20 Hallucinogens Flashcards
What is a hallucinogen?
a psychoactive agent that causes changes in thoughts, emotions, and consciousness
- most hallucinogen drugs alter function of the monoaminergic or glutamatergic systems
most hallucinogen drugs alter function of the _______\_or ________\_ systems
most hallucinogen drugs alter function of the monoaminergic (specifically serotonin) or glutamatergic systems
What are five criteria for a drug to be classified as a hallucinogen?
- In proportion to other effects, changes in thought, perception, and mood should predominate
- Intellectual or memory impairment should be minimal
- Stupor, narcosis, or excessive stimulation should not be an integral effect
- autonomic nervous system side effects should be minimal
- addictive craving should be absent = low abuse liability
What are classical psychedelics?
Include drugs with perception-altering psychedelic effects
- eg lysergic acid diethylamide (LSD)
- Psilocybin
- Mescaline
- Common mechanism of action at the serotonin 5HT2a receptor
What is the mechanism of action of classical psychedelics?
Common mechanism of action at the serotonin 5HT2a receptor
- these include drugs with perception-altering psychedelic effects
What drug did Albert Hofmann accidentally discover?
Lysergamides (LSD)
From what was LSD discovered from?
Ergot alkaloids which are produced by a fungus that grows on rye
- known to be good vasoconstrictors - potential treatment for migraine
- Pure ergot derivative not very stable in solution so Hofmann chemically manipulated it to make it more stable
- Ended up making lysergic acid diethylamide (LSD) = highly hallucinogenic
Why do ergot alkaloids have potential for treating migraines?
Good vasocontrictors
LSD has over _______ known targets including several _____ receptors
Remember: Low Ki = _____ affinity
LSD has over 50 known targets including several serotonin (5-HT) receptors
Remember: Low Ki = high affinity
LSD has the highest affinity for the _______ receptors
Serotonin
The hallucinogenic effects of LSD is mediated by ______ receptor
The hallucinogenic effects of LSD is mediated by 5HT-2a receptor
- LSD is a high affinity partial agonist at 5-HT2a receptors
How do we know 5HT-2a activation is responsible for hallucinations?
Transgenic mouse model lacking these receptors (5HT-2a knockout mice) do not show hallucinogenic like behavior to LSD
Are all 5HT-2a agonists hallucinogenic?
No
Why aren’t all 5HT-2a agonists hallucinogenic?
biased mechanism
- LSD activates phospholipase A2 instead of phospholipase C (like serotonin)
- Leads to different intracellular signalling pathways and regulation of different genes
What drug blocks the hallucinogenic effects of LSD in humans? How?
Ketanserin
- antagonist of 5HT2a
**In image should say LSD + ketanserin*** (NOT KETAMINE)
LSD effects:
- ____ pupils, ______ heart rate and blood pressure
- disortion of ______ perception
- sometimes feeling of _______
- Adverse psychiatric effects such as _____, _____ and ______
LSD effects:
- dilated pupils, increased heart rate and blood pressure
- disortion of sensory perception
- sometimes feeling of enlightenment/euphoria - leading to exploration of microdosing for mental illness
- Adverse psychiatric effects such as anxiety, paranoia, and delusions - can be deadly
What is Hallucinogen persisting perception disorder?
Distressing visual hallucinations that appear following drug use
Single dose of LSD can lead to profound _____ that lasts for several days and is accompanied by the downregulation of _____ receptors but NOT _____ receptors
Single dose of LSD can lead to profound tolerance that lasts for several days and is accompanied by the downregulation of 5-HT2 receptors but NOT other 5-HT receptors
Crosstolerance of LSD with other hallucinogens acting at the ______ receptors can occur. Examples include ____ and ____
Cross tolerance of LSD with other hallucinogens acting at the serotonin receptors can occur. Examples include DMT and Psilocybin
What is psilocybin?
