Hallucinogens Flashcards
Hallucinogens
Generate perceptual and cognitive distortions
* Absence of toxic delirium
Psychomimetic (psychosis)
No longer considered to accurately reflect psychosis
Psychedelic
(mind-opening)
Hallucinogenic
(producing hallucinations)
Hallucinogens names
Mescaline, LSD, DMT, and psilocybin
Mescaline
Psychoactive alkyloid found in
peyote cactus
Mescaline Entheogenic effects
– used in
transcendent rituals
Psilocybin
Endogenous active alkyloid prodrug
found in mushrooms of the genus
Psilocybe
Psilocybin is metabolized to
psilocin
(psychoactive metabolite) in the body
Dimethyltryptamine - DMT
Psychoactive tryptamine found in South
American vines such as Psychotria
Dimethyltryptamine - DMT Traditionally brewed as a strong tea called
ayahuasca – ‘vine of the soul’
Dimethyltryptamine - DMT Only psychoactive when brewed with
Banasteriopsis caapi vines – contain
β-carbolines
(reversible MAO inhibitors)
β-carbolines are proposed to inhibit
t first pass
metabolism of DMT by MAO
Lysergic acid diethylamide (LSD)
synthetic Lysergic acid is the chemical precursor to ergot
alkyloid
LSD first marketed in 1947 as
Delysid for neurotic patients – used to uncover repressed thoughts or feelings
Use of LSD as a
psychotomimetic gave
way to ketamine or PCP as it was
realized LSD does not accurately
recapitulate psychosis
Psycholytic therapy involved
low dose
LSD to promote release of repressed
memories
Psychedelic therapy
High dose LSD used to induce druginduced spiritual experience
Psychedelic therapy (psilocybin) improved
depression scores in patients with treatment-resistant depression
amygdala hyperactivity and psilocybin
Normalization of amygdala hyperactivity was seen in fMRI followup
Hallucinogens were reintroduced to the Western world by three influential
figures
Aldous Huxley
Gordon Wasson
Timothy Leary
Aldous Huxley
Depicted his first experience with mescaline in the 1954 essay The Doors of
Perception
Gordon Wasson
First known Westerner to participate in a Mazatec mushroom ritual - seeking the magic mushroom
Timothy Leary
Founded the Harvard Psychedelic Drug Research Program – administered
psilocybin and LSD to numerous grad students and faculty
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
