Hallucinogens Flashcards
1
Q
sources of hallucinogens
A
fungi
animal
plants
2
Q
claviceps purpurea
A
fungus
→ lysergic acid
3
Q
psilocybin source
A
from psilocybe, panaeolus, conocybe species
4
Q
amanita muscaria
A
fungi
fly agaric
→ ibotenic acid and muscimol
5
Q
animal sources
A
colorado river toad
→ bufotenin
6
Q
ipomoea nil
A
seeds → LA amide (LAA; ergine)
7
Q
lophophora williamsii
A
(plant)
peyote
→ mescaline
8
Q
ayahuasca source + chemicals
A
made from psychotria viridis + banisteriopsis caapi vines
→ N,N-dimethyltryptamine (DMT), harmine, harmaline
9
Q
anadenanthera peregrine + virola trees
A
DMT and bufotenin
10
Q
atropa belladonna
datura
henbane
mandrake
A
atropine
scopolamine
hyoscyamine
11
Q
tabernanthe iboga roots
A
ibogaine
12
Q
myristica fragrans
A
(nutmeg and mace)
→ myristicin, elemicin
13
Q
DMT sources
A
anadenanthera peregrine + virola trees
psychotria viridis and banisteriopsis caapi vines
chemical in ayahuasca
14
Q
bufotenin sources
A
colorado river toad
anadenanthera peregrine + virola trees
15
Q
indoleamine nucleus
A
benzene + pyrrole ring
similarity to 5HT (+ tryptophan)
ibogaine, harmine, DMT, bufotenin, psilocybin, LSD, LA
16
Q
phenethylamine nucleus
A
phenol + ethyl + amine
17
Q
catechol nucleus
A
benzene + 2 OH
18
Q
DA
A
phenethylamine + catechol
19
Q
NE
A
phenethylamine + catechol + OH
20
Q
mescaline
A
phenethylamine + catechol
+ ether
21
Q
dissociative drugs
A
ketamine
ibotenic acid
phencyclidine
muscimol
PCP
22
Q
deliriant drugs
A
atropine
hyoscyamine
scopolamine
23
Q
psychedelic drugs
A
lysergic acid amide
mescaline
DMT
bufotenin
psilocybin
LSD
MDMA
24
Q
medical uses
A
set and setting are foundational
not all hallucinogens are safe
cluster headaches
25
cluster headaches
dilated vessels
LSD - elevated 5HT-induced vasoconstriction
26
psychedelic effects
vivid sensations
altered perceptions and reality
users are responsive + communicative
27
deliriant effects
vivid, confusing fantasy
28
dissociative effects
analgesia
amnesia
catalepsy
detached reality
loss of sensory input
29
hallucination
experience involving perception of something that is not present
30
illusion
altered and distorted perceptions, thoughts, feelings, insights, awareness
31
delusion
fixed belief, unchanged by conflicting evidence
32
trips
dependent on mindset and setting
mindset - expectation, experience, and personality
33
EC50
LSD = high potency
mescaline = low potency
34
prototypical psychedelic
LSD
affects frontal cortex - thought + perception; locus coeruleus + thalamus
5HT 2a receptor
35
administration of LSD
ingested
injected
inhaled
transdermal
10-300 ug
blotting paper, sugar cube, gel caps, pressed tablets, microdots
36
microdosing
sub-psychedelic amounts
primarily LSD (5-20ug) and psilocybin (1-2mg)
beneficial effects on mood, creativity, outlook (poor studies)
37
absorption
ingestion = 90-100% bioavailability
38
distribution
30-90 min onset
~1% enters brain
high TI >1000
39
metabolism
liver
110-175 min half life
5-12 hr duration (long)
high occupation time at 5HT 2a receptors
40
excretion
kidneys
GI tract
1st order kinetics
41
stages of trip
after initial onset
1. 0-30 min
2. 30-120 min
3. 3-5 hr
42
0-30 min
physiological changes outside the brain
sympathomimetic
dizziness, nausea, muscle trmors, numbness
43
30-120 min
alteration of perceptions
rerouting of sensory info by thalamus = cross over of sensations
44
3-5 hr
illusions continue
mind/body disconnect
45
acute psychological effects
visual hallucinations + illusions
synesthesia
introspection, ego dissolution
46
acute cognitive effects
inability to concentrate
impaired judgement
telepathy with animalss
47
behavioural mechanisms
animals will not self-administer
evoke effort to stop administrations
= not addictive
48
physiological mechanisms
activates D2-like signaling in NAc, striatum (inhibitory)
