Ayahuasca as a mind enhancer its knowledge and potential OLGA SILVA E MÁRIO SIMÕES

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1 Ayahuasca as a mind enhancer its knowledge and potential OLGA SILVA E MÁRIO SIMÕES

2 Ayahuasca Herbal preparation made by decoction according to different traditional recipes Psychotria viridis 2 Banisteriopsis caapi leaf Photo by A. Ribeiro and C Silva, Lab. Pharmacognosy, FFULisboa stem Photo by A. Ribeiro and C Silva, Lab. Pharmacognosy, FFULisboa

3 Ayahuasca Herbal hallucinogen originally used by indigenous groups in the Amazon Northwest region for ritual and medicinal purposes and now also used in Europe and North America Preparação de Ayahuasca. In d_chacruna_cocinando.jpg 3 Ayahuasca. In paration.jpg

4 Ayahuasca 4 Main alkaloids Psychotria viridis leaf Banisteriopsis caapi stem N,N-dimethyltryptamine 5-HT2A receptor agonist Harmine* Tetrahydroharmine Harmaline* Harmol* *monoamine-oxidase-inhibitors

5 Ayahuasca Main alkaloids 5 Monoamine-oxidase reversible inhibitors EC50 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-B THH is a poor MAOI but can acting as a 5-HT reuptake inhibitor 5-HT 2A receptor agonist N,N-dimethyltryptamine substrate for the serotonin transporter (SERT) and for the vesicular monoamine transporter DMT dose of mg/kg - affect, intensity, cognition, and volition 0.1 mg/kg iv DMT - perception Less than 0.05 mg/kg - somatesthesia

6 Ayahuasca Since the last century Ayahuasca has aroused the 6 interest of the scientific community Scientific studies Oncology CNS Addition ++ Depression ++ Alzheimer Parkinson

studies - DMT and harmine Anticancer activity Central nervous system

7 Ayahuasca 7 Scientific studies Scientific studies are mainly correlated or made with 2 of the major compounds -cell and animal model pre-clinical studies - DMT and harmine Anticancer activity Central nervous system diseases Depression Neurodegenerative diseases Parkinson Addition - mindfulness changing

8 Ayahuasca Pre-clinical pharmacological studies 8

9 Ayahuasca Clinical studies 9

Ayahuasca Toxicity (1) 10 Only 13 studies were identified in Pubmed Usual Dose taken during a religious ritual 2017, in press 0.146 mg/ml of DMT, 0.12 mg/ml of harmaline, and 1.

10 Ayahuasca Toxicity (1) 10 Only 13 studies were identified in Pubmed Usual Dose taken during a religious ritual 2017, in press mg/ml of DMT, 0.12 mg/ml of harmaline, and 1.56 mg/ml of harmine concerning Ayahuasca AND toxicity Non-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,Ndimethyltryptamine,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 nonmonotonic dose response.

Ayahuasca Toxicity (2) 11 Doses of 30X and 50X the dose taken during a religious ritual 2015, in press Higher neuronal activation in all brain areas involved in serotoninergic neuro-transmission.

11 Ayahuasca Toxicity (2) 11 Doses of 30X and 50X the dose taken during a religious ritual 2015, in press Higher neuronal activation in all brain areas involved in serotoninergic neuro-transmission. Although this led to some brain injury, no permanent brain damage was detected at a 30X ayahuasca dose Neuronal 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 areas Lethal oral dose higher than the 50X (which corresponds to 15.1 mg/kg bw DMT).

12 Ayahuasca 12 Phenomenology I The vision "You see jaguars, or snakes, or people you know. People can "step in" from the scene of vision, "walk through it and / or act and interact with objects and creatures they encounter."

13 Ayahuasca vision 13 Pablo Amaringo Destino (esq.) e Trueno Ayahuasca (dir.) In

14 Ayahuasca 14 Phenomenology II The Ayahuasca s vision Vision of problem solving, "soul flights," and experiences of clairvoyance. Vision linked to the transcendent

15 Ayahuasca 15 Phenomenology II Secondary effects Emetic episodes - called "purges" Changes in body perception Diarrhea Tachycardia Nausea Crying episodes

intervals of 120 minutes Average session duration

16 Ayahuasca Administration and use Fasting of minimal 6h With or without ritual Successive intakes, with intervals of 120 minutes Average session duration 4h to 6h Songs: "Icaros" and / or Christian hymns 16

17 Ayahuasca 17 Transforming inner experiences I Psycho-biographic Traumatic events in the lives of the person are revived. Behaviors and choices that influenced the present situation of life Loizaga-Velder A. (2013) Liester MB, Prickett JI (2012)

18 Ayahuasca 18 Transforming inner experiences II Psycho- biographic Answers to past and future problem issues Significant "encounters" with deceased Loizaga-Velder A. (2013) Liester MB, Prickett JI (2012)

19 Ayahuasca 19 Transforming inner experiences III Emotional (1) Inner pacification and purification Extasis and/ or feeling of integration in a divine purpose Self disclosure and discovery Loizaga-Velder A. (2013) Liester MB, Prickett JI (2012)

20 Ayahuasca 20 Transforming inner experiences IV Emotional (2) Direct confrontation with their own (self) emotions Increased empathy, improved relational capacity Mysterium tremendum et fascinans

21 Ayahuasca Neuro-psychiatric uses Addictions Alcohol and heavy drugs Anxiety Depression PTSD Psychotherapy enhancer Parkinson disease Alzheimer / dementia 21

22 Ayahuasca As a potential medicine? 22 Different raw material and way of herbal recipe preparation Different chemical profile of each preparation Different content in the major detected alkaloids 5-HT receptor agonist monoamine-oxidase-inhibitors Different levels of pharmacological activity and of toxicological profiles No comparative data analysis could be made between samples from different origins no conclusive data can be used to validate the usefulness

Ayahuasca Chemical composition 23 20 samples from an ayahuasca cooking process were used N,N-dimethyltryptamine, tryptamine, harmine,

23 Ayahuasca Chemical composition samples from an ayahuasca cooking process were used N,N-dimethyltryptamine, tryptamine, harmine, harmaline, harmalol, and tetrahydroharmine were quantified Concentrations of the target compounds ranged from 0.3 to 36.7 g/l for the samples

Quality Control Rules In vivo Efficacy (mode of action) tests - Larger samples In vivo Toxicity Evaluation Including

24 Ayahuasca 24 Conclusion More research is need at preclinical and after at clinical level, using: Well characterized raw material, according to International Quality Control Rules Standardized formulations, according to International Quality Control Rules In vivo Efficacy (mode of action) tests - Larger samples In vivo Toxicity Evaluation Including genotoxicity and repeated dose toxicity tests Clinical assays with larger samples and randomized and blinded test designs

25 25 Thank you very much for your attention!!! Olga Silva Universidade de Lisboa, Faculty of Medicine Mário Simões Universidade de Lisboa, Faculty of Medicine

26 26

Neurotransmitters acting on G-protein coupled receptors

Neurotransmitters acting on G-protein coupled receptors Part 2: Serotonin and Histamine BIOGENIC AMINES Monoamines Diamine Indolamines: Serotonin Basic Neurochemistry. FIGURE 15-1: Chemical structure of