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Pmcol 305 > Hallucinogens > Flashcards

Hallucinogens Flashcards

1
Q

sources of hallucinogens

A

fungi
animal
plants

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2
Q

claviceps purpurea

A

fungus
→ lysergic acid

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3
Q

psilocybin source

A

from psilocybe, panaeolus, conocybe species

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4
Q

amanita muscaria

A

fungi
fly agaric
→ ibotenic acid and muscimol

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5
Q

animal sources

A

colorado river toad
→ bufotenin

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6
Q

ipomoea nil

A

seeds → LA amide (LAA; ergine)

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7
Q

lophophora williamsii

A

(plant)
peyote
→ mescaline

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8
Q

ayahuasca source + chemicals

A

made from psychotria viridis + banisteriopsis caapi vines
→ N,N-dimethyltryptamine (DMT), harmine, harmaline

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9
Q

anadenanthera peregrine + virola trees

A

DMT and bufotenin

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10
Q

atropa belladonna
datura
henbane
mandrake

A

atropine
scopolamine
hyoscyamine

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11
Q

tabernanthe iboga roots

A

ibogaine

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12
Q

myristica fragrans

A

(nutmeg and mace)
→ myristicin, elemicin

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13
Q

DMT sources

A

anadenanthera peregrine + virola trees
psychotria viridis and banisteriopsis caapi vines

chemical in ayahuasca

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14
Q

bufotenin sources

A

colorado river toad
anadenanthera peregrine + virola trees

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15
Q

indoleamine nucleus

A

benzene + pyrrole ring
similarity to 5HT (+ tryptophan)

ibogaine, harmine, DMT, bufotenin, psilocybin, LSD, LA

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16
Q

phenethylamine nucleus

A

phenol + ethyl + amine

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17
Q

catechol nucleus

A

benzene + 2 OH

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18
Q

DA

A

phenethylamine + catechol

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19
Q

NE

A

phenethylamine + catechol + OH

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20
Q

mescaline

A

phenethylamine + catechol
+ ether

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21
Q

dissociative drugs

A

ketamine
ibotenic acid
phencyclidine
muscimol

PCP

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22
Q

deliriant drugs

A

atropine
hyoscyamine
scopolamine

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23
Q

psychedelic drugs

A

lysergic acid amide
mescaline
DMT
bufotenin
psilocybin

LSD
MDMA

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24
Q

medical uses

A

set and setting are foundational
not all hallucinogens are safe

cluster headaches

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25
Q

cluster headaches

A

dilated vessels

LSD - elevated 5HT-induced vasoconstriction

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26
Q

psychedelic effects

A

vivid sensations
altered perceptions and reality
users are responsive + communicative

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27
Q

deliriant effects

A

vivid, confusing fantasy

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28
Q

dissociative effects

A

analgesia
amnesia
catalepsy
detached reality

loss of sensory input

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29
Q

hallucination

A

experience involving perception of something that is not present

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30
Q

illusion

A

altered and distorted perceptions, thoughts, feelings, insights, awareness

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31
Q

delusion

A

fixed belief, unchanged by conflicting evidence

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32
Q

trips

A

dependent on mindset and setting
mindset - expectation, experience, and personality

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33
Q

EC50

A

LSD = high potency
mescaline = low potency

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34
Q

prototypical psychedelic

A

LSD
affects frontal cortex - thought + perception; locus coeruleus + thalamus
5HT 2a receptor

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35
Q

administration of LSD

A

ingested
injected
inhaled
transdermal

10-300 ug

blotting paper, sugar cube, gel caps, pressed tablets, microdots

36
Q

microdosing

A

sub-psychedelic amounts
primarily LSD (5-20ug) and psilocybin (1-2mg)
beneficial effects on mood, creativity, outlook (poor studies)

37
Q

absorption

A

ingestion = 90-100% bioavailability

38
Q

distribution

A

30-90 min onset
~1% enters brain
high TI >1000

39
Q

metabolism

A

liver
110-175 min half life
5-12 hr duration (long)
high occupation time at 5HT 2a receptors

40
Q

excretion

A

kidneys
GI tract

1st order kinetics

41
Q

stages of trip

A

after initial onset
1. 0-30 min
2. 30-120 min
3. 3-5 hr

42
Q

0-30 min

A

physiological changes outside the brain
sympathomimetic
dizziness, nausea, muscle trmors, numbness

