Topic 28: Hallucinogens Flashcards
What are hallucinogens?
broad category of drugs having convergent effects: generate perceptual and cognitive distortions, absence of toxic delirium
various terminology used: psychomimetic, psychedelic, hallucinogenic
mescaline, LSD, DMT, and psilocybin
What is mescaline?
psychoactive alkyloid found in peyote cactus
peyote endemic to southern Texas and Mexico
long history of peyote use in indigenous culture
entheogenic effects: used in transcendent rituals
peyote buttons found at archeological sites dated to ~3800 BCE
What is psilocybin?
endogenous active alkyloid prodrug found in mushroom of the genus Psilocybe
extensive history of use worldwide
continues use in Central American cultures
cave drawings depicting ritual mushroom use in Algeria have been dated to 3700 - 8000 BCE
psilocybin is metabolized to psilocin (psychoactive metabolite) in the body
What is dimethyltryptamine (DMT)?
psychoactive tryptamine found in South American vines such as Psychotria
traditionally brewed as a strong tea called ayahuasca (“vine of the soul”)
only psychoactive when brewed with Banasteriopsis caapi vines - contain beta-carbolines (reversible MAO inhibitors)
beta-carblines are proposed to inhibit first pass metabolism of DMT by MAO
purified or synthetic DMT is smoked as a street drug: bypasses first-pass metabolism
What is lysergic acid diethylamide (LSD)?
famously synthesized in 1938 by Albert Hofmann at Sandoz labs: discovered the psychoactive effects accidentally in 1943
lysergic acid is the chemical precursor to ergot alkyloids
potent toxin found in parasitic fungus that infests rye and wheat crops, ergotism may have caused 40,000 deaths in 944 CE
ergot alkyloids have medical use as they induce powerful uterine contraction: past use to induce labor and reduce post-birth hemorrhage
How was LSD used in psycholytic 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
use of LSD as a psychotomimetic gave way to ketamine or PCP as it was realized LSD does not accurately recapitulate psychosis
What is psycholytic therapy?
involved low dose LSD to promote release of repressed memories
What is psychedelic therapy?
became increasingly popular through the 50s and 60s
high dose LSD used to induce drug-induced spiritual experience
patients hoped to gain insight into sources of problems
studied from 50s to 70s for treatment of alcoholism: fraught with inconsistent result and poor experimental designs
current resurgence for end-of-life trauma, PTSD, addictions, and treatment resistant depression
self-reported spiritual experiences correlate with increased treatment efficacy
How is psilocybin used for psychedelic therapy?
psychedelic therapy (psilocybin) improved depression scores in patients with treatment-resistant depression
effects were sustained for 6 months in followup study
normalization of amygdala hyperactivity was seen in fMRI followup
Who was Aldous Huxley?
author, grandson of influential biologist Thomas Henry Huxley
depicted his first experience with mescaline in the 1954 essay The Doors of Perception
Who was Gordon Wasson?
investment banker, amateur mycologist
first known Westerner to participate in a Mazatec mushroom ritual
published his account in 1957 Life article “Seeking the Music Mushroom”
Who was Timothy Leary?
clinical psychologist - Harvard lecturer
first experienced mushrooms pm 1959 vacation to Mexico
founded the Harvard Psychedelic Drug Research Program - administered psilocybin and LSD to numerous grad students and faculty
dismissed from Harvard in 1963, continued his work privately
What was Project MKUltra?
Sidney Gottlieb headed MKUltra for the CIA: series of illegal and clandestine human experiments 1953-1973, 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
also involved several plans to drug or assassinate world leaders: several schemes developed to drug Fidel Castro with high doses of LSD
What is the pharmacology of hallucinogens?
most hallucinogens are readily available orally
potency is varied: LSD has 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 is the exception
What is the pharmacology of DMT?
recreational use is by inhalation (smoking)
rapid onset and effect (peak in 5-20 minutes)
effects subside within 1 hour (“business trip”)
administered orally in ayahuasca the presence of MAO inhibitors extend the effects for several hours
What is the onset phase of a hallucinogenic trip?
30-60 minutes
visual effects
intensification of colors, perception of “new” colors
geometric shapes, particularly with eyes closed
What is the plateau phase of a hallucinogenic trip?
~2 hours
slowed perception of time
increasingly intense visual effects
What is the peak phase of a hallucinogenic trip?
~2-3 hours
pronounced alteration of perception of time: suspended time
feeling of being in another world
intense visual hallucinations: bizarre, distorted images (beautiful or menacing)
synesthesia: crossed sensations (hearing colors, tasting music)
What is the come-down phase of a hallucinogenic trip?
decreasing effects typically dissipating within 3 hours
after effects may last through next day
lingering increased perceptions and sense of well-being
What are the variety of effects perceived on a hallucinogenic trip?
hallucinogenic experiences typically fall into one of two categories
good trip: overall mystical or spiritually enlightening experience
bad trip: disturbing or frightening
What are the factors that influence the perceptions of hallucinogenic trips?
dose, expectations, personality, previous drug use, physical and social context
impossible to predict drug effects, many users will experience both good and bad trips
some suggestion that hallucinogens enhance a subject’s own state
disturbing experiences may result from amplification of negative mood or thoughts
What are the neurological changes associated with hallucinogenic use?
fMRI studies have surprisingly shown that hallucinogens induce broad significant decreases in activity (blood flow)
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 suppressing “self” or “ego” and enabling unconstrained cognition
What are the physiological effects of hallucinogens?
some activation of the sympathetic nervous system is seen with hallucinogens: LSD produces pronounced pupil dilation (aversion to bright light), small increases in heart rate, blood pressure, body temperature
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 ayahausca
What are indoleamine hallucinogens?
psilocin, DMT, and LSD contain indoleamine structures that are analogous to 5-HT
these similarities identified in the early 50s propelled 5-HT to the forefront of behavioral and psychiatric research