Like LCD, acts at the serotonin system = structural homology to serotonin
- indole molecule (6-membered benzene ring fused to a five membered pyrrole ring) with an amine group
Psilocybin is a naturally occurring hallucinogen compound produced by _______
when ingested causes _____, ______, changes in ______ and distorted sense of _____
Adverse reactions: ____ and _____
Psilocybin is a naturally occurring hallucinogen compound produced by psilocybin mushrooms
when ingested causes euphoria, visual and mental hallucinations changes in perception and distorted sense of time, spiritual experiences
Adverse reactions: panic attacks and nausea
Psilocybin is produced by psilocybin mushrooms as a ______
Psilocybin is produced by psilocybin mushrooms as a prodrug
Psilocybin is a prodrug that is rapidly dephosphorylated to ____ in the body
Psilocybin is a prodrug that is rapidly dephosphorylated to psilocin in the body
Psilocin is a _________ at 5HT receptors
Psilocin is a partial agonist at 5HT receptors
- High affinity for the 5HT-2b and 5HT-2c receptors
- Low affinity at the 5HT-2a receptor
- Psilocin is a partial agonist at 5HT receptors
- High affinity for the ____\_and ____\_ receptors
- Low affinity at the ____\_ receptor
- Psilocin is a partial agonist at 5HT receptors
- High affinity for the 5HT-2b and 5HT-2c receptors
- Low affinity at the 5HT-2a receptor
The hallucinogenic effects of psilocybin are from activation of the ______ receptor (same as LSD)
The hallucinogenic effects of psilocybin are from activation of the 5-HT2a receptor (same as LSD)
What are dissociative hallucinogens?
Distort perception of sight and sound and produce feelings of detachment from the environment or self
Can lead to depersonalization (out of body experiences
Often associated with analgesic
What is phencyclidine?
A dissociative hallucinogen
aka angel dust
- is an NMDA receptor antagonist (like ketamine)
- Acts as an inhibitor at the dopamine transporter (DAT) so increases synaptic levels of dopamine
- one of the few hallucinogenic drugs that are self-administered in animals (addiction liability)
phencyclidine is a ________\_
aka angel dust
- is an ________\_ (like ketamine)
- Acts as an inhibitor at the ________\_ (DAT) so increases synaptic levels of dopamine
- one of the few hallucinogenic drugs that are self-administered in animals (addiction liability)
phencyclidine is a dissociative hallucinogen
aka angel dust
- is an NMDA receptor antagonist (like ketamine)
- Acts as an inhibitor at the dopamine transporter (DAT) so increases synaptic levels of dopamine
- one of the few hallucinogenic drugs that are self-administered in animals (addiction liability)
Phencyclidine was initially marketed as an _____ medication, has since been replaced by ketamine
Phencyclidine was initially marketed as an anesthetic medication, has since been replaced by ketamine
WHat is nitrous oxide?
Dissociative hallucinogen
aka laughing gas
Nitrous oxide is a commonly prescribed ________
- leads to feelings of _____ and ______ after inhalation
- Low ______
- Multiple targets in the brain:
Nitrous oxide is a commonly prescribed dissociative anesthetic
- leads to feelings of euphoria and depersonalization after inhalation
- Low potency
- Multiple targets in the brain:
- non-competitive NMDA antagonist
- stimulate endogenous opioid release
- positive allosteric modulator at GABA-A receptors
What are three targets of Nitrous Oxide in the brain?
Multiple targets in the brain:
- non-competitive NMDA antagonist
- stimulate endogenous opioid release
- positive allosteric modulator at GABA-A receptors
Analgesic of nitrous oxide may be due to release of _____ and activation of ______
Analgesic of nitrous oxide may be due to release of dynorphin and activation of kappa-opioid receptor
What are deliriant hallucinogens
Induce a state of delirium characterized by extreme confusion and inability to control ones actions
- both deliriant hallucinogens and psychedelics (like LSD) can produce visual and auditory hallucinations
- Difference is with deliriant hallucinogens the user has low lucidity (thinks what’s happening is real)
- user lacks the metacognitive capacity to identify the experience and its content as a dream
Deliriant hallucinogens tend to block ______
Deliriant hallucinogens tend to block muscarinic acetylcholine receptors (anticholinergic)
What is an example of deliriant hallucinogens?
- Datura stramonium is a widespread poisonous plant that contains tropane alkaloids such as:
- Scopolamine
- Atropine
- These are competitive antagonists at the muscarinic cholinergic receptors
- symptoms include delirium, confusion, hallucinations and loss of consciousness
- dry mouth, dilated pupils, muscle stiffness, tachycardia
- lethal at high doses
First generation anti-histamines (like ______) can produce ________ at very high doses because of their _________ effects
First-generation antihistamines (like diphenhydramine) can produce deliriant hallucinations at very high doses because of their anticholinergic effects
