpsychoactive CBD,
meta-analysis of the quality of evidence available to de- whereas others authorize all portions of the cannabis
termine the effectiveness of cannabinoids in various plant for medicinal use. Medical marijuana in legalized
conditions. They noted moderate-quality evidence that states is available to minors with physician authorization
cannabinoids are effective for chronic neuropathic or and consent of a legal guardian, despite known disrupting
cancer pain and for spasticity due to multiple sclerosis. effects on neuropsychological development and limited
(130) In many conditions, findings were inconclusive due evidence of efficacy in pediatric populations. Legal pro-
to the lack of high-quality evidence. Similarly, evidence for tection for physicians prescribing medical marijuana
nausea and vomiting in patients receiving chemotherapy, varies by state. (131) Pediatricians should be ready to
weight gain in patients with human immunodeficiency discuss undesirable health effects and discourage expo-
virus, sleep disorder, and Tourette syndrome was lower- sures while acknowledging the emerging science of
quality and, thus, inconclusive regarding cannabinoid health benefits.

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TABLE 2. Lessons in Advocacy
CURRENT STATE RECOMMENDED ACTIONS

1. Medical and recreational cannabis users are diverse populations Understand population demographics and customize
with varying motives, patterns of use, and risks of developing public health messages.
cannabis use disorder, polysubstance abuse, and mental illness.
Public health messages need to appeal to many audiences.
2. Cannabis nonusers seek more information about marijuana laws Pass local ordinances to promote abstinence in
and adverse effects after state legalization than do current users. nonusers and warn users at retail sites of health
(132) Despite no state prohibitions to block public messages at hazards.
retail sites, Dilley et al (133) found no cities or counties in
Washington State that required restrictions on marijuana
advertising or directives for messaging aimed to counter pro-
marijuana marketing.
3. Pregnant women use marijuana to relieve nausea, vomiting, and Implement statewide provider educational training and
anxiety. In Vermont, stakeholders recommended expansion of expanded screening for substance use.
screening for marijuana use and education of health-care
providers, opting for a public health and medical approach to
substance use during pregnancy. (134)
4. Medical and recreational legislation needs to be logical. Lack of Target logical, coherent regulations of medical and
alignment of recreational and medical marijuana legalization recreational marijuana.
regulations in Colorado led to discrepancies in taxation, allowable Mirror marijuana policies to reflect effective policies
amounts for possession, testing requirements, and labeling/ limiting youth access and media exposure to alcohol
packaging. (135) Lessons from alcohol and tobacco control and nicotine.
suggest that preventing use among youth and minimizing harms
to adults is better accomplished by policies germane to
communities. (133)
5. Policy surveillance at the community (versus the state) level is Direct policy surveillance to highlight what measures are
required to better understand its implementation and identify keeping the public safe.
communities successfully mitigating negative impacts of legal
marijuana. (131)
6. Cannabis smoke and edibles are appearing in homes, threatening Guide local measures to reduce harm, eg, ban home
poisonings, worsening asthma control, and calling attention to delivery; limit hours of retail operation; require
caregiver behavior and relaxed attitudes assuming marijuana is dispensaries to publicize addiction hotlines; enforce
safe. buffer zones.a
7. Federal restrictions on marijuana necessitate that all product State-controlled reference laboratories could verify
testing be performed within each state. Accurate testing for THC/ concentration and potency of THC/CBD and screen
CBD concentrations, pesticide and microbial contaminants, and for product contaminants to inform and protect the
residual solvents is imperative to public health and trust. States public.
should establish laboratories and amend regulations based on
analysis of reliable data and scientific discovery. (136)

CBD¼cannabidiol, THC¼tetrahydrocannabinol.
a
Buffer zones are zonal areas that segregate regions and serve various purposes. Regarding marijuana legislation, buffer zones serve to shield and
protect residential areas, schools, places of worship, rehabilitation facilities, and commercial businesses from exposure to marijuana growers and
dispensaries.

SUGGESTED ANTICIPATORY GUIDANCE • Early and long-term marijuana use are risk
factors for SUD with adverse mental health out-
• Pediatricians can organize initiatives to distribute comes. Three of 10 casual cannabis users will
lockboxes for safe storage of cannabis in homes and develop CUD.
provide information about local RPCs at health • Children and adolescents with a family history of
supervision visits. (14) psychosis should be educated about the risks of can-
• When it is necessary to perform urine toxicology nabis use and be advised not to use cannabis.
screens, providers should obtain informed consent and • Immunocompromised patients should be educated
remind parents that federal law categorizes cannabis as about the risk of serious infection from handling, con-
an illicit substance, mandating reports to local CPS of suming, vaporizing, and inhaling dispensary-sourced
pediatric exposures to marijuana. cannabis.

