Hallucinogens Flashcards
1
Q
What are the sources of hallucinogens?
A
Fungi
Animals
Plants
2
Q
What are forms of fungi hallucinogens?
A
Claviceps purpurea fungus = lyseric acid
200 Psilocybe, Panaeolus, Conobye species = psilocybin
Amanita muscaria = ibotenic acid and muscimol
3
Q
What is the hallucinogen derived from an animal?
A
Colorado river toad = bufotenin
4
Q
What forms of hallucinogens come from plants?
A
LA amide
Mescaline
N,N-dimethyltryptamine, harmine, harmaline
DMT, bufotenin
Atropine, scopolamine, hyoscyamine
Ibogaine
Myristicin, elemicin
5
Q
What drug is derived from Ipomoea nil seeds?
A
LA amide
6
Q
What drug is derived from Lophophora williamsii (peyote)?
A
Mescaline
7
Q
What drugs are derived from Ayahuasca?
A
DMT, harmine, harmaline
8
Q
What drugs are derived from Anadenanthera peregrine and Virola trees?
A
DMT and bufotenin
9
Q
What drugs are derived from Atropa belladona, Datura, Henbane, and Mandrake?
A
Atropine, scopolamine, hyoscamine
10
Q
What drug is derived from Tabernatnthe iboga roots?
A
Ibogaine
11
Q
What drugs are derived from Myristica fragrans?
A
Myristicin
Elemicin
12
Q
What are the chemical forms of hallucinogens?
A
Indoleamine nucleus
Phenethylamine nucleus
Catechol nucleus
Dissociatives and deliriants
13
Q
Are all hallucinogens safe?
A
No
14
Q
What is foundational to accessing the subconscious and avoiding bad trips for medical use?
A
Set and settings
15
Q
How do we classify psychedelics?
A
Vivid sensations, altered perceptions and reality
User are still responsive, communicative
16
Q
How do we classify deliriants?
A
Vivid, maybe confusing, fantasy
17
Q
How do we classify dissociatives?
A
Analgesia, amnesia, catalepsy, detached reality
18
Q
What are the big 3 effects of hallucinogens?
A
Hallucination = an experience involving the perception of something that may not actually be present
Illusion = altered and distorted perceptions, thoughts, feelings, insights, awareness
Delusion = fixed belief, unchanged by conflicting evidence
19
Q
What are trips dependent on?
A
Mindset and setting
20
Q
What is potency like from high to low in hallucinogens?
A
LSD->Mescaline
21
Q
What do prototypical psychedelic LSD and 5HT21 receptor biology affect?
A
Frontal cortex thought and perception plus locus coeruleus and thalamus
22
Q
How is LSD administered?
A
Ingested, injected, transdermal
23
Q
How much LSD is present in one dose?
A
10-300 mg
24
Q
What tools are used to administer LSD?
A
Blotting paper, sugar cube, gel caps, pressed tablets/microdots
25
What is microdosing?
using sub-psychedelic amounts
26
What is the onset of LSD?
30-90 minutes
27
How much LSD enters the brain?
1%
28
What is the TI of LSD?
>1000
29
How is LSD metabolized?
By the liver
30
What is the half-life of LSD?
110-175 minutes
31
What is the duration of an LSD high?
5-12 hours
32
Where does LSD have a high occupation time?
5HT2a receptors
33
What is stage 1 of an LSD trip?
0-30 minutes
Physiological changes outside the brain, sympathomimetic, dizziness, nausea, muscle tremors, numbness
34
What is stage 2 of an LSD trip?
30-120 minutes
Alteration of perceptions, familiar objects take on new appearances, time is lengthened, intense colours, patterns/textured illusions, movement in stable objects, intense sounds, smells, tastes, synesthesia
35
What is stage 3 of an LSD trip?
3-5 hours
Illusions continue, perception of self as mind/body disconnect, distorted body appearance, deeper sense of self
36
What are the psychological effects of LSD intoxication?
Visual hallucinations and illusions
Synesthesia
Time and physical distortions
Intense emotion
Mystical, spiritual encounters
Introspection, ego dissolution
37
What is synesthesia?
Overlapping senses, altered thalamic routing
38
What are the cognitive effects of LSD intoxication?
Inability to concentrate/focus, preoccupation with trivial thoughts, impaired judgment, communicating with God or telepathy with other animals
39
How is LSD sympathomimetic?
Increases BP
Vasoconstriction
Sweating
Dilated pupils
40
What are animal behaviours on LSD?
Animals will not self-administer
Animals actually evoke effort to stop administrations
41
What does LSD activate?
D2-like signaling in the NAc and striatum
Not rewarding
May drive hallucinations
42
What are the physiological mechanisms of LSD?
LC fear centre, 5HT21 in other regions projects to LC, augments LC responses to regular events into extremely novel, seemingly new encounters
Thalamus - routing hub for sensations, mixing of inputs and outputs
43
What is LSD an agonist of?
An agonist at 5-HT1A/B, 2A/B/C, 6 and 7; primarily 2A
44
What are the cellular mechanisms of LSD action?
