Lecture #16, 3/18/96

Lysergic acid amide

• Similar to LSD but only 1/100th as potent
• found in morning glory seeds

Psilocybin

• Flowers grown all over the world
• solacoles(sp?) mushrooms
• In psychedelic mushrooms, the active ingredient is psilocybin
• Teonanacaty - "flesh of gods" in the Aztec language
• Psylocybin --> Psilocin (conversion in animals where a phosphate is lost
• found in numerous species of mushroom which grow throughout the world
• many are of the genus Psilocybe
• chemically identified by Albert Hofmann in the late 1950s
• psilocybin is rapidly metabolized to psilocin
• psychedelic psychoactivity:
  • about 1/300th the potency of LSD
  • typically dose: 10-50 mg
  • typically ingested as dried mushroom
  • dry weight in mushrooms is about 1%
  • making typical dose: 1 to 5 grams of mushrooms
• approximate duration: 5+ hours
• efficient oral and digestive system absorption
• Why is psilocin spared? because, the the hydroxy group in bufotenine prevents going to brain.
• Psilocin has an amine group -> broken down by MAO
• Psilocin also has an OH group -> block to cross blood-brain-barrier
• However, due to internal bonding:
• neutralizes the polar-OH group
• protects amine group from oxidation by MAO
• crosses the blood-brain-barrier and not rapidly degraded by MAO

DMT

• found in dozens of species of South-American jungle plants
• MAO (monoamine oxidase) in digestive system, inactivates DMT --> not psychoactive
• so not active orally, but active in other routes
• Can be inhaled through the nose
• group ritual thing - using blowpipes
• also in beverage called Ayahuasca
• "vine of the soul"
• name applies both to the vine, Bansteriopsis caapi, and most significantly to a beverage having this plant as one of its major components
• the beverage is also known as yage, vegetal, housea, the tea
• widely used by indigenous peoples of the Amazon Basin in South America
• consumed orally as a beverage in ritual ceremonies
• active ingredients in Bansteriopsis caapi, are harmala alkaloids, primarily harmine and harmaline
• minimal psychoactivity at the doses obtained from ayahausca
• Mix harmine/harmaline (MAO inhibitor) with DMT ---> Psychoactive
• "Phase I clinical trials" of ayahuasca in native users in Brazil
• Charles Grob, MD(UCLA) and colleagues
• Reduced alcohol use



Ibogaine

• psychoactive ingredient in the root of Tabernanthe iboga, African shrub
• used ceremonially by several African tribes
• one of the few Old World "psychedelics"
• now at U. of Miami, clinical trials (Stage I) (very low doses) to see if it can help cure heroin addiction
• potentially toxic at high doses (can cause seizures)



Neurochemistry of Classical Psychedelics

• raphe neurons have 5HT(1A) autoreceptors which inhibit firing
• LSD and other tryptamine psychedelics inhibit firing of serotonergic neurons of the raphe
• tryptamine psychedelics are 5HT(1A) agonists
• mescaline and other phenethylamine psychedelics do not have this interaction with 5HT(1A) receptors and this effect on raphe activity
• thus, the 5HT(1A) agonist effect is not key to understanidn the effects of the classical psychedelics
• Note: 5HT(2) receptor are post-synaptic



Phenethylamine psychedelics

Prototypical -> mescaline (3,4,5 trimethoxyphenethylamine)

• first chemically identified psychedelic
• isolated in 1890s
• Natural sources:
  • peyote cactus
  • range from South Texas to North-Central Mexico
  • Lophophora Williamsii
  • Schedule I plant
  • San Pedro cactus
  • Trichocereus pachanoi
  • South America: Ecuador, Peru, Bolivia
  • can grow up to 15 feet high
  • very low concentration (need to make tea out of it by using underneath the leaves)
• psychedelic psychoactivity
• typical dose: 300-500 mg of the sulphate salt, less of chloride salt
• 6 to 12 peyote "buttons"
• about 1/5000th potency of LSD
• approximate duration 6+ hours
• efficient oral and digestive system absorption
• peyote use - in Native American around 1960s from Mexicans as a way to look for something to pull all the Native American together (from U.S. repression)
• Lead to formation of Native American chruch in the early 1900s
• Peyote Law
• peyote classified as Schedule I substance in Federal Controlled Substance Act
• the nondrug use of peyote in religious ceremonies of the Native American Church exempted peyote use in Native American religious ceremonies
• some states (28) have also explicitly exempted peyote use in Native American religious ceremonies
• however, some states(22) have not made usch a explicit exemption
• much lower alcohol use for people in Native American Church than the general Native American population
• Employment Division, State of Oregon vs. Al Smith
• 1984: Native American Al Smith fired from his job as a drug counselor because he admitted to using peyote during a Native American Church religious ceremony
• subsequently denied unemployment benefits
• appealed to Oregon courts and Oregon Supreme Court ruled in Smith's favor
• Oregon attorney general appealed to U.S. Supreme Court
• 1990: Supreme Court decision (Employment Division vs. Smith) ruled that it is up to the state to decide whether or not it wants to grant exemption from prosecution to Native Americans in the use of peyote.
• Religious Freedom Restoration Act
• approved Nov. 1993
• restores "compelling interest test" for laws which impact religious practice
• overruling the first amendment free exercise of religion can only occur if religious practice has been demonstrated to pose serious threat to American government
• Ruled over 1990 decision
• American Indian Religious Freedom Amendment of 1994
• "The use, possession or transportation of peyote by an Indian for bona fide traditional religious purposes in connection with practice of traditional Indian religion is lawful and shall not be prohibited by U.S. or any state"
• explicitly grants Native Americans legal protection at both federal and state level for use of peyote in religious ceremonial occasions
• approved October 1994

Created by Raymond Yakura.