Hallucinogens Flashcards by Cambell Meier

Hallucinogens

Generate perceptual and cognitive distortions
* Absence of toxic delirium

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Psychomimetic (psychosis)

No longer considered to accurately reflect psychosis

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Psychedelic

(mind-opening)

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Hallucinogenic

(producing hallucinations)

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Hallucinogens names

Mescaline, LSD, DMT, and psilocybin

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Mescaline

Psychoactive alkyloid found in
peyote cactus

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Mescaline Entheogenic effects

– used in
transcendent rituals

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Psilocybin

Endogenous active alkyloid prodrug
found in mushrooms of the genus
Psilocybe

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Psilocybin is metabolized to

psilocin
(psychoactive metabolite) in the body

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Dimethyltryptamine - DMT

Psychoactive tryptamine found in South
American vines such as Psychotria

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Dimethyltryptamine - DMT Traditionally brewed as a strong tea called

ayahuasca – ‘vine of the soul’

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Dimethyltryptamine - DMT Only psychoactive when brewed with
Banasteriopsis caapi vines – contain

β-carbolines
(reversible MAO inhibitors)

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β-carbolines are proposed to inhibit

t first pass
metabolism of DMT by MAO

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Lysergic acid diethylamide (LSD)

synthetic Lysergic acid is the chemical precursor to ergot
alkyloid

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LSD first marketed in 1947 as

Delysid for neurotic patients – used to uncover repressed thoughts or feelings

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Use of LSD as a

psychotomimetic gave
way to ketamine or PCP as it was
realized LSD does not accurately
recapitulate psychosis

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Psycholytic therapy involved

low dose
LSD to promote release of repressed
memories

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Psychedelic therapy

High dose LSD used to induce druginduced spiritual experience

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Psychedelic therapy (psilocybin) improved

depression scores in patients with treatment-resistant depression

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amygdala hyperactivity and psilocybin

Normalization of amygdala hyperactivity was seen in fMRI followup

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Hallucinogens were reintroduced to the Western world by three influential
figures

Aldous Huxley
Gordon Wasson
Timothy Leary

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Aldous Huxley

Depicted his first experience with mescaline in the 1954 essay The Doors of
Perception

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Gordon Wasson

First known Westerner to participate in a Mazatec mushroom ritual - seeking the magic mushroom

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Timothy Leary

Founded the Harvard Psychedelic Drug Research Program – administered
psilocybin and LSD to numerous grad students and faculty

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Project MKUltra

Goal was to investigate potential methods for mind control and interrogation

MKUltra extensively investigated the effects of

LSD on servicemen and sometimes unwitting members of the public

Most hallucinogens are readily available

e orally

Potency is varied

LSD has an exceedingly high potency

Oral doses typically have a

delayed onset of 30-90 minutes

Greatest impact on onset is

presence of food

Typically long-lasting effects

LSD and mescaline are psychoactive for 6-12 hours Psilocybin somewhat shorter

DMT Recreational use is by

inhalation (smoking)

DMT Rapid onset and effect

t (peak in 5-20 minutes)

DMT Effects subside within

n 1 hour (‘business trip’)

DMT Administered orally in

ayahuasca the presence of MAO inhibitors extend the effects for several hours

Drug effects Onset, Plateau, Peak, Come-down

Onset (30-60 minutes) Plateau (~2 hours) Peak (~2-3 hours) Come-down (~2 hours)

Onset

Visual effects * Intensification of colours – perception of ‘new’ colours * Geometric shapes, particularly with eyes closed

Plateau (~2 hours)

Slowed perception of time * Increasingly intense visual effects

Peak (~2-3 hours)

Pronounced alteration of perception of time Feeling of being in another world Intense visual hallucinations Synesthesia

Come-down (~2 hours)