High pre-synaptic expression in the cortex = perception and information processing centres
Controls transcriptional programming even after a single use
Presynaptic in mPFC
Governs neuroplastic changes via glutamate signaling
Complementary actions by other 5HT receptors and DA receptors
High affinity agonist at D2-like receptors, coupled to Gi/o
45
What part of the receptor structure explains a high occupation time for LSD?
L229
46
What do drug-receptor interactions allow for?
Selection of signaling capabilities
47
How do receptor conformations bias signaling in LSD?
Gaq -> PKC and Ca2+ pathways are activated by non-hallucinogenic chemicals
Prolonged receptor occupation shifts activation away from Gaq
Hallucinogens activate beta-arrestin = desensitization/internalization, MAPK pathways
48
Do hallucinogens evoke positive reinforcement?
Not typically
LSD is low on abuse scale potential
49
What drug may evoke positive reinforcement?
Deliriants (muscarinics)
-M2/4 are Gi/o linked
-M5 is Gq linked, elevates intracellular Ca2+
50
How is psilocybin absorbed?
Ingested
51
What is the duration of psilocybin?
3-6 hours
52
What are some of the effects of psilocybin?
Milder version of LSD
No flashbacks, no lethal cases
Sympathomimetic, altered time and perceptions, hallucinations, heightened emotions
53
What is psilocybin metabolized to and where?
Metabolized to psilocin in the gut and liver
54
What is psilocybin an agonist of?
5HT2a
55
Is psilocybin addictive?
Not addictive, rapid tolerance
56
How is DMT absorbed?
Snorted, smoked, or injected
57
What happens to DMT in the gut?
It is destroyed in the gut
58
What could DMT be used to treat?
Worms, parasites
59
What is DMT an agonist of?
5-HT2A/C and 1A
60
Do we build a tolerance to DMT?
No
61
What are the physiological effects of DMT?
Similar to LSD and psilocybin
62
What are the psychological effects of DMT?
Intense, vivid hallucinations, emotions, introspection, connection to surroundings
63
What is found in harmine and harmaline?
Beta-carboline chemicals
64
What types of inhibitors are harmine and harmaline?
Selective and reversible monoamine oxidase-A inhibitors
Acetylcholinesterase inhibitors
65
What might an acetylcholinesterase inhibitor be useful in treating?
Alzheimer's disease
66
What can harmine and harmaline treat?
Parkinson's due to stimulating striatal DA release at high doses
67
How is DMT protected in Ayahuasca?
The MAO inhibitors in the beta-carbolines protect DMT from degradation so there is enhanced distribution in the brain
68
What are the effects of Ayahuasca?
Activates vision and memory brain regions
Powerful visions, intense emotion, profound introspection
69
What are the adverse effects of Ayahuasca?
Vomiting, diarrhea
70
What is bufotenin chemically similar to?
5HT
71
What are the common effects of bufotenin?
Drooling, heat palpitations, elevated BP, oxygen depletion, cramped muscles, blurred vision, headache, toad breath
72
What are hallucinations from bufotenin caused by?
Decreased oxygen to the optic nerve
73
What else do toads produce?
Toxic glycosides that cause dysrhythmias
74
How might ibogaine block addiction circuits?
Elevates glial cell line-derived neurotrophic factor in the midbrain
GDNF release in the VTA reduces cravings and drug intake
75
What are the adverse effects of ibogaine?
May damage cerebellum, cause severe motor tremors, increase risk of heart attack and seizure
76
How is mescaline absorbed?
Ingested
77
What is the duration of mescaline?
4-12 hours
78
What is the TI of mescaline?
7-30
79
What are the effects of mescaline?
Vivid hallucinations similar to LSD
80
What are the adverse effects of mescaline?
Toxic effects evoke nausea and vomiting
Death due to convulsions and respiratory arrest
81
How are nutmeg and mace absorbed?
Ingested, inhaled, insufflated
82
What do low doses (5g) of nutmeg and mace cause?
Very mild hallucinations, disorientation, confusion, feelings of unreality, euphoria
83
What do higher doses (5-30g) of nutmeg and mace cause?
Hallucinations, facial flushing, dizziness, apprehension, nausea, vomiting
Unreality can persist for days
84
How do you microdose psychedelics?
Sub-hallucinogenic doses, 1 day on/2 days off for a few weeks
85
What hallucinogens are used to microdose?
Primarily LSD and psilocybin
86
What are the benefits of micro-dosing?
Emerging studies support beneficial effects on mood, creativity, outlook
87
What does 5HT underlie?
Complex cognitive and emotional functions in humans
88
What does 5HT2a expression in sub-cortical nuclei alter?
Functional connectivity = support perception, memory, attention
89
What are some plant-derived anticholinergics?
Mondragora officianrum (mandrake)
Atropa belladonna (nightshade)
Datura stramonium (datura)
Hysocyamus niger (henbane)
90
What are the effects of mandrake at low doses?
Relieve anxiety, induce sleep
91
What are the effects of mandrake at high doses?
Cause hallucinations, amnesia, muscular paralysis
92
What are the 3 primary tropane alkaloids in plant-derived anticholinergics?