Vol. 41 No. 2 FEBRUARY 2020 69

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 • Providers in academic and community settings can
standardize screening for cannabis using evidence- about the positive or negative associations between perinatal
based tools such as CRAFFT (Car, Relax, Alone, Forget, outcomes and cannabis use.
Friends, Trouble) and SBIRT (Screening, Brief Inter- • The clinical presentation of cannabis exposure varies widely, and
vention, and Referral to Treatment) per AAP Bright data are based on observational investigations and case reports.
Clinicians should consider cannabis exposure in any patient with
Futures guidelines.
altered mental status, with or without vital sign instability.
• Pediatricians can empower parents to advocate for
• Based on randomized controlled trials, cannabidiol oral solution is
prevention through statewide investments in mental
currently Food and Drug Administration (FDA)–approved for the
health resources in schools and libraries, using evi- treatment of refractory seizures and specific seizure disorders.
dence-based protocols in neighborhood programs to There are currently no other FDA-approved cannabis-derived
tackle youth marijuana use, and local ordinances for preparations for medicinal use in pediatric patients.
educating the public and restricting exposure to mar- • Experimental studies demonstrate obvious motor vehicle driver
ijuana in their communities (Table 2). impairment when under the influence of THC. Population-level
evidence does not support an association between cannabis use and
increased incidence of motor vehicle collisions; however,
SUGGESTED READINGS AND WEB RESOURCES epidemiologic studies are more confounded than laboratory
studies.
The Colorado Marijuana page of the Colorado Official State • Based on expert opinion, teens and young adults should avoid
Web Portal (https://www.colorado.gov/marijuana) provides consumption of marijuana. The adolescent brain is uniquely
information on laws and health effects of retail marijuana. It vulnerable to cannabis exposure with short- and long-term health
contains patient-friendly language in presenting up-to-date, effects. Cannabis use is strongly associated with alcohol use
relevant science. disorder and nicotine dependence, and there is substantial
evidence for a positive association between cannabis use,
The University of Washington Alcohol & Drug Abuse
suicidality, and psychosis.
Institute’s Learn About Marijuana webpage (http://learna-
• Based on the lack of evidence of the safety of cannabis use in
boutmarijuanawa.org/index.htm) is a hub for research, policy pregnant and lactating women, adolescents, and children,
and law updates, factsheets, videos, and e-learning modules pediatricians should follow the precautionary principle, ie,
for consumers, teens, parents, and providers. advising their patients to avoid exposure to a potentially harmful
The National Conference of State Legislatures’ State Med- material until safety has been established.
ical Marijuana Laws website (http://www.ncsl.org/research/
health/state-medical-marijuana-laws.aspx) displays state and
federal perspectives and resources. They update a “deep dive
To view teaching slides that accompany this article,
page” with the newest policy trends and analyses.
visit http://pedsinreview.aappublications.org/
content/41/2/61.supplemental.

Summary
• Based on many observational cohort investigations, the
incidence of cannabis use is increasing in adolescent and adult
populations, as well as in children due to unintentional ingestion.
Pediatricians can track trends in marijuana use, attitudes, and
health effects by accessing state health department impact
reports and publicly available national survey data sets.
• Numerous toxicological investigations and reliable observational
studies provide strong evidence showing that cannabidiol and
tetrahydrocannabinol act on distinctive receptors throughout the
body and use different metabolic pathways. Clinical and legal
conclusions drawn from these results should be interpreted
prudently based on knowledge of these diverse systems.
• Based on a comprehensive literature review of perinatal
outcomes, there is a statistically significant association between
prenatal cannabis use and low birthweight. High-quality
evidence is not available from which to draw strong conclusions References for this article are at http://pedsinreview.aappub-
lications.org/content/41/2/61.

70 Pediatrics in Review
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PIR Quiz
Individual CME quizzes are available via the blue CME link under the article title in the Table of Contents of any issue.
To learn how to claim MOC points, go to: http://www.aappublications.org/content/moc-credit.

