12 | Recreational: Hallucinogens and Cannabis

1. Overview of Hallucinogens
a. Covers a wide variety of drugs from multiple classes
b. Lower risk of abuse, dependence, or personal/societal harm than stimulants or depressants
c. Physiologic effects, if any, are not consistent
d. Three main classes: cannabis, serotonergic psychedelics, and dissociative psychedelics
i. Note: Cannabis is not considered a hallucinogen, but is often grouped in this category
for convenience
2. Cannabis (Marijuana, Pot, Weed, Grass, THC, etc.)
a. Widely used (4% of the world’s population has used at least once in the past year)
b. Cognitive effects include euphoria/relaxation and, occasionally, paranoia
c. Physiologic signs and symptoms include increased appetite and conjunctival injection
d. Withdrawal effects are inconsistent but may include anxiety, insomnia, and anorexia
e. Mechanism: Bind to cannabinoid receptors, which modulate appetite, pain, memory, and mood
f. Not associated with significant morbidity or mortality
g. Possible link to psychosis in vulnerable individuals
3. Synthetic Cannabis (Spice, K2)
a. Newer, more potent form of cannabis
b. More significant side effects (including withdrawal state and a stronger link to psychosis)
c. Not illegal (easily purchased as “incense” or “potpourri”)
4. Serotonergic Psychedelics
a. Mechanism: Alters serotonin in the frontal cortex
i. One function of serotonin is to synthesize various senses (sight, sound, touch, etc.)
b. Cognitive effects include primarily sensory abnormalities
i. Users may also report feelings of “oneness” or “connectedness”
ii. May occasionally exacerbate anxiety and paranoia (“bad trip”)
c. All serotonergic psychedelics are similar from a clinical standpoint
d. Examples include:
1. Lysergic Acid Diethylamine (LSD)
2. Mescaline (peyote)
3. Psilocybin (“magic mushrooms,” “shrooms”)
e. Physiologic effects unclear or non-existent
f. Negligible withdrawal effects
g. Least harmful recreational drugs, rarely cause dependence
i. Potential negative effect: hallucinogen persisting perception disorder (HPPD)
1. Involves persistent sensory abnormalities (halos, visual snow, etc.) even after
drug has been discontinued
5. Dissociative Psychedelics
a. Characterized by a state of dissociation (person reports
b. Mechanism: Glutamate antagonist (NMDA subtype)
c. Phencyclidine (PCP)
i. Known for causing belligerence, agitation, impulsiveness, psychosis, and delirium
ii. Reports of making patients impervious to pain (“took 5 nurses to restrain him”)
iii. Causes horizontal, vertical, and/or rotary nystagmus
iv. Withdrawal state poorly characterized
d. Ketamine (Ketalar, “Vitamin K”
i. Used recreationally as a club drug
ii. Used clinically for emergency anesthesia, most often in pediatrics
iii. Patients report feelings of depersonalization, detachment, euphoria, loss of time
perception, and spiritual revelations
iv. Withdrawal state uncertain, possibly non-existent after short-term use

Cannabis can cause paranoia, euphoria, increased appetite, and red eyes.
þ PEER: Paranoia, Euphoria, Eating, and Red Eyes
 PCP can cause extreme agitation and belligerence.
þ “Takes 5 nurses to restrain him” = PCP!

þ PCP intoxication causes horizontal and vertical nystagmus.

“It’s all in the eyes”

þ Mydriasis = Stimulants
Miosis = Depressants
Nystagmus = PCP
Red Eyes = Cannabis
   
Practice Questions

1. Which of the following classes of drugs is considered to be least harmful in terms of both personal and
societal harm?
a. Alcohol
b. Cocaine
c. Amphetamines
d. Marijuana
e. Opiates
f. Benzodiazepines
g. Serotonergic Psychedelics
h. Caffeine
i. Nicotine

2. A 26 y/o M is brought into the ED by police officers responding to a call. According to several 911 calls,
the patient was seen wandering through the streets yelling angrily and smashing mailboxes. At present
time, he appears calm but disoriented. He does not respond to questions. On exam, significant
nystagmus is noted. The patient becomes increasingly agitated throughout the exam and suddenly
erupts and begins attacking nearby medical personnel. It takes 6 nurses to finally restrain him. The
substance that the patient was most likely taking has what mechanism of action?
a. GABA agonist
b. GABA antagonist
c. Glutamate agonist
d. Glutamate antagonist
e. Serotonin agonist
f. Serotonin antagonist

3. A 16 y/o M has recently begun smoking marijuana with several of his older friends. Which of the
following signs or behaviors is most likely to be observed in this patient while intoxicated?
a. Decreased eating behavior
b. Bilateral conjunctival injection
c. Agitation and belligerence
d. Reports of depersonalization and derealization
e. Increase in pain sensation

4. Which of the following side effects is incorrectly paired with its causative agent?
a. Mydriasis – Stimulant intoxication
b. Miosis – Depressant withdrawal
c. Red eyes – Cannabis intoxication
d. Rotary nystagmus – Phencyclidine intoxication

5. A 46 y/o M has found employment as a truck driver. While on his first drive from California to Florida,
he notices that his vision of the west Texas desert is altered. Specifically, the horizon line between the
desert ground and the blue sky is not straight but rather appears to be an undulating wave. In addition,
he notices several visual halos in the sky. He is concerned by this but, seeing that it does not impact his
driving, he decides to keep going. What substance was most likely used several years prior?
a. Marijuana
b. Mescaline
c. Methampthamine
d. Midazolam
e. MDMA
 1. The correct answer is G. Multiple studies have demonstrated that the personal and societal harm
caused by serotonergic psychedelics can be considered negligible when compared with the other drug
classes listed.

2. The correct answer is D. This clinical vignette describes a patient who is intoxicated with phencyclidine,
as evidenced by his extreme agitation. Phencyclidine is considered to be a potent glutamate antagonist
at the NMDA receptor subtype (answer D), as well as having some effect as a dopamine agonist. None
of the other answer choices correctly describes phencyclidine’s mechanism of action.

3. The correct answer is B. Use of cannabis is reliably associated with multiple signs and symptoms.
These include reported feelings of euphoria and relaxation, decreased pain sensation, increased appetite
and eating behavior, occasional feelings of paranoia, and bilateral conjunctival injection (answer B). None
of the other answer choices correctly describes the effects of cannabis use.

4. The correct answer is B. Depressant intoxication, not withdrawal, is associated with miosis (pupillary
constriction). All of the other answer choices are correctly paired with their causative agent.

5. The correct answer is B. This vignette describes a patient who is experiencing Hallucinogen Persisting
Perception Disorder (HPPD), a syndrome that is characterized by persistent sensory abnormalities
occurring after the discontinuation of long-term use of serotonergic psychedelics. Of the answer choices
listed, only mescaline (answer B) can be considered a serotonergic psychedelic. None of the other drugs
listed has been shown to cause HPPD.