43
Q

30-120 min

A

alteration of perceptions
rerouting of sensory info by thalamus = cross over of sensations

44
Q

3-5 hr

A

illusions continue
mind/body disconnect

45
Q

acute psychological effects

A

visual hallucinations + illusions
synesthesia
introspection, ego dissolution

46
Q

acute cognitive effects

A

inability to concentrate
impaired judgement
telepathy with animalss

47
Q

behavioural mechanisms

A

animals will not self-administer
evoke effort to stop administrations

= not addictive

48
Q

physiological mechanisms

A

activates D2-like signaling in NAc, striatum (inhibitory)
not rewarding

5HT 2a receptors in LC, mPFC

49
Q

sympathomimetic

A

increase bp
vasoconstriction
sweating
dilated pupils

50
Q

mPFC projection to LC

A

5HT 2a receptors → augment LC response to regular events
novel encoding → decrease fear by changing modulation
= therapeutic - rewrite traumatic memories

51
Q

thalamus

A

routing hub for sensations
mixing of input + output

52
Q

cortex

A

conscious perceptions

53
Q

cellular mechanisms

A

LSD = agonist at 5HT 1a/b, 2a/b/c, 6 and 7
(primarily 2A)

high affinity agonist at D2 receptors (inhibitory) → Gi/o coupled
= aversive conditioning, lack of self-administration

54
Q

5HT receptors

A

GPCRs → biased agonism

2a: high pre-synaptic expression in cortex → perception and information processing centres
controls transcriptional programming
presynaptic in mPFC → neuroplastic changes via glutamate signaling

55
Q

drug receptor conformation

A

high occupation time

LSD fits into pocket - held tightly by conformational change
= much stronger than ergotamine

56
Q

conformational differences between LSD and ergotamine

A

selection of signaling capabilities
biased agonism via 5HT 2a
blocks receptor → favours alterate signaling

57
Q

bias signaling

A

Gaq → PKC and Ca2+ pathways = activated by non-hallucinogenic chemicals
prolonged receptor occupation shifts activation away from Gaq
hallucinogens activate b-arrestin → desensitization/internalization, MAPK pathways

58
Q

no positive reinforcement

A

LSD is low on abuse potential scale

exception: deliriants

59
Q

muscarinics

A

deliriants - anti-cholinergics

M2/4 = Gi/o linked
M5 = Gq linked → elevates intracellular Ca2+

60
Q

psilocybin

A

ingested - 3-6 hr duration
milder version of LSD
no flashbacks, not lethal
metabolized to psilocin in gut and liver
5HT 2a agonist
sympathomimetic, altered time + perceptions, hallucinations, heightened emotions
not addictive; rapid tolerance

61
Q

DMT

A

snort, smoke, inject
destroyed in the gut - antimicrobial (treat worms, parasites)
short duration - 30-60 min
5HT 2a/c, 1a agonist
no tolerance
similar physiological effects to LSD, psilocybin
psychological effects - intense, vivid hallucination, emotions, introspection, ego dissolution

62
Q

harmine + harmaline

A

B-carboline chemicals
selective and reversible monoamine oxidase-A inhibitors
acetylcholinesterase inhibitors → treat Alzheimer’s disease
stimulate striatal DA release at high doses → treat Parkinson’s disease

63
Q

Ayahuasca

A

DMT + b-carbolines

MAO inhibitors protect DMT from degradation = enhanced distribution to brain
activates vision and memory brain regions
visions, intense emotions, introspection
adverse effects: vomiting, diarrhea

64
Q

bufotenin

A

close chemical similarity to 5HT
common effects: drooling, heart palpitations, elevated bp, O2 depletion, cramped muscles, blurred vision, headache

hallucinations caused by decreased O2 to optic nerve

toads produce toxic glycosides too → dysrhythmias

65
Q

ibogaine

A

block addiction circuits
elevate glial cell line-derived neutrotrophic factor in midbrain (VTA) → reduces cravings and drug intake
risks: damage to cerebellum, severe motor tremors, increase risk of heart attack + seizure

66
Q

mescaline

A

ingested
4-12 hr duration
TI 7-30
vivid hallucinations (LSD)
toxic effects - nausea + vomiting
death due to convulsions and respiratory arrest

