Lecture 20: Hallucinogens Flashcards
What is a Hallucinogen?
A psychoactive agent that causes changes in perception (hallucinations)
Which systems do most hallucinogenic drugs alter the function of?
The monoaminergic or glutamatergic systems
What areas do hallucinogens change?
Thoughts, emotions and consciousness
What does Psychoactive mean?
It has some sort of impact on the brain
Which system of the monoaminergic system do hallucinogens mainly target?
The serotonin system
What is the Criteria for a drug to be classified as a hallucinogen?
- Changes in thought, perception and mood should predominate
- Intellectual or memory impairment should be minimal
- Won’t change arousal level ie put you to sleep or make you super excited
- autonomic nervous system side effects should be minimal
- addictive craving should be minimal
What are Classical Psychedlics?
Drugs with perception altering psychedelic effects
What are examples of Classical Psychedelics?
- LSD
- Psilocybin
- Mescaline
Where is the common mechanism of action of Classical Psychedelics?
At the 5HT2a
What was the potential treatment for early Psychedelics?
Vasoconstrictors as treatment for migraines
Which receptor is the hallucinogenic effects of LSD mediated by?
The 5HT2a receptor
What does LSD do at the 5HT2a receptors?
It is a high affinity partial agonist
Which receptors does LSD target?
5HT2a receptors
What type of agonist is LSD at 5HT2a receptors?
It is a partial agonist with high affinity
How do we know that 5HT2a receptor is responsible for hallucination with LSD?
Transgenic mice with the gene for this receptor knocked out do not show head bob like behaviour when given LSD
Are all 5HT2a agonists hallucinogenic? Provide an example?
No not all 5HT2a agonists are hallucinogenic. LHM binds but does not cause hallucinogenic effect
Why aren’t all 5HT2a agonists hallucinogenic?
Because of biased agonism
Why is LSD hallucinogenic but some 5HT2a agonists arent?
Because LSD activates phospholipase A2 instead of phospholipase C like serotonin does
What does pretreatment with a 5HT2a antagonist do?
Ketanserin blocks hallucinogenic effects of LSD
What are the effects of LSD other than hallucinogens?
- Dilated pupils
- increase heart rate and blood pressure
- Distortion of sensory perception
- Hallucinations ranging from simple color patterns to more complex scenes
- Feeling of enlightenment
What are the adverse psychiatric effects of LSD?
- Anxiety
- Paranoia
- Delusions
What is Hallucinogen persisting perception disorder (HPPD)?
Distressing visual hallucination that appear following drug
What is the Tolerance like in LSD?
It has a profound tolerance that lasts for several days
Why does LSD have profound Tolerance?
Because of the downregulation of 5-HT2 receptors but not other 5-HT receptors
What does Psilocybin look very similar to?
Serotonin
What is the structure of Psilocybin?
It is an indole molecule (6 membered benzene ring fused to a five membered pyrrole ring) with an amine group
Where is Psilocybin produced?
In magic mushrooms
What are the effects of Psilocybin?
- Euphoria
- Visual and mental hallucinations
- Changes in perception and distorted sense of time
- Spiritual experiences
What kind of drug is Psilocybin?
A prodrug
What is Psilocybin converted to since it is a prodrug?
It is dephosphorylated to psilocin in the body
What kind of Agonist is Psilocybin and at which receptors?
Partial agonist at 5HT receptors
High affinity for the 5HT-2b and 5HT2c receptors
Lower affinity at the 5HT2a receptor
At which receptor are the psychedelic effects of Psilocybin?
5-HT2a like LSD
What do dissociative hallucinogens do?
Distort perception of sight and sound and produce feelings of detachment from the environment or self. Can lead to depersonalization
What are dissociative hallucinogens associated?
Analgesia
What kind of Hallucinogen in Phencyclidine (angel dust)?
A dissociative hallucinogen
What does Phencyclidine do at the receptor?
It is an NMDA receptor antagonist
How does Phencyclidine affect the Dopamine transporter?
It inhibits the DAT so there are increased synaptic levels of Dopamine
What is addiction like in Phencyclidine?
It is actually addictive
What was Phencyclidine originally marketed as?
An anesthetic medication but replaced by ketamine
What are the effects of Phencyclidine?
- Changes in body image
- Loss of ego boundaries
- Paranoia and depersonalization
- Altered mood states
What are the other name for Nitrous Oxide?
Laughing gas
What are the effects of Nitrous Oxide?
•Feelings of euphoria after inhalation
What are the targets of Nitrous Oxide?
- Non-competitive NMDA antagonist
- Stimulate endogenous opioid release
- Positive allosteric modulator at GABA-A receptors
What are the effects of Deliriant Hallucinogens?
Induce a state of delirium characterized by extreme confusion and inability to control one’s actions
What is the difference between the effects of Deliriant hallucinogens and psychedelics?
They both produce visual and auditory hallucination but imagery associated with deliriant hallucinogens is often perceived as real and users may not be aware they are in a state of drug altered consciousness
Which receptors do Deliriant Hallucinogens tend to block?
Muscarinic Acetylcholine receptors
Where is Datura stramonium found?
In plants
What does Datura contain?
- Scopolamine
* Atropine
What do atropine and scopolamine do at receptors?
They are competitive antagonists at the muscarinic cholinergic receptors
What are the symptoms of Datura?
- Delirium
- Confusion
- Hallucinations
- Consciousness
- Also has systemic effects
Why are effects of Datura not as restricted to the brain?
Because they target the muscarinic cholinergic system
What can also produce deliriant hallucinations at very high doses?
First generation antihistamines because they can bind to muscarinic receptors
Why can you overdose on Datura?
Because of their cholinergic effects
