Entheogenic Tryptamines of Shamanic Origins : Ayahuasca Psilocybin

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 Tetrahydroharmine Harmine

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-HT2A, 5-HT2C, 5-HT5B, 5-HT7) 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 • DrugPart. 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”.