1. A 20-month-old infant was found by his mother eating a brownie known to contain REQUIREMENTS: Learners
marijuana. In the first half hour after ingestion the infant seemed to be his usual and can take Pediatrics in Review
normal self. In the ensuing hour he became increasingly irritable and ataxic. Which of the quizzes and claim credit
following is the best explanation for the delay in manifestation of this infant’s irritability online only at: http://
and ataxia? pedsinreview.org.
A. Initial and early manifestations of euphoria due to marijuana ingestion is difficult to To successfully complete
recognize in infants. 2020 Pediatrics in Review
B. Plasma concentration of ingested tetrahydrocannabinol peaks within 1 to 2 hours articles for AMA PRA
after ingestion. Category 1 CreditTM, learners
C. Reduced sensitivity and paucity of CB1 receptors present in the brains of infants. must demonstrate
D. Slow release of cannabidiol (CBD) in edibles. a minimum performance
E. The infant was likely chronically exposed to inhaled and ingested marijuana. level of 60% or higher on
2. A 17-year-old boy is brought to the clinic for evaluation of recurrent episodes of nausea, this assessment. If you score
abdominal pain, and vomiting with a 22-lb (10-kg) weight loss during the past 3 months. less than 60% on the
He reports that long hot showers provide him with some relief of symptoms. He began assessment, you will be
using marijuana at age 13 years. During the past 2 years, the frequency of his marijuana use given additional
has increased to almost daily and includes smoking and consumption of edibles. He also opportunities to answer
has a history of binge alcohol use and tobacco use. Which of the following diagnoses is questions until an overall 60%
consistent with this patient’s presentation? or greater score is achieved.
A. CBD use toxicity. This journal-based CME
B. Cannabis hyperemesis syndrome. activity is available through
C. Cannabis withdrawal. Dec. 31, 2022, however, credit
D. Phencyclidine-contaminated cannabis use. will be recorded in the year in
E. Synthetic cannabinoid use. which the learner completes
3. A 16-year-old girl is brought to the clinic to establish care. She is accompanied today by her the quiz.
grandmother who recently obtained custody of her. They have lived together for the past 2
weeks. The grandmother is concerned because her initially pleasant granddaughter has
become easily angered and has a decreased appetite. It has also been a struggle to get her
granddaughter to school on time. The girl has a known history of smoking marijuana that
began in middle school. For this patient, which of the following additional findings will
substantiate a clinical diagnosis of cannabis withdrawal? 2020 Pediatrics in Review is
A. Bilateral hand tremors. approved for a total of 30
B. Hallucinations. Maintenance of Certification
C. Hypertension. (MOC) Part 2 credits by the
D. Sleep difficulties. American Board of Pediatrics
E. Tachycardia. (ABP) through the AAP MOC
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Vol. 41 No. 2 FEBRUARY 2020 71

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 4. A 13-year-old girl who has a diagnosis of juvenile myoclonic epilepsy that requires long-
term treatment is followed in the clinic. She responded well to the initial treatment with
sodium valproate and has been seizure free for 1 year. The mother is concerned about
teratogenic risks of valproate and asks the clinician about the option of treating her
daughter with marijuana. The clinician’s discussion with the mother acknowledges
the emerging science of possible health benefits of marijuana. The clinician reviews
the availability of a wide array of marijuana products and the variability of
tetrahydrocannabinol and CBD content. However, the clinician expresses concerns about
the vulnerability of adolescent brain function to marijuana and adverse effects associated
with short- and long-term use. The clinician shares with the mother that randomized
controlled clinical trials have demonstrated the safety and efficacy of CBD oil solution, and
consequently Food and Drug Administration (FDA) approval for the treatment of which of
the following clinical conditions?
A. Certain treatment-resistant seizures.
B. Menstrual cramps.
C. Morning sickness of pregnancy.
D. Posttraumatic stress disorder.
E. Spasticity due to cerebral palsy.
5. A 16-year-old boy has been smoking marijuana almost daily for the past month. When
available he also consumes edibles. He has a long history of school truancy and first
smoked marijuana at age 12 years with an older brother. He tells you that marijuana helps
him cope with stress and he often smokes it alone. You are concerned that this adolescent
is at risk for short- and long-term health consequences of his cannabis use. There is
substantial evidence that his cannabis use increases his risk for which of the following
conditions?
A. Bipolar disorder.
B. Cardiovascular disease.
C. Liver toxicity.
D. Posttraumatic stress disorder.
E. Suicidality.

72 Pediatrics in Review
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 Marijuana Use and Potential Implications of Marijuana Legalization
Tamara M. Grigsby, Laurel M. Hoffmann and Michael J. Moss
Pediatrics in Review 2020;41;61
DOI: 10.1542/pir.2018-0347

Updated Information & including high resolution figures, can be found at:
Services http://pedsinreview.aappublications.org/content/41/2/61
Supplementary Material Supplementary material can be found at:
http://pedsinreview.aappublications.org/content/suppl/2020/01/31/41
.2.61.DC2
References This article cites 121 articles, 8 of which you can access for free at:
http://pedsinreview.aappublications.org/content/41/2/61.full#ref-list-
1
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 Marijuana Use and Potential Implications of Marijuana Legalization
Tamara M. Grigsby, Laurel M. Hoffmann and Michael J. Moss
Pediatrics in Review 2020;41;61
DOI: 10.1542/pir.2018-0347

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pedsinreview.aappublications.org/content/41/2/61

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