Hallucinogens Flashcards

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1
Q

Describe hallucinogens

A
  • Generate perceptual and cognitive distortions
  • Absence of toxic delirium
  • Psychedelic (mind-opening)
  • More common in recreational & clinical context
  • Hallucinogenic (producing hallucinations)
  • Preferred pharmacologically
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2
Q

What is mescaline?

A
  • Psychoactive alkyloid found in
    peyote cactus
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3
Q

Describe psilocybin metabolism

A
  • Psilocybin is metabolized to psilocin
    (psychoactive metabolite) in the body
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4
Q

Describe DMT

A
  • 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
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5
Q

Describe psychotics and psychedelic therapy

A
  • 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
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6
Q

Describe psychedelic therapy

A
  • 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
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7
Q

Describe Timothy Leary

A

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

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8
Q

Describe the pharmacology of hallucinogens

A
  • 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
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9
Q

Describe stages of drug effects

A
  1. Onset (30-60 minutes)
  2. Plateau (~2 hours)
  3. Peak (~2-3 hours)
  4. Come-down (~2 hours)
  • Lingering increased perceptions and sense of well-being
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10
Q

Describe the variety of effects of hallucinogens

A
  • 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
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11
Q

Describe neurological changes

A

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.

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12
Q

Describe physiological changes

A
  • 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
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13
Q

Describe indoleamine hallucinogens

A

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.

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14
Q

Describe phenethylamine hallucinogens

A

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.

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15
Q

Describe serotonergic receptor interactions

A
  • 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
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16
Q

Describe 5-HT2A antagonism

A

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).

17
Q

Describe drug discrimination trials

A

Self-administration of hallucinogens is not
demonstrable in animal models.

18
Q

Describe tolerance and dependence

A
  • 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
19
Q

Describe adverse effects

A
  • 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)