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

2. 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

3. 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 12- 15 hours Synthetic Versions: Pharmahuasca

4. Banisteriopsis caapi and Psychotria viridis Banisteriopsis caapi

5. 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)

6. 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

7. Beta-Carboline Structures Harmaline Harmine Tetrahydroharmine

8. Warning: Dangerous Interactions

9. 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.)

10. Hallucinogenic Compounds

11. 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

12. Routes of administration: in order of potency (strong effects) IV injection----.4 mg/kg inhalation------.7 mg/kg IM injection---- 1 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: 45-60 min incubation build within 30 min of incubation plateau 45-60 min 1 hour of diminishing effects inhalation: instant peak effects lasting 5-10 min residual effects 30-60 min

13. 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)

14. 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

16. Serotonin and Psilocin

17. Proposed Biosynthesis of DMT

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

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

20. Psychopharmacology –Threshold dose = 5 mg –Typical dose = 10-20 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

21. Have you licked a toad today? Bufo alvarius

22. 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

23. 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) 385-387 Chin and Kovarikova (1967): “Pharmacology and Toxicology of Toad Venom”. Journal of Pharmaceutical Science 56:1535-41 Don N et. al. (1998): “Effects of Ayahuasca on the Human EEG”. Phytomedicine 5: (2) 87-96 McBride, M (2000): “Bufotenine: Toward an Understanding of Possible Psychoactive Mechanisms”. Journal of Psychoactive Drugs 32: (3) 321-331 Ott, J (1999): “Pharmahuasca: Human Pharmacology of Oral DMT Plus Harmine”. Journal of Psychoactive Drugs 31: (2) 171-177 Perrine, D (1996): “The Chemistry of Mind-Altering Drugs”.