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
