Hallucinogens

Question 1

What are hallucinogens

Answer 1

Psychoactive agents that causes changes in perception

Question 2

What systems do hallucinogen drugs alter

Answer 2

Changes function of monoaminergic (serotonin) or glutamatergic systems

Question 3

Catecholamines

Answer 3

Dopamine, Noradrenaline, and adrenaline

Question 4

Monoamines

Answer 4

Serotonin

Question 5

What are the 4 classes of hallucinogens

Answer 5

Classical Psychedelics
Dissociative agents
Deliriants
Oneirogens

Question 6

What are Classical Psychedelics

Answer 6

Drugs that cause perception-altering psychedelic effects
Sensory Distortion

Question 7

What are some examples of Classical Psychedelics
What is the mechanism

Answer 7

Examples: LSD, Psilocybin, DMT

Mechanism: Serotonin 5HT2a Receptor

Question 8

Who discovered LSD, how?

Answer 8

Albert Hofmann was trying to create a more stable pure ergot (which were produced by fungus that grow on rye and are used as vasoconstrictor to treat migraines)

Accidental made LSD 25

Question 9

What is LSD

Answer 9

Classical psychedelic that is a partial agonist with a high affinity for 5HT-2a receptors

Question 10

How do we test that 5HT-2a activation causes hallucinations

Answer 10

Testing mice

Transgenic mouse models lack 5HT2a receptors
Wild type mouse models have 5HT2a receptors

When given LSD the wild type will show hallucinogenic like behaviour in the form of head bobs
The transgenic mouse models do not show such results

Question 11

What is the mechanism behind 5HT-2a agonists?
Why are not all of these agonists hallucinogenic

Answer 11

Biased agonism

LSD (Gq) activates phospholipase C resulting in hallucinogenic effects
LHM activates beta-arresting signalling resulting in non-hallucinogenic effects

Question 12

Ketanserin

Answer 12

5HT-2a antagonist blocks hallucinogenic effect of LSD

Question 13

What is HPPD

Answer 13

Hallucinogenic persisting perception disorder

Distressing visual hallucinations that appear following drug use and even after drug is cleared from system

Question 14

Relation between LSD and tolerance

Answer 14

Taking LSD can lead to downregulation of specifically 5-HT receptors causing tolerance

Thus, if you were to take more LSD or other hallucinogens acting at serotonin receptors they would be less effective

Question 15

Psilocybin

Answer 15

Prodrug converted from psilocybin –> psilocin

Partial agonist with lower affinity for 5HT-2a (Hallucinations)
And grater affinity at 5HT-2b and 5HT-2c

Question 16

What are Dissociative Hallucinogens

Answer 16

Drugs that distort perception of sight and sound and cause detachment from environment/self
Associated with analgesia
Detachment of Self

Question 17

Phencyclidine

Answer 17

NMDA receptor antagonist

Inhibitor of dopamine transporter (DAT)
Increases dopamine within synapse due to lack of clearing ability
Liable for addiction

Question 18

What was phencyclidine advertised as? Why is it not used nowadays

Answer 18

Anesthetic medicine

Liable for addiction and produces paranoia, depersonalization, alters mood states (detached and aggressive)

Question 19

What are Deliriant Hallucinogens

Answer 19

Drugs that cause extreme confusion and inability to control actions, low lucidity
Real feeling hallucinations

Different from Classical as deliriant hallucinogens produce not just visual/auditory hallucinations but the user is not aware they are in a drug-like state

Question 20

What is the mechanism of Deliriant Hallucinogens

Answer 20

Block muscarinic acetylcholine receptors (anticholinergic)

Question 21

Scopolamine

Answer 21

Found in Datura stramonium

Competitive antagonist at muscarinic cholinergic receptors

Question 22

Atropine

Answer 22

Found in Datura stramonium

Competitive antagonist at muscarinic cholinergic receptors

Question 23

Datura stramonium

Answer 23

Contains scopolamine and atropine

Causes delirium, confusion, loss of consciousness, and hallucinations

Systemic effects: Dry mouth, dilated pupils, muscle stiffness, increased heart rate
Lethal at high doses

Question 24

What type of hallucinations can first generation anti-histamines produce

Effect on older people

Answer 24

Deliriant hallucinoigens

Caused by their anticholinergic effects

Older adults are more susceptible to the delirium effects of first-generation antihistamines and should avoid them

Question 25

What are Oneirogens

Answer 25

Drugs that produce a dreamlike state of consciousness

Question 26

Salvinorin A

Answer 26

Active ingridient in Salvia

Agonist at the kappa opioid receptor

Question 27

Effects of Salvinorin A

Answer 27

Produces visual imagery (Classical)
Depersonalization and derealization (Dissociative)
Low lucidity (Delriant)

Defined by immersive dream-like state similar to REM sleep (When dreams occur)

Question 28

Low lucidity

Answer 28

State of impaired awareness of undergoing drug-induced experience

Question 29

Are hallucinogens addictive?

Answer 29

Generally no, except for Phencyclidine (PCP)

Question 30

What is the therapeutic index of classical psychedelics and other hallucinogens

Answer 30

Very safe therapeutic index with little risk of overdose
However, risk of lasting psychological disorders
Other hallucinogens like ketamine have a narrower therapeutic index

Question 31

What are the regulations for the following hallucinogens?

Ketamine
Salvia
LSD

Answer 31

Ketamine = Controlled
Salvia = Unregulated
LSD = Illegal

Question 32

What kind of brain wave rhythm are oneirogens associated with

Answer 32

Kappa opioid receptors agonists are associated with 5Hz theta rhythm, similar to REM sleep

Can induce rapid eye movement even though animal is not asleep