Entheogenic Tryptamines of Shamanic Origins : Ayahuasca Psilocybin Presented By: Stacey King, Derek Lee, and Steven Phillips 01/19/01

History Definition: An Amazonian brew, also called yage, containing powerful hallucinogenic alkaloids used for spiritual purposes. In native Quechuan language “ayahuasca” means “vine of the dead.” Folk Use: --Pre-Columbian rock drawings --Early explorer- Richard Spruce --Medicine of the Amazonian shamans

Preparation Gathering: Prayer and fasting Ingredients/Botany: Banisteriopsis caapi - Vine of the soul Psychotria viridis - Chacruna Diplopterys cabrerana Peganum harmala others Preparation: Pulverize B. Caapi and boil with P. viridis and other admixture plants for hours Synthetic Versions: Pharmahuasca

Banisteriopsis caapi and Psychotria viridis Banisteriopsis caapi

Effects The Purge: Natural vs. synthetic Hallucination: “Elves”, mandala-like designs, life visions Physiological: Statically higher upregulation of serotonin receptors (Callaway et. al., 1994) EEG shows a higher activity in the visual band (Don et. al., 1998)

Monoamine Oxidase Inhibitors Monoamine oxidase: An enzyme that oxidatively deaminates other biogenic amines such as serotonin, tryptamine, and tyramine, rendering them inactive. Inhibitors: Beta- Carbolines Ayahuasca = 158 mg/dose Pharmahuasca = 1.5 mg/kg Harmaline and harmine (dihydroharmine and tetrahydroharmine) found in B. caapi and P. harmala are reversible inhibitors of MAO-A found in the CNS and MAO-B found in the gastrointestinal tract Evidence: clinical trial by McKenna, Towers, and Abbott (1984) Effects:Beta-carbolines from P. harmala alone elicit a sedative, valium-like psychoactivity, in constrast to B. caapi which is more of a mood up-lifter. Minor hallucinogenic properties in high doses –harmala as an abortificant

Beta-Carboline Structures Harmaline Harmine Tetrahydroharmine

Warning: Dangerous Interactions

Hypertensive crisis: Taking food with Tyramine increases levels of Epinephrine resulting in high blood pressure, treated with nifedipine or clonidine Toxic Serotomimetic Reaction: a.k.a. serotonin syndrome Overstimulation of serotonin causing rigidity, shivering, and and confusion, treated with 5-HT2 blockers Foods to Avoid!!!!! Cheese Alcoholic beverages Ginseng Aged Meat (sausage, bologna, salami) Soy sauce Chocolate and Coffee (lg. amts.)

Hallucinogenic Compounds

DMT (dimethyltryptamine) Taxa containing DMT: Psychotria viridis, Diplopterys cabrerana, Mimosa hostilis, Homo sapiens, several others Peripheral effects include: increased blood pressure, heart rate, core body temperature, endorphins, prolactin, and pupil dilation Hallucinogenic effects of ayahuasca due to DMT

Routes of administration: in order of potency (strong effects) IV injection mg/kg inhalation mg/kg IM injection mg/kg oral inactive unless in presence of MAO inhibitor.38 mg/kg threshold to.8 mg/kg for strong Duration (results will vary) DMT + harmine: min incubation build within 30 min of incubation plateau min 1 hour of diminishing effects inhalation: instant peak effects lasting 5-10 min residual effects min

What? Humans the new source of DMT!? Small amounts of DMT are found in human spinal fluid, blood, and urine. Methyl transferases catalyse synthesis of tryptamines are found in the human lung, brain, cerbrospinal fluid, liver and heart. Transmethylation Hypothesis: –Schizophrenics produce a higher concentration of methylated indolealkyalamines (eg. DMT)

Proposed Mechanism of Action DMT acts on serotonin receptors (5-HT 2A, 5-HT 2C, 5-HT 5B, 5-HT 7 ) which are G- protein coupled and contain a 7 transmembrane domain structure The function of these receptors include: stimulating phospolipase C, increasing phosphoinositide hydrolysis, and increasing cAMP

Serotonin and Psilocin

Proposed Biosynthesis of DMT

Teonanacatl: The Mushroom Flesh of the Gods (Psilocybin and Psilocin) Psilocybe cubensis

History –Archaeological evidence from 1000 B.C.E. –Spanish conquistadors –Gordon Wasson –Alkaloid determination –Timothy Leary, inmates, CIA, and hippies

Psychopharmacology –Threshold dose = 5 mg –Typical dose = mg –30 times more potent than mescaline –.01 times as potent as LSD –Subjective comparison to LSD vs. Leary’s hypothesis: less abstract, not a stimulant –Duration: 4-6 hours –Oral Activity –Potentiated by MAOI but not required

Have you licked a toad today? Bufo alvarius

Bufotenine: Does it really work? Structurally similar to known psychoactive tryptamines Binds at same serotonin receptors as known psychoactive tryptamines Other “goodies” in the toad Can it reach the brain? Partition Coefficients Drug Part. Coef. 5-MeO-DMT 3.30 Psilocin 3.30 Bufotenine 0.06 The epinephrine factor (Chen & Kovarikova, 1967.) B. alvarius vs. B. marinus

References Baskys, A Remington, G (1996): “Brain Mechanisms and Psychotropic Drugs”. Callaway, J et. al. (1994): “Platelet Serotonin Uptake Sites Increased in Drinkers of Ayahuasca”. Psychopharmacology 116: (3) Chin and Kovarikova (1967): “Pharmacology and Toxicology of Toad Venom”. Journal of Pharmaceutical Science 56: Don N et. al. (1998): “Effects of Ayahuasca on the Human EEG”. Phytomedicine 5: (2) McBride, M (2000): “Bufotenine: Toward an Understanding of Possible Psychoactive Mechanisms”. Journal of Psychoactive Drugs 32: (3) Ott, J (1999): “Pharmahuasca: Human Pharmacology of Oral DMT Plus Harmine”. Journal of Psychoactive Drugs 31: (2) Perrine, D (1996): “The Chemistry of Mind-Altering Drugs”.