Hallucinogens

Question 1

What is the inherent rewarding effect of hallucinogens?

Answer 1

Not inherently rewarding; may or may not produce addiction / pleasure etc

No withdrawal / physical dependence at all, generally no increases in DA

Question 2

What are the 5 groups hallucinogens can be assigned to based on structure?

What do hallucinogens do to these synapses in each group?

Answer 2

1) Ach-like: SYNAPSES BLOCKED
2) 5-HT-like: STIMULATED synapses
3) Catecholamine-like: doesn’t say
4) Glu-like: NMDA BLOCKED
5) Opiate-like: Kappa facilitated

Question 3

What synapses do LSD/psilocybin generally stimulate?

Answer 3

5-HT2A synapses

Question 4

How is psychedelic experience generally elicited pharmacodynamically with hallucinogens?

Answer 4

Block cholinergic synapses
Stimulate 5-HT2A
Block NMDA synapses
Facilitate kappa-opiate synapses

Question 5

What type of hallucinogen is scopolamine?
What receptor does it affect?

What are the phenotypic effects?

Answer 5

Anti-cholinergic; blocks muscarinic Ach

Dry mouth, blurred vision, increased heart rate, dilated pupils

(Jimson weed, belladonna)

Question 6

What is the ED50/LD50 of jimson weed? TI?

Answer 6

ED50 = .5mg
LD50 = 4mg

TI = 8

Question 7

What drugs do the 5-HT agonists include?

Answer 7

Mescaline / MDMA, LSD/psilocybin

Question 8

What receptor does belladonna / jimson weed (scopolamine) effect?

Answer 8

Muscarinic Ach receptor

Question 9

What type of hallucinogen (pharmacodynamic) is mescaline?

Answer 9

5-HT agonist

Question 10

What is an unpleasant phenotypic effect of mescaline?

Answer 10

Vomiting (even experienced users)

Effect in the stomach

Question 11

What is the solubility like for mescaline?

Answer 11

Water soluble, not very lipid soluble

Question 12

What neurotransmitter is mescaline structurally similar to?

Answer 12

NE

Question 13

How long does it take for mescaline to reach peak CNS levels?

Answer 13

1-2hr

Question 14

What is the state in the frontal lobes that hallucinogens cause called?

(Specifically right frontal lobe)

Answer 14

‘Hyperfrontal’ state

Hyperactive right frontal lobe; taking info in more

Question 15

What neurotransmitter is Psilocybin similar to?

Answer 15

5-HT

Question 16

What dose is psilocybin generally taken at? What is the half-life?

Answer 16

0.25mg/kg; effects within 30min, last 2-6hr; half-life of 3hr

Question 17

What is the solubility of psilocybin like?

Answer 17

Quite water-soluble

Question 18

What enzyme breaks down psilocybin?

Answer 18

MAO

Question 19

What is the TI of psilocybin?

Answer 19

Lethal dose in humans unknown, TI quite high. Estimated 4 digits

Question 20

What class of hallucinogens has the smallest TI?

Answer 20

Anti-cholinergics

Question 21

What is the potency of LSD?

Answer 21

Incredibly potent; normal dose is barely visible

Question 22

What dose is generally taken for LSD?

Answer 22

25-300 micrograms (1x10^-6 g)

Question 23

How easily is LSD absorbed?

Answer 23

Readily absorbed, peak levels in 1-3hr

Question 24

Where is LSD metabolized?

Answer 24

Liver, lasts 6-8hr

Question 25

What is the TI of LSD?

Answer 25

280 (very high) But the ED50 is super low, so you still have to be careful

Question 26

What are the effects of LSD?

Answer 26

``` Slowing of time Change in space perception Color perception Synesthesia Hallucinations ```

Question 27

What type of receptors is the locus coeruleus full of?

Answer 27

5-HT2A

Question 28

Why will some monoaminergic neurons have action potentials on their own?

Answer 28

K+ conductance is high Sets up K+ shunt Shunts start to shut themselves off Sodium leaks in as this happens You therefore get a spike

Question 29

How often do these self-firing action potentials in monoaminergic neurons fire?

Answer 29

~1/sec ('basal LC activity')

Question 30

What does NE release in the LC do to glutamatergic excitation in postsynaptic neurons?

Answer 30

Enhances response of postsynaptic neurons to excitation

Question 31

Where (according to Aghajanian & Marek) do hallucinations come from?

Answer 31

Hallucinogens inhibit *basal LC* activity This makes these cells more responsive to sensory inputs So, sensory system activity is enhanced

Question 32

What is the ventral striatum involved in doing to experiences?

Answer 32

Adding motivational behavior

Question 33

According to Vollenweider and Geyer, where do hallucinogens come from?

Answer 33

Increased activity between thalamus, cortical regions, and striatum

Question 34

What drugs are the NMDA glutamate antagonists?

Answer 34

PCP | Ketamine

Question 35

What is PCP also an agonist of?

Answer 35

D-2

Question 36

How is PCP usually taken?

Answer 36

Smoked, but can be taken orally / injected. Aversive effects.

Question 37

What is the solubility of PCP?

Answer 37

Fat-soluble | LOTS of depot binding

Question 38

What is the ED50 for PCP?

Answer 38

~1mg/kg dose; LD50 at 70mg/kg

Question 39

What is the TI for PCP?

Answer 39

High double digits

Question 40

What is the LD50 for ketamine?

Answer 40

No known (safer than PCP)

Question 41

What is the solubility of ketamine?

Answer 41

Lipid & water soluble

Question 42

What effect does salvia have on 5-HT2A and NMDA receptors?

Answer 42

No effect

Question 43

What receptors does salvia effect?

Answer 43

kappa-opiate receptors, D2 receptors

Question 44

How fast are the effects of salvia when smoked? How long does it last?

Answer 44

30-60sec, lasts 10 min

Question 45

What is Ayahuasca?

Answer 45

Hallucinogenic beverage from South America Has vines with MAO inhibitors to make it psychoactive

Question 46

How is Ayuhuasca taken into the brain?

Answer 46

Active transport across BBB

Question 47

What is the active ingredient in Ayuhuasca?

Answer 47

DMT

Question 48

How else can DMT be taken?

Answer 48

Smoked; no need for MAO inhibition

Question 49

What brain state do ketamine and PCP produce?

Answer 49

HYPO frontal (as opposed to HYPER frontal) But they still produce hallucinations!

Question 50

What brain state exists in schizophrenics?

Answer 50

Hypofrontal

Question 51

What are two examples of 5-HT agonists?

Answer 51

Catecholamine-like drugs like mescaline or MDMA Also serotonin-like drugs like LSD or psilocybin