Decreasing effects typically dissipating within 3 hours

After effects may last

through next day

After effects may last through next day

Lingering increased perceptions and sense of well-being

Hallucinogenic experiences typically fall into one of two categories

good trip bad trip

Good trip

overall mystical or spiritually enlightening experience

Bad trip

– disturbing or frightening experience

Many factors influence perceptions

Dose, expectations, personality, previous drug use, physical and social context

Some suggestion that hallucinogens enhance a subject’s

own state

Disturbing experiences may result from

amplification of negative mood or thoughts

fMRI studies have surprisingly shown that hallucinogens induce

broad significant decreases in activity (blood flow/BOLD)

fMRI studies have surprisingly shown that hallucinogens induce broad significant decreases in activity (blood flow/BOLD) Significant changes occur in hub areas including the

cingulate cortex (ACC/PCC) and prefrontal cortex (mPFC).

fMRI studies have surprisingly shown that hallucinogens induce broad significant decreases in activity (blood flow/BOLD). Significant changes occur in hub areas including the cingulate cortex (ACC/PCC) and prefrontal cortex (mPFC). Decreases in activity correlate with

subjective ratings of intensity.

Overall decreased activity of hubs in the default mode network proposed to produce

effects by supressing ‘self’ or ‘ego’ and enabling unconstrained cognition.

Some activation of the

sympathetic nervous system is seen with hallucinogens

* LSD produces pronounced

pupil dilation – aversion to bright light

LSD produces Small increases in

heart rate, blood pressure, body temperature

Dizziness, nausea, and vomiting are a possible adverse effect of

LSD ingestion

Dizziness, nausea, and vomiting are a possible adverse effect of LSD ingestion Much more common with consumption of

whole peyote or psilocybin-containing mushrooms, very common with ayahuasca

Indoleamine hallucinogens

Psilocin, DMT, and LSD contain indoleamine structures that are analogous to 5-HT.

Phenethylamine hallucinogens

act as central nervous as hallucinogens higher structural homology to catecholamines

Mescaline has higher structural homology to

catecholamines.

Phenethylamine hallucinogens Similar to the neurotransmitter

norepinephrine and the amphetamine-class of psychostimulants.

Amphetamine can produce

e hallucinogenic effects with prolonged use, though analogues such as DOM, TMA more potent/selective hallucinogens.

Hallucinogenic effects are produced through

seratonergic systems

LSD has affinity at 8 5HT receptors

1A, 1B, 1D, 2A, 2C, 5A, 6, 7

Both indoleamine and phenethylamine hallucinogens agonise the

5-HT2A receptor

5-HT2A antagonism

Subjective effects of psilocybin were blocked by pretreatment with either ketanserin (5-HT2A antagonist, antihypertensive) or risperidone (5HT2A inverse agonist and D2 antagonist, atypical antipsychotic)

5-HT2A antagonism D2 antagonism

did not affect subjective effects (haloperidol – D2 antagonist, typical antipsychotic).

Animals can be trained to

discriminate drug effects.

Rats trained to press alternate levers after either LSD or saline injection

reflects the internal stimulus from drug effects.

LSD discrimination can be extinguished by administration of

5-HT2A antagonists

Hallucinogens develop rapid

tolerance

LSD administration over 4 days results in

near complete tolerance

5HT2A receptors are downregulated with

daily dosing of LSD or psilocybin in rats (pharmacodynamic tolerance)

Mescaline does not result in

receptor downregulation

Crosss-tolerance develops to

o LSD & psilocybin suggesting further mechanisms at play

Dependence and abuse are

NOT demonstrated to hallucinogens

Users do not

binge or crave

withdrawal

No withdrawal syndrome develops (‘hangover’ symptoms include enhanced perception of colours and a lingering sense of well-being)

No mechanisms of dependence are described in

humans or animals

Widely considered to have no

abuse potentia

A bad trip can result in

acute anxiety or panic reaction

Early clinical studies suggest bad trips can

be minimized with thorough screening

Hallucinogen persisting perception disorder (HPPD)

Flashbacks’ * Re-experiencing perceptual symptoms associated with intoxication after cessation of drug use * Documented but extremely rare phenomenon (but widely discussed)

At one time psychosis was considered a

significant risk