Olga Silva Professor of Pharmacognosy Faculty of Pharmacy Uversidade de Lisboa STRUCTURED SESSION 38 Ayahuasca Psychotria viridis leaf Banisteriopsis ID: 1034917
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1. Pharmacology of AyahuascaOlga Silva Professor of Pharmacognosy, Faculty of Pharmacy, Uversidade de Lisboa STRUCTURED SESSION 38
2. Ayahuasca Psychotria viridis leafBanisteriopsis caapiPhoto by J. Fericgla in: Domínguez-Clavé E, Brain Research Bulletin, 2016, 126, Part 1,89-101Photo by J. Callaway in: Domínguez-Clavé E, Brain Research Bulletin, 2016, 126, Part 1,89-101stem Photo by A. Ribeiro and C Silva, Lab. Pharmacognosy, FFULisboaPhoto by A. Ribeiro and C Silva, Lab. Pharmacognosy, FFULisboaHerbal preparation made by decoction according different traditional recipes2
3. Ayahuasca Psychotria viridis leaf Banisteriopsis caapi stemMain alkaloidsN,N-dimethyltryptamineHarmine* TetrahydroharmineHarmaline*Harmol*5-HT2A receptor agonist*monoamine-oxidase-inhibitors3
4. AyahuascaMain alkaloidsN,N-dimethyltryptamine5-HT2A receptor agonistMonoamine-oxidase reversible inhibitors4EC50 for the inhibition of MAO-A 8x10-8 M for harmine, 6x10-8 for harmaline 1.4x10-5 M for THH[ ] higher concentrations both harmine and harmaline begin to inhibit MAO-BDMT dose of 0.1–0.2 mg/kg - affect, intensity, cognition, and volition0.1 mg/kg iv DMT - perception Less than 0.05 mg/kg - somatesthesiaTHH is a poor MAOI but can acting as a 5-HT reuptake inhibitorsubstrate for the serotonin transporter (SERT) and for the vesicular monoamine transporter
5. Ayahuasca5Since the last century Ayahuasca has aroused the interest of the scientific community,Scientific studies are mainly correlated or made with 2 of the major compounds - DMT and harmine Anticancer activityCentral nervous system diseases Depression Neurodegenerative diseases – ParkinsonAddition - mindfulness changingScientific studies
6. Ayahuasca6animal modelPharmacological studies
7. Ayahuasca7Clinical studies
8. Ayahuasca80.146 mg/ml of DMT, 0.12 mg/ml of harmaline, and 1.56 mg/ml of harmine Usual Dose taken during a religious ritualNo-observed-adverse-effect-level for chronic and reproductive effects of ayahuasca in male Wistar rats at 2× the ritualistic dose, which corresponds in this study to 0.62 mg/kg bw N,N-dimethyltryptamine,6.6 mg/kg bw harmine and 0.52 mg/kg bw harmaline. A potential toxic effect of ayahuasca in male rats was observed at the 4× dose, with a non-monotonic dose–response.2017, in pressOnly 12 studies were identified in Pubmed concerning Ayahuasca AND toxicityDoses of 30X and 50X the dose taken during a religious ritualHigher neuronal activation in all brain areas involved in serotoninergic neurotransmission. Although this led to some brain injury, no permanent brain damage was detected at a 30X ayahuasca doseNeuronal activation (c-fos marked neurons) and toxicity (Fluoro-Jade B and Nissl/Cresyl staining) were investigated in the dorsal raphe nuclei (DRN), amygdaloid nucleus, and hippocampal formation brain areasLethal oral dose higher than the 50X (which corresponds to 15.1 mg/kg bw DMT).2015, in pressToxicity
9. AyahuascaDifferent raw material and way of herbal recipe preparation5-HT receptor agonistmonoamine-oxidase-inhibitorsDifferent content in the major detected alkaloidsDifferent chemical profile of each preparationDifferent levels of pharmacological activity and of toxicicological profilesNo comparative data analysis could be made between samples from different origins – no conclusive data can be used to validate the usefulness9As medicine?
10. AyahuascaChemical composition1020 samples from an ayahuasca cooking process were usedN,N-dimethyltryptamine, tryptamine, harmine, harmaline, harmalol, and tetrahydroharmine were quantifiedConcentrations of the target compounds ranged from 0.3 to 36.7 g/L for the samples
11. Ayahuasca11ConclusionMore research is need at preclinical and after at clinical level, using:Well characterized raw material, according to International Quality Control RulesStandardized formulations, according to International Quality Control RulesIn vivo efficacy tests - Larger samplesIn vivo Toxicity Evaluation – Including genotoxicity and repeated dose toxicity tests Clinical assays with larger samples and randomized and blinded test designs
12. 12Thank you very much for your attention!!!Olga Silva Department of Pharmacological SciencesFaculty of Pharmacy, Universidade de LisboaAvenida Professor Gama Pinto1649-003 LisboaEmail: osilva@campus.ul.pt