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Lecture 20: Hallucinogens Flashcards

1
Q

What is a Hallucinogen?

A

A psychoactive agent that causes changes in perception (hallucinations)

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2
Q

Which systems do most hallucinogenic drugs alter the function of?

A

The monoaminergic or glutamatergic systems

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3
Q

What areas do hallucinogens change?

A

Thoughts, emotions and consciousness

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4
Q

What does Psychoactive mean?

A

It has some sort of impact on the brain

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5
Q

Which system of the monoaminergic system do hallucinogens mainly target?

A

The serotonin system

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6
Q

What is the Criteria for a drug to be classified as a hallucinogen?

A
  • 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
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7
Q

What are Classical Psychedlics?

A

Drugs with perception altering psychedelic effects

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8
Q

What are examples of Classical Psychedelics?

A
  • LSD
  • Psilocybin
  • Mescaline
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9
Q

Where is the common mechanism of action of Classical Psychedelics?

A

At the 5HT2a

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10
Q

What was the potential treatment for early Psychedelics?

A

Vasoconstrictors as treatment for migraines

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11
Q

Which receptor is the hallucinogenic effects of LSD mediated by?

A

The 5HT2a receptor

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12
Q

What does LSD do at the 5HT2a receptors?

A

It is a high affinity partial agonist

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13
Q

Which receptors does LSD target?

A

5HT2a receptors

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14
Q

What type of agonist is LSD at 5HT2a receptors?

A

It is a partial agonist with high affinity

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15
Q

How do we know that 5HT2a receptor is responsible for hallucination with LSD?

A

Transgenic mice with the gene for this receptor knocked out do not show head bob like behaviour when given LSD

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16
Q

Are all 5HT2a agonists hallucinogenic? Provide an example?

A

No not all 5HT2a agonists are hallucinogenic. LHM binds but does not cause hallucinogenic effect

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17
Q

Why aren’t all 5HT2a agonists hallucinogenic?

A

Because of biased agonism

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18
Q

Why is LSD hallucinogenic but some 5HT2a agonists arent?

A

Because LSD activates phospholipase A2 instead of phospholipase C like serotonin does

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19
Q

What does pretreatment with a 5HT2a antagonist do?

A

Ketanserin blocks hallucinogenic effects of LSD

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20
Q

What are the effects of LSD other than hallucinogens?

A
  • 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
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21
Q

What are the adverse psychiatric effects of LSD?

A
  • Anxiety
  • Paranoia
  • Delusions
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22
Q

What is Hallucinogen persisting perception disorder (HPPD)?

A

Distressing visual hallucination that appear following drug

23
Q

What is the Tolerance like in LSD?

A

It has a profound tolerance that lasts for several days

24
Q

Why does LSD have profound Tolerance?

A

Because of the downregulation of 5-HT2 receptors but not other 5-HT receptors

25
What does Psilocybin look very similar to?
Serotonin
26
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
27
Where is Psilocybin produced?
In magic mushrooms
28
What are the effects of Psilocybin?
* Euphoria * Visual and mental hallucinations * Changes in perception and distorted sense of time * Spiritual experiences
29
What kind of drug is Psilocybin?
A prodrug
30
What is Psilocybin converted to since it is a prodrug?
It is dephosphorylated to psilocin in the body
31
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
32
At which receptor are the psychedelic effects of Psilocybin?
5-HT2a like LSD
33
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
34
What are dissociative hallucinogens associated?
Analgesia
35
What kind of Hallucinogen in Phencyclidine (angel dust)?
A dissociative hallucinogen
36
What does Phencyclidine do at the receptor?
It is an NMDA receptor antagonist
37
How does Phencyclidine affect the Dopamine transporter?
It inhibits the DAT so there are increased synaptic levels of Dopamine
38
What is addiction like in Phencyclidine?
It is actually addictive
39
What was Phencyclidine originally marketed as?
An anesthetic medication but replaced by ketamine
40
What are the effects of Phencyclidine?
* Changes in body image * Loss of ego boundaries * Paranoia and depersonalization * Altered mood states
41
What are the other name for Nitrous Oxide?
Laughing gas
42
What are the effects of Nitrous Oxide?
•Feelings of euphoria after inhalation
43
What are the targets of Nitrous Oxide?
* Non-competitive NMDA antagonist * Stimulate endogenous opioid release * Positive allosteric modulator at GABA-A receptors
44
What are the effects of Deliriant Hallucinogens?
Induce a state of delirium characterized by extreme confusion and inability to control one's actions
45
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
46
Which receptors do Deliriant Hallucinogens tend to block?
Muscarinic Acetylcholine receptors
47
Where is Datura stramonium found?
In plants
48
What does Datura contain?
* Scopolamine | * Atropine
49
What do atropine and scopolamine do at receptors?
They are competitive antagonists at the muscarinic cholinergic receptors
50
What are the symptoms of Datura?
* Delirium * Confusion * Hallucinations * Consciousness * Also has systemic effects
51
Why are effects of Datura not as restricted to the brain?
Because they target the muscarinic cholinergic system
52
What can also produce deliriant hallucinations at very high doses?
First generation antihistamines because they can bind to muscarinic receptors
53
Why can you overdose on Datura?
Because of their cholinergic effects

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