Atropine, scopolamine, hyoscyamine
93
What types of doses are required for hallucinations from plant-derived anticholinergics?
High, near toxic doses
94
What do plant-derived anticholinergics block?
Muscarinic AChRs which dilate pupils, increase heart rate, dry secretions
95
What are the physiological effects of anticholinergics?
Elevates heart rate, dry mouth, lack of perspiration, constipation, difficultly urinating
96
Why can anticholinergics be fatal?
They cause rapid heart rate, hyperthermia, asphyxia
97
Do anticholinergics produce euphoria?
No
98
What do anticholinergics prevent?
ACh-mediated activation
99
What are some forms of dissociatives?
Phencyclidine, ketamine anesthetics
Amanita muscaria, Salvia divinorum
100
What are the effects of dissociatives?
Completely removed from reality, detached
101
What do dissociatives produce in animal models?
Reinforcement
Unique hallucinations but not due to augmented DA release in the NAc
102
How is PCP absorbed?
Inhaled, dip a cigarette in free-base and smoke it
Ingested, insufflated, injected
103
What is the duration of PCP?
4-8 hours
104
What is the TI of PCP?
10-15
105
What are the effects of 5mg of PCP?
Anesthetic, analgesic, stimulant, depressant, convulsant, hallucinogen
106
What are the effects of 10mg of PCP?
Any combination of muscle rigidity, loss of pain sensitivity, agitation, mood swings, combative, sympathomimetic, visual/auditory hallucinations, detachment
107
What does PCP block?
NMDARs in the cortex and hippocampus
108
What does PCP increase the synthesis and release of?
DA, causing agitation, stimulation, locomotor activity
109
What effects of PCP may last for days or weeks?
Delirium, confusion, paranoia, impaired memory
110
What is a toxic dose of PCP?
>20mg, can cause convulsions, respiratory failure, coma, death
111
What are most PCP deaths linked to?
Behaviours while tripping
112
How is ketamine absorbed?
Ingested, inhaled, insufflated, injected
113
What is the onset and duration of ketamine?
15-20 minute onset
35-60 minute duration
114
What are the effects of ketamine?
Same effects as PCP but shorter acting
115
What are the cellular mechanisms of PCP and ketamine?
Block the NMDAR ion channel
Affect Glu, NE, DA, ACh, 5-HT neurotransmitters
116
What is dependence on PCP and ketamine like?
Moderate risk, mildly reinforcing but no DA increases in the NAc
PCP self-administration in animal models
Mostly psychological, slight physical dependence
Ketamine dependence is linked to access, not neurocheistry
117
What are the adverse effects of PCP and ketamine?
Psychosis and analgesia which leads to damaging behaviors
-attempting superhuman feats
Ketamine cystitis
Memory loss, speech problems, delusional thinking
118
What is ketamine cystitis?
Arrest bladder cell growth which causes cell death
Causes bloody urine, pain, incontinence
119
How is Amanita muscaria absorbed?
Ingested
120
What is the onset and duration of Amanita muscaria?
30-90 minute onset
Up to 12 hour duration
121
What effects of Amanita muscaria can last for days?
Withdrawal headaches, amnesia, sleepiness
122
What happens to the active chemical in Amanita muscaria?
Is excreted in the urine unchanged
123
What are the effects of Amanita muscaria?
Alter body perception, euphoria, dizziness, vivid hallucinations
Muscle twitches, sweat, salivation, constricted pupils, lowered BP
124
What is muscimol?
The GABAaR agonist responsible for most effects
125
What does ibotenic acid do?
Binds to NMDARs
126
What is the fatal dose of Amanita muscaria?
Around 15 mushroom caps
127
How is Salvia divinorum absorbed?
Inhaled, chewed
128
What is the duration of Salvia divinorum?
15-120 minute duration
129
What are the effects of Salvia divinorum?
Vivid visuals, sensory and time disturbances, detachment and floating through time
Nausea, slurred speech, chills
130
What can a high dose of Salvia divinorum cause?
Brain lesions
131
What is Salvinorin A?
One of the three non-alkaloid hallucinogens
132
What type of agonist is Salvia divinorum?
A potent kappa opioid receptor agonist that causes dysphoric effects, anxiety, fear, and confusion in most cases
133
What are new psychoactive substances?
Chemical alteration of existing drugs
134
What are 2-C drugs?
5HT receptor agonists, likely other receptors/transports too
Produce hallucinations, stimulant effects
135
What are the adverse effects of 2-C drugs?
Seizure, extremity rigidity, lethal
136
What is Bromo-dragonFLY?
Benzodifuran
137
What is the duration of Bromo-dragonFLY?
1-3 days
138
What does Bromo-dragonFLY bind to?
5HT1 and 2A receptors
139
What does Bromo-dragonFLY cause?
Severe vasoconstriction via alpha-adrenergic receptors
Similar effects to LSD
140
Why have there been several Bromo-dragonFLY overdose deaths?
Because it has a narrow therapeutic window
141
What are N-benzyl-oxy-methyl drugs?
Potent 5HT2a agonists
