Other Drugs of Abuse: Cannabis and Hallucinogens

Question 1

______ is the most widely used illicit substance in the United States. ______ ______ produces the psychoactive compound ______.

Answer 1

Marijuana; cannabis sativa; THC

Question 2

There are two cannabinoid receptor subtypes (____ and ____), which have ______ effects on cells via ______ of adenylyl cyclase and voltage-gated ____ channels or ______ of ____ channels.

Answer 2

CB1; CB2; inhibitory; inhibition; Ca2+; stimulation; K+

Question 3

Endogenous cannabinoids (______) operate by ______ ______ to reduce ______ release of neurotransmitters. This alleviates ______ stimulus on the ______ neuron.

Answer 3

Anandamine; retrograde signaling; presynaptic; excessive; postsynaptic

Question 4

CB1 receptors are expressed ______ in the ______, but there is an absence of them in the ______, resulting in a ______ risk of ______ ______. CB2 receptors are expressed ______.

Answer 4

centrally; brain; medulla; low; respiratory depression; peripherally

Question 5

Effects of TCH through CB1 receptor agonism (7)

Answer 5

1. Physical relaxation
2. Hyperphagia
3. Tachycardia
4. Decreased coordination
5. Conjunctivitis
6. Minor pain control
7. Mild hallucinations

Question 6

Potential medical uses for CB1 receptor agonists (5)

Answer 6

1. Stimulate appetite in patients with AIDS
2. Reduce seizure frequency in epilepsy
3. Decrease intraocular pressure in glaucoma
4. Treat nausea caused by cancer chemotherapy (dronabinol)
5. Reduce pain (nabilone)

Question 7

Associated effects of CB1 receptor antagonism (2)

Answer 7

1. Negative mood

2. Suicidality

Question 8

Agonism of CB1 receptors in the CNS releases inhibition (disinhibits) ______ signaling in the ______. Signaling then activates the ______, where it causes the sense of “novelty” to sensory stimuli.

Answer 8

Dopaminergic; VTA; amygdala

Question 9

Heavy users of THC have ______-______ of ____ receptors. This leads to symptoms of ______ and a sense of ______. Heavy THC use during adolescence may be linked to ______ ______.

Answer 9

Down-regulation; CB1; amotivation; boredom; reduced IQ

Question 10

THC also reduces ______-______ ______ due to imbalances in ______ in the ______. Chronic THC exposure may ______ the number of ______ ______. THC also causes ______ ______ and impaired ______ ______ control.

Answer 10

short-term memory; GABA; hippocampus; decrease; hippocampal neurons; muscle weakness; skilled motor

Question 11

Symptoms of cannabis intoxication (12)

Answer 11

1. Euphoria, sensory intensification
2. Apathy
3. Fear, anxiety, distrust, or panic
4. Increased appetite
5. Hallucinations
6. Dry mouth
7. Sedation
8. Tachycardia
9. Conjunctival congestion
10. Impaired judgement
11. Impaired motor coordination
12. Social withdrawal

Question 12

Cannabis Pharmacokinetics (7)

Answer 12

1. Effects of smoked/inhaled marijuana occur rapidly (sec-min), with maximum effects observed in 1-2 hours
2. Oral administration (food or drink) has slower onset, but longer lasting effects
3. Half-life = 4.5 hours
4. Metabolized by CYP450 and glucuronidation
5. THC distributes in adipose tissue
6. “Reservoir” of THC, slowly releases into bloodstream; can be detected in the urine up to 4-5 weeks after last use in heavy users
7. Withdrawal occurs much later in heavy users

Question 13

Cannabis intoxication (overdose) can occur in accidental over-ingestion and/or unintentional use of high-potency marijuana. Current species now have ____ more THC than 50 years ago. Hashish sample tested ____ THC content. Hashish is concentrated into ______ or ______ ______ ______ (____) and can be administered through e-cigarettes (vaping).

Answer 13

20x; 82.46%; wax; butane honey oil (BHO)

Question 14

Cannabis products used in “dabbing”, like BHO, can have terpene byproducts. Terpenes degrade into methacolein and cause ______ ______ ______. Contaminants in ______ or ______ cartridges have also been linked to ______ ______.

Answer 14

acute lung injury; vaping; e-cigarette; lung disease

Question 15

Cannabis tolerance and withdrawal (4)

Answer 15

1. Tolerance develops rapidly with chronic use and disappears rapidly
2. Withdrawal syndrome develops within a week after sudden cessation of regular (daily) doses over a few months
3. 9% of all users and 17% of adolescent users will develop dependence and experience withdrawal
4. Cannabis/marijuana use disorder has no specific pharmacologic treatments

Question 16

Cannabis withdrawal syndrome symptoms (11)

Answer 16

1. Restlessness
2. Anxiety
3. Irritability
4. Depressed mood
5. Mild agitation
6. Insomnia
7. Sleep EEG disturbances
8. Nausea, cramping
9. Cravings
10. Pain
11. Decreased appetite, weight loss

Question 17

Cannabis Use Disorder Diagnosis (4)

