20 Hallucinogens

Question 1

What is a hallucinogen?

Answer 1

a psychoactive agent that causes changes in thoughts, emotions, and consciousness

• most hallucinogen drugs alter function of the monoaminergic or glutamatergic systems

Question 2

most hallucinogen drugs alter function of the _______\_or ________\_ systems

Answer 2

most hallucinogen drugs alter function of the monoaminergic (specifically serotonin) or glutamatergic systems

Question 3

What are five criteria for a drug to be classified as a hallucinogen?

Answer 3

1. In proportion to other effects, changes in thought, perception, and mood should predominate
2. Intellectual or memory impairment should be minimal
3. Stupor, narcosis, or excessive stimulation should not be an integral effect
4. autonomic nervous system side effects should be minimal
5. addictive craving should be absent = low abuse liability

Question 4

What are classical psychedelics?

Answer 4

Include drugs with perception-altering psychedelic effects

• eg lysergic acid diethylamide (LSD)
  
  • Psilocybin
  • Mescaline
• Common mechanism of action at the serotonin 5HT2a receptor

Question 5

What is the mechanism of action of classical psychedelics?

Answer 5

Common mechanism of action at the serotonin 5HT2a receptor

• these include drugs with perception-altering psychedelic effects

Question 6

What drug did Albert Hofmann accidentally discover?

Answer 6

Lysergamides (LSD)

Question 7

From what was LSD discovered from?

Answer 7

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

Question 8

Why do ergot alkaloids have potential for treating migraines?

Answer 8

Good vasocontrictors

Question 9

LSD has over _______ known targets including several _____ receptors

Remember: Low Ki = _____ affinity

Answer 9

LSD has over 50 known targets including several serotonin (5-HT) receptors

Remember: Low Ki = high affinity

Question 10

LSD has the highest affinity for the _______ receptors

Answer 10

Serotonin

Question 11

The hallucinogenic effects of LSD is mediated by ______ receptor

Answer 11

The hallucinogenic effects of LSD is mediated by 5HT-2a receptor

• LSD is a high affinity partial agonist at 5-HT2a receptors

Question 12

How do we know 5HT-2a activation is responsible for hallucinations?

Answer 12

Transgenic mouse model lacking these receptors (5HT-2a knockout mice) do not show hallucinogenic like behavior to LSD

Question 13

Are all 5HT-2a agonists hallucinogenic?

Answer 13

No

Question 14

Why aren’t all 5HT-2a agonists hallucinogenic?

Answer 14

biased mechanism

• LSD activates phospholipase A2 instead of phospholipase C (like serotonin)
• Leads to different intracellular signalling pathways and regulation of different genes

Question 15

What drug blocks the hallucinogenic effects of LSD in humans? How?

Answer 15

Ketanserin

• antagonist of 5HT2a

**In image should say LSD + ketanserin*** (NOT KETAMINE)

Question 16

LSD effects:

• ____ pupils, ______ heart rate and blood pressure
• disortion of ______ perception
  
  • sometimes feeling of _______
• Adverse psychiatric effects such as _____, _____ and ______

Answer 16

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

Question 17

What is Hallucinogen persisting perception disorder?

Answer 17

Distressing visual hallucinations that appear following drug use

Question 18

Single dose of LSD can lead to profound _____ that lasts for several days and is accompanied by the downregulation of _____ receptors but NOT _____ receptors

Answer 18

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

Question 19

Crosstolerance of LSD with other hallucinogens acting at the ______ receptors can occur. Examples include ____ and ____

Answer 19

Cross tolerance of LSD with other hallucinogens acting at the serotonin receptors can occur. Examples include DMT and Psilocybin

Question 20

What is psilocybin?

Answer 20

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

Question 21

Psilocybin is a naturally occurring hallucinogen compound produced by _______

when ingested causes _____, ______, changes in ______ and distorted sense of _____

Adverse reactions: ____ and _____

Answer 21

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

Question 22

Psilocybin is produced by psilocybin mushrooms as a ______

Answer 22

Psilocybin is produced by psilocybin mushrooms as a prodrug

Question 23

Psilocybin is a prodrug that is rapidly dephosphorylated to ____ in the body

Answer 23

Psilocybin is a prodrug that is rapidly dephosphorylated to psilocin in the body

Question 24

Psilocin is a _________ at 5HT receptors

Answer 24

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

Question 25

* Psilocin is a *partial agonist* at **5HT receptors** * High affinity for the _\_\_\_\_\__and _\_\_\_\_\__ receptors * Low affinity at the _\_\_\_\_\__ receptor

Answer 25

* 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

Question 26

The hallucinogenic effects of psilocybin are from activation of the ______ receptor (same as LSD)

Answer 26

The hallucinogenic effects of psilocybin are from activation of the _5-HT2a_ receptor (same as LSD)

Question 27

What are dissociative hallucinogens?

Answer 27

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

Question 28

What is phencyclidine?

Answer 28

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)

Question 29

**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)

Answer 29

**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)

Question 30

Phencyclidine was initially marketed as an _____ medication, has since been replaced by ketamine

Answer 30

Phencyclidine was initially marketed as an _anesthetic_ medication, has since been replaced by ketamine

Question 31

WHat is nitrous oxide?

Answer 31

Dissociative hallucinogen aka laughing gas

Question 32

Nitrous oxide is a commonly prescribed \_\_\_\_\_\_\_\_ * leads to feelings of _____ and ______ after inhalation * Low \_\_\_\_\_\_ * Multiple targets in the brain:

Answer 32

Nitrous oxide is a commonly prescribed _dissociative anesthetic_ * leads to feelings of _euphoria_ and _depersonalization_ after inhalation * Low _potency_ * Multiple targets in the brain: 1. non-competitive NMDA antagonist 2. stimulate endogenous opioid release 3. positive allosteric modulator at GABA-A receptors

Question 33

What are three targets of Nitrous Oxide in the brain?

Answer 33

Multiple targets in the brain: 1. non-competitive NMDA antagonist 2. stimulate endogenous opioid release 3. positive allosteric modulator at GABA-A receptors

Question 34

Analgesic of nitrous oxide may be due to release of _____ and activation of \_\_\_\_\_\_

Answer 34

Analgesic of nitrous oxide may be due to release of _dynorphin_ and activation of _kappa-opioid receptor_

Question 35

What are deliriant hallucinogens

Answer 35

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

Question 36

Deliriant hallucinogens tend to block \_\_\_\_\_\_

Answer 36

Deliriant hallucinogens tend to block _muscarinic acetylcholine receptors_ (anticholinergic)

Question 37

What is an example of deliriant hallucinogens?

Answer 37

* 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

Question 38

First generation anti-histamines (like \_\_\_\_\_\_) can produce ________ at very high doses because of their _________ effects

Answer 38

First-generation antihistamines (like _diphenhydramine_) can produce _deliriant hallucinations_ at very high doses because of their _anticholinergic_ effects