Drugs with abuse potential

Question 1

THC/Cannabis: Epidemiology

Answer 1

Most common abuse in high schoolers
Surpass tobacco usage
M > F

Question 2

THC: Formulations

Answer 2

Traditional Marijuana – 10% THC
Hashish > 10%
Hash Oil – 50%

Question 3

THC: Metabolism

Answer 3

Rapidly metabolized by liver to 11-OH-∆9 -THC, which is highly active in man.
Metabolized to 9-nor-COOH-THC which is inactive.
Metabolites excreted in urine and feces. They are detectable in urine for many days.

Question 4

THC: Pharmacokinetics

Answer 4

Smoked it reaches brain in 15 to 30 seconds.

3-5 times more potent smoked than when ingested
Oral onset of action is about 30 min.

Metabolized and redistributed in fat
Slowly leaves body.
Duration of action 1 to 6 hours

Plasma half-life - 20-50 hours; 20% remains in body after 5 days and is not detectable at 30 days

Question 5

THC: MoA

Answer 5

CB1 receptor: High in cerebellum hippocampus and basal ganglia, low in hypothalamus
CB2 receptor: Peripheral tissue
Negatively coupled to adenylyl cyclase via Gi – Inhibits transmitter release
Affinity for receptor correlates with psychoactive potency of cannabinoid agonists

Question 6

THC: Effects

Answer 6

Euphoria, memory impairment, perceptual/motor alterations

CV (Tachycardia, orthostatic hypotension, angina)

Pulm (Bronchodilation, lung irritant, decrease alveolar macrophage activity, decrease in ciliary function)

Reproductive (Lowers testosterone/sperm, LHRH release decreased (low FSH and LH), prolactin release decreased in females (abnormal menstrual), hazard to marginally fertile)

Psychopathologic (Acute anxiety reaction, transient paranoia, exacerbation of schizophrenia, diffuse acute brain syndrome – clouding of consciousness and memory, perceptual and sleep disorders, amotivational syndrome)

Question 7

THC: Withdrawal

Answer 7

Restlessness, irritability and mild agitation, sleep difficulties, decreased appetite and nausea, craving

Question 8

THC: Medical Indications

Answer 8

Nausea, AIDS wasting syndrome – Dronabinol
MS pain tx. and cancer pain – THC/Cannabidiol mixture in Canada
Weight loss drug – CB1 antagonist, now removed from market

Question 9

K2 or Spice

MoA
Legality/Scheduling

Answer 9

THC-like CB1 agonist activity
Not DEA scheduled

Question 10

PCP/Ketamine: Pharmacokinetics

Answer 10

Rapid/complete absorption
Plamsa T1/2 12 to 24 hours (overdose up to 72 hours)
Hydroxylation and conjugation in liver
Excretion in urine, primarily as biotransformation products

Question 11

PCP/Ketamine: Cardiovascular Effects

Answer 11

Tachycardia
HTN
Potentiation of catecholamines

Question 12

PCP/Ketamine: CNS effects

Answer 12

Ketamine less potent, shorter duration
Small doses – Drunken state with numbness of extremities
Moderate doses – Analgesia and anesthesia
Psychic state – Resembles sensory isolation except sensory impulses reach neocortex
Catalepoid motor phenomenon
Large doses may produce convulsions

Question 13

PCP/Ketamine: MoA

Answer 13

NMDA Antagonist

Question 14

PCP: Overdose

Answer 14

CNS Manifestations: Anxiety, aggression, halucinations, dysphoria, convulsions, delirium
Sympathomimetic: Tachycardia, HTN crisis

Question 15

PCP/Ketamine: Treatment

Answer 15

Vital sign support
Gastric suction
Acidify urine
Diazepam/Anti-HTN agent
Haloperidol

Question 16

LSD - Indoleamine: Pharmacokinetics

Answer 16

Less than 1 % crosses Blood-Brain barrier
Onset -15 to 20 minutes, duration - 12 hours

Question 17

LSD - Indoleamine: Effects

Answer 17

Sympathomimetic - Tachycardia, increased BP, psychomotor stimulation

Sensory and subjective effects
Altered perception - particularly visual
Lability of mood
Impaired judgment

Tolerance and cross tolerance

Question 18

LSD-Indoleamine: Toxicity

Answer 18

Acute reactions
Hallucinations, anxiety, panic and depersonalization.
< than 24 hours
Quiet environment, BDZs for sedation

Flashbacks - days to years later, can be associated with drug use.

Neurotoxicity - 5-HT damage may be associated with phenethylamine type drugs such as MDMA

Question 19

MDMA: Effects

Answer 19

Induces feelings of “well-being and connection”
Altered time perception
Pyschomotor stimulation, restlessness, bruxisim, anorexia, sweating, tremor

Question 20

MDMA: Pharmacokinetics

Answer 20

Typical oral dose 100-150 mg
Onset of action 20 - 40 minutes; duration 3-4 hours

Question 21

MDMA:
Hangover effect
Neurotoxic against which neurons

Answer 21

Hangover - anhedonia
Neurotoxicity - serotonin neurons

Question 22

GHB: Endogenous pharmacology

Answer 22

Found in brain, precursor and metabolite of GABA
May have own receptor
Can be made in body from GBL

Question 23

GHB: Pharmacokinetics

Answer 23

Typical dose about 1 - 1.5 g
Effects last about 3 hours

Question 24

GHB: Effects

Answer 24

Primarily a depressant - induces a state of relaxation and tranquility
Interacts with ethanol
Overdose characterized by drowsiness, ataxia, nausea and vomiting
Higher doses - loss of bladder control, temporary amnesia, clonus and seizures.

Question 25

Salvia Divinorum
Pharmacology
MoA
Pharmacokinetics

Answer 25

Pharmacology: Oral psychedelic
MoA: Kappa opiod agonist
Pharmacokinetics: Short duration of action – 20 to 45

Question 26

Examples of “legal” drugs

Answer 26

Prescription Drugs
OTC drugs containing dextromethorphan

“Bath Salts”
Mephedrone
Stimulants found in Khat
Now scheduled