Hallucinogens Flashcards
Describe hallucinogens
- Generate perceptual and cognitive distortions
- Absence of toxic delirium
- Psychedelic (mind-opening)
- More common in recreational & clinical context
- Hallucinogenic (producing hallucinations)
- Preferred pharmacologically
What is mescaline?
- Psychoactive alkyloid found in
peyote cactus
Describe psilocybin metabolism
- Psilocybin is metabolized to psilocin
(psychoactive metabolite) in the body
Describe DMT
- Traditionally brewed as a strong tea called
ayahuasca– ‘vine of the soul’ - β-carbolines are proposed to inhibit first pass
metabolism of DMT by MAO
Describe psychotics and psychedelic therapy
- LSD first marketed in 1947 as Delysid for neurotic patients – used to uncover repressed thoughts or feelings
- Sandoz recommended psychiatrists self-administer Delysid to better understand psychosis experienced by Schizophrenics
Describe psychedelic therapy
- Use of LSD as a psychotomimetic gave
way to ketamine or PCP as it was
realized LSD does not accurately
recapitulate psychosis - Psychedelic therapy
- High dose LSD used to induce drug-
induced spiritual experience
Describe Timothy Leary
Founded the Harvard Psychedelic Drug Research Program – administered
psilocybin and LSD to numerous grad students and faculty
Describe the pharmacology of hallucinogens
- Most hallucinogens are readily available orally
- 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
- DMT is the exception
- Recreational use is by inhalation (smoking)
- Rapid onset and effect (peak in 5-20 minutes)
- Administered orally in ayahuasca the presence of MAO inhibitors extend the effects for several hours
Describe stages of drug effects
- Onset (30-60 minutes)
- Plateau (~2 hours)
- Peak (~2-3 hours)
- Come-down (~2 hours)
- Lingering increased perceptions and sense of well-being
Describe the variety of effects of hallucinogens
- Hallucinogenic experiences typically
fall into one of two categories: - Good trip – overall mystical or
spiritually enlightening experience - Bad trip – disturbing or frightening
experience - Disturbing experiences may result
from amplification of negative mood
or thoughts
Describe neurological changes
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).
Overall decreased activity of hubs
in the default mode network
proposed to produce effects by
supressing ‘self’ or ‘ego’ and
enabling unconstrained cognition.
Describe physiological changes
- LSD produces pronounced pupil dilation – aversion to bright light
- Much more common with consumption of whole peyote or
psilocybin-containing mushrooms, very common with ayahuasca
Describe indoleamine hallucinogens
Psilocin, DMT, and LSD contain
indoleamine structures that are
analogous to 5-HT.
These similarities identified in the early
50’s propelled 5-HT (only described in
the CNS in 1953) to the forefront of
behavioural and psychiatric research.
Describe phenethylamine hallucinogens
Mescaline has higher structural homology to
catecholamines.
Amphetamine can produce hallucinogenic
effects with prolonged use, though analogues
such as dimethoxy-4-methamphetamine (DOM)
and 3,4,5-trimethoxyamphetamine (TMA) are
more potent/selective hallucinogens.
Describe serotonergic receptor interactions
- Hallucinogenic effects are
produced through seratonergic
systems - Most have numerous
interactions - LSD has affinity at 8 5HT
receptors: - 1A, 1B, 1D, 2A, 2C, 5A, 6, 7
- Consensus is effects are
primarily through 5-HT2A - Both indoleamine and
phenethylamine hallucinogens
agonise the 5-HT2A receptor
Describe 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).
D2 antagonism did not affect subjective effects
(haloperidol– D2 antagonist, typical
antipsychotic).
Describe drug discrimination trials
Self-administration of hallucinogens is not
demonstrable in animal models.
Describe tolerance and dependence
- 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) - Dependence and abuse are NOT
demonstrated to hallucinogens - Users do not binge or crave
- 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
potential
Describe adverse effects
- A bad trip can result in acute anxiety or
panic reaction - Generally managed by support (talking
someone through a bad trip) - Hospitalization is rarely required – supportive
measures provided - 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)