not rewarding
5HT 2a receptors in LC, mPFC
49
sympathomimetic
increase bp
vasoconstriction
sweating
dilated pupils
50
mPFC projection to LC
5HT 2a receptors → augment LC response to regular events
novel encoding → decrease fear by changing modulation
= therapeutic - rewrite traumatic memories
51
thalamus
routing hub for sensations
mixing of input + output
52
cortex
conscious perceptions
53
cellular mechanisms
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
5HT receptors
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
drug receptor conformation
high occupation time
LSD fits into pocket - held tightly by conformational change
= much stronger than ergotamine
56
conformational differences between LSD and ergotamine
selection of signaling capabilities
biased agonism via 5HT 2a
blocks receptor → favours alterate signaling
57
bias signaling
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
no positive reinforcement
LSD is low on abuse potential scale
exception: deliriants
59
muscarinics
deliriants - anti-cholinergics
M2/4 = Gi/o linked
M5 = Gq linked → elevates intracellular Ca2+
60
psilocybin
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
DMT
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
harmine + harmaline
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
Ayahuasca
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
bufotenin
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
ibogaine
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
mescaline
ingested
4-12 hr duration
TI 7-30
vivid hallucinations (LSD)
toxic effects - nausea + vomiting
death due to convulsions and respiratory arrest
67
myristin + elemicin catechols
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
5HT 2a expression
subcortical nuclei - alters connectivity
perception, memory, attention modulation of hallucinogens
corticostriatothalamocortical feedback loops → gating theory
69
anti-cholinergic plant sources
mandrake - mandragora officinarum
atropa belladonna
datura stramonium
hyoscyamus niger
70
mandrake
low doses - relieve anxiety, induce sleep
high doses - hallucinations, amnesia, muscular paralysis
71
primary tropane alkaloids
atropine
scopolamine
hyoscyamine
high (toxic) doses required for hallucinations
block muscarinic AChRs → dilate pupils, increase heart rate, dry secretions
72
anticholinergics
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
dissociatives
PCP + ketamine
amanita muscaria, salvia divinorum
detachment from reality
produce reinforcement in animal models but not by DA release in NAc
74
PCP
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
ketamine
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
cellular mechanisms of dissociatives
block NMDAR ion channel
affect glu, NE, DA, ACh, 5HT
77
dependence on dissociatives
moderate risk, mildly reinforcing
PCP self administration in animals
psychological
78
adverse effects of dissociatives
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
amanita muscaria
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
muscimol
amanita muscaria
GABA a receptor agonist → most effects
81
ibotenic acid
amanita muscaria
binds NMDARs
82
salvia
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
salvinorin A
1 of 3 non-alkaloid hallucinogens
primary active in salvia
potent kappa opioid receptor agonist
dysphoric effects, anxiety, fear, confusion
84
NPSs
new psychoactive substances
chemical alteration of existing hallucinogens
2-C drugs
bromo-dragonfly
NBOM
85
2-C drugs
phenethylamine derivatives + halogen
hallucinations, stimulant effects
5HT receptor agonists
adverse effects → seizure, rigidity, lethal
86
bromo-dragonfly
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
NBOM
n-benzyl-oxy-methyl drugs
potent 5HT 2a agonists
