Hallucinogens Flashcards
What are hallucinogens
Psychoactive agents that causes changes in perception
What systems do hallucinogen drugs alter
Changes function of monoaminergic (serotonin) or glutamatergic systems
Catecholamines
Dopamine, Noradrenaline, and adrenaline
Monoamines
Serotonin
What are the 4 classes of hallucinogens
Classical Psychedelics
Dissociative agents
Deliriants
Oneirogens
What are Classical Psychedelics
Drugs that cause perception-altering psychedelic effects
Sensory Distortion
What are some examples of Classical Psychedelics
What is the mechanism
Examples: LSD, Psilocybin, DMT
Mechanism: Serotonin 5HT2a Receptor
Who discovered LSD, how?
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
What is LSD
Classical psychedelic that is a partial agonist with a high affinity for 5HT-2a receptors
How do we test that 5HT-2a activation causes hallucinations
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
What is the mechanism behind 5HT-2a agonists?
Why are not all of these agonists hallucinogenic
Biased agonism
LSD (Gq) activates phospholipase C resulting in hallucinogenic effects
LHM activates beta-arresting signalling resulting in non-hallucinogenic effects
Ketanserin
5HT-2a antagonist blocks hallucinogenic effect of LSD
What is HPPD
Hallucinogenic persisting perception disorder
Distressing visual hallucinations that appear following drug use and even after drug is cleared from system
Relation between LSD and tolerance
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
Psilocybin
Prodrug converted from psilocybin –> psilocin
Partial agonist with lower affinity for 5HT-2a (Hallucinations)
And grater affinity at 5HT-2b and 5HT-2c
What are Dissociative Hallucinogens
Drugs that distort perception of sight and sound and cause detachment from environment/self
Associated with analgesia
Detachment of Self
Phencyclidine
NMDA receptor antagonist
Inhibitor of dopamine transporter (DAT)
Increases dopamine within synapse due to lack of clearing ability
Liable for addiction
What was phencyclidine advertised as? Why is it not used nowadays
Anesthetic medicine
Liable for addiction and produces paranoia, depersonalization, alters mood states (detached and aggressive)
What are Deliriant Hallucinogens
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
What is the mechanism of Deliriant Hallucinogens
Block muscarinic acetylcholine receptors (anticholinergic)
Scopolamine
Found in Datura stramonium
Competitive antagonist at muscarinic cholinergic receptors
Atropine
Found in Datura stramonium
Competitive antagonist at muscarinic cholinergic receptors
Datura stramonium
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
What type of hallucinations can first generation anti-histamines produce
Effect on older people
Deliriant hallucinoigens
Caused by their anticholinergic effects
Older adults are more susceptible to the delirium effects of first-generation antihistamines and should avoid them
What are Oneirogens
Drugs that produce a dreamlike state of consciousness
Salvinorin A
Active ingridient in Salvia
Agonist at the kappa opioid receptor
Effects of Salvinorin A
Produces visual imagery (Classical)
Depersonalization and derealization (Dissociative)
Low lucidity (Delriant)
Defined by immersive dream-like state similar to REM sleep (When dreams occur)
Low lucidity
State of impaired awareness of undergoing drug-induced experience
Are hallucinogens addictive?
Generally no, except for Phencyclidine (PCP)
What is the therapeutic index of classical psychedelics and other hallucinogens
Very safe therapeutic index with little risk of overdose
However, risk of lasting psychological disorders
Other hallucinogens like ketamine have a narrower therapeutic index
What are the regulations for the following hallucinogens?
Ketamine
Salvia
LSD
Ketamine = Controlled
Salvia = Unregulated
LSD = Illegal
What kind of brain wave rhythm are oneirogens associated with
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