Answer 17

1. *Criteria for cannabis disorder is similar to other substance use disorders.
2. Long-term clinical outcomes may be less severe
3. Impaired behavioral and cognitive functioning may drive treatment seeking
4. Comorbidity with other psychiatric disorders or other substance abuse is common

Question 18

Cannabis Use Disorder Treatments (3)

Answer 18

1. Behavioral treatments show promise: CBT, contingency management, motivational enhancement therapy
2. No pharmacotherapeutic medications are FDA-approved for the treatment of cannabis use disorder
3. Withdrawal symptoms (insomnia, anxiety, depression, etc.) may be treated pharmacologically using agents like zolpidem, buspirone, and gabapentin, respectively

Question 19

Hallucinogens (agents and effects [psychological and physical])

Answer 19

Agents: Lysergic Acid Diethylamide (LSD), MDMA (ecstacy/Molly), and PCP (phencyclidine)

Psychological effects: produces altered states of consciousness and perceptions. Usually pleasurable, but sometimes frightening (“bad trip”). Can also produce effects similar to psychosis (delusions, hallucinations). Elevates mood, impairs memory, reduces attention span, and causes “flashbacks”.

Physical effects: impairment of complex motor activity, cardiovascular symptoms, sweating, tremor, nystagmus (PCP).

Question 20

LSD (general, MOA, effects, ADRs)

Answer 20

General: Synthesized by Albert Hofmann in 1937. LSD-induced psychosis is used to test new antipsychotic agents. Generally not associated with dependence or withdrawal.

MOA: Hallucinogenic effects due to partial agonism of 5-HT2A. Disrupts thalamic gating with sensory overload of the cortex.

Effects: “Mystical experiences, transcendence of time and space, joy, peace”. Mediated through serotonin, dopamine, and norepinephrine.

ADRs: Can induce psychosis in vulnerable subjects. Toxicity events are rare; cardiovascular collapse observed with extremely high doses.

Question 21

Hallucinogen Intoxication Syndrome (4)

Answer 21

1. Changes in perception associated with hallucinogenic effects
2. May last several hours or persist following cessation of substance use
3. Symptoms common to all hallucinogens: pupillary dilation, tachycardia, sweating, palpitations, blurring of vision, tremors, lack of coordination
4. Treatment: supportive counseling, benzodiazepines, antipsychotics

*PCP and MDMA have other toxicity risks.

Question 22

MDMA (general, MOA, effects, ADRs)

Answer 22

General: AKA Ecstasy/Molly. The “club drug” or “rave drug”.

MOA: Increases extracellular concentrations of serotonin by REVERSAL of serotonin transporter function- causes an efflux of serotonin. Marked intracellular 5-HT depletion for 24 hours after a single dose causes depressive symptoms after use.

Effects: Promotes feelings of intimacy and empathy without impairing intellectual capacities. Hallucinogen and stimulant- amphetamine derivative.

ADRs: Neurotoxicity, especially in chronic, heavy users is a concern.

Question 23

MDMA Intoxication, Toxicity, and Withdrawal Symptoms

Answer 23

MDMA intoxication similar to other hallucinogen intoxication symptoms PLUS:

Acute toxicity:

1. Hyperthermia, which can be fatal if coupled with dehydration (excessive water intake to compensate has caused hyponatremia, seizures, and death)
2. Serotonin syndrome
3. Seizures

Withdrawal is associated with depression that can last several weeks. Increased aggression can occur during periods of abstinence in chronic MDMA users due to depleted serotonin.

Question 24

PCP (general, MOA, effects)

Answer 24

General: AKA “angel dust” or “special K”. Labelled the “most dangerous drug in America” in the 1970s. Originally developed as a new anesthetic. Appears as a contaminant/additive in many illicit drugs, including marijuana.

MOA: Antagonist of NMDA receptors, induces psychotic symptoms. Supports glutamatergic hypothesis of schizophrenia.

Effects: Causes dissociation, emotional withdrawal, bizarre responses to stimuli, catatonia

Question 25

PCP Intoxication Syndrome, Treatment, and other Toxic Events

Answer 25

1. Belligerence, assaultiveness, impulsiveness, impaired judgement
2. Nystagmus (vertical or horizontal)
3. Numbness or blunted pain response
4. Ataxia
5. Dysarthria - slurred speech
6. Muscle rigidity
7. Seizures or coma
8. Hyperacusis - increased sensitivity to certain frequencies and volumes of sound

Treatment:

1. Non-stimulating environment
2. Restraints
3. Acidification or urine to increase elimination (Vitamin C)
4. Antipsychotics

Toxic Events:

1. Cardiovascular toxicity (cardiac arrest)
2. Neurological toxicity
3. Rhabdomyolysis and hyperthermia

*No pharmacotherapeutic interventions for toxicity

Question 26

PCP Use Disorder (5)

Answer 26

1. *Criteria for PCP and other hallucinogen use disorders are similar to other substance use disorders
2. Psychotomimetic effects of hallucinogens may be MISTAKEN for schizophrenia or amphetamines
3. PCP appears in urine samples up to 8 days after ingestion
4. Withdrawal signs and symptoms associated with PCP use disorder have not been documented
5. Treatment focuses on education and prevention