67
Q

myristin + elemicin catechols

A

resemble mescaline
in nutmeg + mace
ingested, inhaled, insufflated
lower doses - mild hallucinations, disorientation, confusion, feelings of unreality, euphoria
higher doses - hallucinations, nausea + vomiting, persisting unreality

68
Q

5HT 2a expression

A

subcortical nuclei - alters connectivity
perception, memory, attention modulation of hallucinogens

corticostriatothalamocortical feedback loops → gating theory

69
Q

anti-cholinergic plant sources

A

mandrake - mandragora officinarum
atropa belladonna
datura stramonium
hyoscyamus niger

70
Q

mandrake

A

low doses - relieve anxiety, induce sleep
high doses - hallucinations, amnesia, muscular paralysis

71
Q

primary tropane alkaloids

A

atropine
scopolamine
hyoscyamine

high (toxic) doses required for hallucinations
block muscarinic AChRs → dilate pupils, increase heart rate, dry secretions

72
Q

anticholinergics

A

produce hallucinations but alter memory
physiological effects - elevated hr, dry mouth, lack of perspiration, constipation, difficulty urinating
fatal - rapid hr, hyperthermia, asphyxia
no euphoria
prevent ACh-mediated activation

73
Q

dissociatives

A

PCP + ketamine
amanita muscaria, salvia divinorum
detachment from reality

produce reinforcement in animal models but not by DA release in NAc

74
Q

PCP

A

inhaled - smoked
ingested, insufflated, injected
4-8 hr duration
TI 10-15
dose dependent effects
- 5mg - anaesthetic, analgesic, stimulant or depressant, convulsant, hallucinogen
- 10mg - muscle rigidity, loss of pain sensitivity, agitation, mood swings, detachment

blocks NMDARs in cortex + hippocampus
increased synthesis and release of DA - agitation, stimulation, locomotor activity
long lasting effects
toxic doses >20mg

75
Q

ketamine

A

ingested, inhaled, insufflated, injected
15-20 min onset
35-60 min duration
shorter acting than PCP - same effects
blocks NMDARs in cortex + hippocampus
increase synthesis + release of DA → agitation, stimulation, locomotor activity

76
Q

cellular mechanisms of dissociatives

A

block NMDAR ion channel
affect glu, NE, DA, ACh, 5HT

77
Q

dependence on dissociatives

A

moderate risk, mildly reinforcing
PCP self administration in animals
psychological

78
Q

adverse effects of dissociatives

A

psychosis + analgesia → damaging behaviours
ketamine cystitis → arrest bladder cell growth = cell death → bloody urine, pain, incontinence
long term use - memory loss, speech problems, delusional thinking

79
Q

amanita muscaria

A

ingested
30-90 min onset
up to 12 hr duration
withdrawal headaches, amnesia, sleepiness
active chemical is excreted unchanged in urine
alter body perception, euphoria, dizziness, vivid hallucinations
muscle twitches, sweat, salivation, constricted pupils, lowered bp

15 caps = fatal

80
Q

muscimol

A

amanita muscaria
GABA a receptor agonist → most effects

81
Q

ibotenic acid

A

amanita muscaria
binds NMDARs

82
Q

salvia

A

inhaled, chewed
15-120 min duration
mild alteration of consciousness to full psychedelic trip
vivid visuals, sensory + time disturbances, detachment
nausea, slurred speech, chills
high doses - brain lesions

83
Q

salvinorin A

A

1 of 3 non-alkaloid hallucinogens
primary active in salvia
potent kappa opioid receptor agonist
dysphoric effects, anxiety, fear, confusion

84
Q

NPSs

A

new psychoactive substances
chemical alteration of existing hallucinogens

2-C drugs
bromo-dragonfly
NBOM

85
Q

2-C drugs

A

phenethylamine derivatives + halogen
hallucinations, stimulant effects
5HT receptor agonists
adverse effects → seizure, rigidity, lethal

86
Q

bromo-dragonfly

A

benzodifuran
1-3 day duration
binds 5HT 1 and 2a receptos
vasoconstriction via a-adrenergic receptors
similar effects to LSD
narrow therapeutic window = can be fatal

87
Q

NBOM

A

n-benzyl-oxy-methyl drugs
potent 5HT 2a agonists

Pmcol 305 (18 decks)

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