Psychedelic Drugs

Question 1

Psychedelics

Answer 1

Class of psychoactive substances that produce
changes in perception, mood and cognition (as well as physiological changes). The term psychedelic literally means “mind expanding.”

Classical psychedelics are relatively safe in comparison to other ‘street drugs.’ Psychedelics show some promise as theraputic agents.

Question 2

US Controlled Substances Act

Answer 2

Classified drugs into 5 schedules depending on the potential for abuse. (Schedule V is lowest, Schedule I is highest)

Alcohol and THC are not scheduled in Canada

Question 3

Classical (Serotonergic) Psychedelics

Answer 3

Psilocybin, LSD, DMT, Mescaline
Structural similarities to serotonin
Partial agonists
Activate serotonin 5-HT2A receptors as a primary mechanism
Activate other subtypes of serotonin (5-HT) receptors as well

Question 4

Which serotonin receptors are ionotropic, which are metabotropic? Especially important to know 5-HT(2A)

Answer 4

All serotonin receptors are metabotropic except for 5-HT(3), which is ionotropic. Thus classical psychedelics primarily function on the metabotropic 5-HT(2A) receptors.

Question 5

Head-twitch response

Answer 5

When psychedelics are administered, the rodent “head twitch” increases. High predictive validity for effects in humans

Question 6

Classical Psychedelics

Activation of 5HT2A Receptor Signaling

Answer 6

• Canonical signalling pathway
• Excitatory,

Come back to this later :(

Question 7

Non-Classical Psychedelics

Answer 7

Ketamine, MDMA (molly)
Structurally dissimilar
Don’t activate serotonin 2A receptors as a primary mechanism

Question 8

‘Good’ psychedelic effects

Answer 8

Feelings of transcendence, profoundness, sacredness, positive mood

Question 9

‘Bad’ psychedelic effects

Answer 9

Negative thoughts, loss of control, hallucinations, panic, mood swings, overheating

Question 10

Psilocin (psilocybin)

Answer 10

The psychoactive constituent in hallucinogenic (“magic”) mushrooms of the Psilocybe genus. Causes visual hallucinations.

Question 11

Lysergic Acid Diethylamine (LSD)

Answer 11

A highly potent classical psychedelic drug.

Question 12

LSD reaches peak absorption after:

Answer 12

60 minutes

Question 13

Half-life of LSD, and how long its pharmalogical effects can last

Answer 13

Half-life: 3 hours
Effects can last as long as: 8 hours

Question 14

N,N-dimethyl tryptamine (DMT)

Answer 14

Hallucinogenic compound found in certain South American plants and produced in small amounts endogenously (within the body). DMT appears to serve as an agonist for sigma-1 receptors.

Question 15

Mescaline

Answer 15

Found in the peyote cactus. Causes visual hallucinations.

Question 16

Ketamine

Answer 16

A non-classical psychedelic, a dissociative anesthetic. Low-dose ketamine has robust antidepressant effects with a single dose (hrs to weeks). Has shown potential for transdiagnostic issues too (PTSD, substance use disorder, pain).

Question 17

MDMA (aka Molly or Ecstasy)

Answer 17

• Mixed stimulant-psychedelic drug used recreationally
• Increases dopamine, serotonin (5HT), and norepinephrine
• Can cause euphoria, hence street name “ecstasy” (note though, that ecstasy does not always refer to MDMA)
• Also called an empathogen because it increases sociability and feelings of empathy
• Shows some efficacy in treatment of PTSD

Question 18

MDMA is absorbed through the [answer] and metabolized in the [answer]

Answer 18

Absorbed through the gastrointestinal tract, and metabolized in the liver

Question 19

Deficiencies in the [answer] enzyme lead to accumulation of MDMA in the body, which prolongs effects of the drug and increases the probability of adverse effects.

Answer 19

CYP2D6 enzyme

Question 20

MDMA’s elimination half-life:

Answer 20

9 hours

Question 21

The two ways that MDMA alters serotonin neurotransmission

Answer 21

1. MDMA inhibits serotonin transportation into synaptic storage vesicles (prevents the storage of serotonin).
2. MDMA reverses serotonin membrane transporters, expelling unstored serotonin that was not catabolized into the synaptic cleft.

Both these mechanisms increase extracellular brain serotonin levels.

Question 22

How MDMA enhances extracellular levels of dopamine in the brain:

Answer 22

MDMA, like amphetamine, inhibits dopamine entry into storage vesicles, and reverses the dopamine membrane transporter direction, allowing higher extracellular levels of dopamine to be present.

Question 23

Chronic administration of MDMA can result in:

Answer 23

Serotonin neuron loss and cognitive deficits

Question 24

Which gender exhibits a greater sensitivity to MDMA?

Answer 24

Women exhibit a greater sensitivity to MDMA.

Question 25

Phencyclidine (PCP)

Answer 25

A dissociative anesthetic also known as *angel dust*. A noncompetitive antagonist for glutamate NDMA receptors. Glutamate can still bind to an NDMA receptor that PCP is binded to, but PCP will prevent ions from passing through the receptor. The most abused dissociative anesthetic. ## Footnote Would be considered a non-classical psychedelic.

Question 26

Phencyclidine's elimination half-life after absorption

Answer 26

18 hours (but can be as long as 51 hours)

Question 27

Phencyclidine pharmacodynamics

Answer 27

Affects serotonin, dopamine, acetylcholine and glutamate neurotransmission Serotonin: Enhances serotonin levels by inhibiting reuptake of serotonin and functioning as a 5-HT2A receptor Dopamine: Enhances dopamine levels by reuptake inhibition, and is a partial agonist for D2 receptors Acetycholine: A non-competitive antagonist for nicotinic receptors and an antagonist for muscarinic receptors Glutamate: Antagonist for glutamate NDMA receptors, interferes with long-term potentiation (memory forming) ## Footnote Also activates opioid kappa receptors

Question 28

Phencyclidine's effects

Answer 28

Depends on the dose: Low doses: Cause CNS depressant effects, a drunken-like state, numbness in fingers and toes Moderate doses: Cause numbness throughout the body, memory impairment, reported out-of-body experiences High doses: Produce psychostimulant effects, cause a "rush," arousal, and sympathetic nervous system activation. High doses can also cause severe adverse effects, like catalepsy (rigidity) and other symptoms similar to schizophrenia

Question 29

Do dissociative anesthetics cause dependence?

Answer 29

They seldom cause dependence due to infrequent dosage. When dependence occurs, it is usually psychological in nature (cravings and/or feeling lethargic and depressed). Dissociative anesthetics rarely produce physical dependence.

Question 30

Dextromethorphan

Answer 30

An opioid receptor drug and cough suppresant that can cause psychedelic effects in high doses. Found in the cough syrup Robitussin, recreational high dosage of dextromethorphan is called *robo-tripping*. ## Footnote Also mentioned in the opioids deck.

Question 31

Salvinorin A/Salvia divinorum

Answer 31

A kappa opioid receptor agonist that causes psychedelic effects.

Question 32

Scopolamine and atropine

Answer 32

Muscarinic receptor antagonists (they block cholinergic receptors in the parasympathetic nervous system). Found in deadly night shade/belladonna.