Ayahuasca as a mind enhancer – its knowledge and potential

OLGA SILVA E MÁRIO SIMÕES

Ayahuasca

Psychotria viridis leaf

Banisteriopsis caapi stem

Photo by A. Ribeiro and C Silva, Lab. Pharmacognosy,

FFULisboa

Photo by A. Ribeiro and C Silva, Lab.

Pharmacognosy, FFULisboa

Herbal preparation made by decoction according to different traditional recipes

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Preparação de Ayahuasca. In https://en.wikipedia.org/wiki/Ayahuasca#/media/File:Ayahuasca_an

d_chacruna_cocinando.jpg

Ayahuasca. In https://en.wikipedia.org/wiki/Ayahuasca#/media/File:Ayahuasca_pre

paration.JPG

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

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Ayahuasca

Psychotria viridis leaf Banisteriopsis caapi stem

Main alkaloids

N,N-dimethyltryptamine

Harmine* Tetrahydroharmine

Harmaline*Harmol*

5-HT2A receptor agonist

*monoamine-oxidase-inhibitors

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Ayahuasca Main alkaloids

N,N-dimethyltryptamine

5-HT2A receptor agonist

Monoamine-oxidase reversible inhibitors

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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

DMT dose of 0.1–0.2 mg/kg - affect, intensity, cognition, and volition

0.1 mg/kg iv DMT - perception

Less than 0.05 mg/kg - somatesthesia

THH is a poor MAOI but can acting as a 5-HT reuptake inhibitor

substrate for the serotonin transporter (SERT) and for the vesicular monoamine transporter

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Scientific studies• Oncology• CNS

• Addition ++• Depression ++• Alzheimer• Parkinson

Since the last century Ayahuasca has aroused the

interest of the scientific community

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- DMT and harmine• Anticancer activity

• Central nervous system diseases

Depression

Neurodegenerative diseases – Parkinson

Addition - mindfulness changing

Scientific studies

Scientific studies are mainly correlated or made with 2 of the major compounds-cell and animal model pre-clinical studies

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Ayahuasca 8Pre-clinical

pharmacological studies

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Ayahuasca 9Clinical studiesO

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0.146 mg/ml of DMT, 0.12 mg/ml of harmaline, and 1.56 mg/ml of harmine

• 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,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 press

Only 13 studies were identified in Pubmed

concerning Ayahuasca AND toxicity

Toxicity (1)

Usual Dose taken during a religious ritual

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• 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).

2015, in press

Toxicity (2)

Doses of 30X and 50X the dosetaken during a religious ritual

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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."

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Ayahuasca – vision

Pablo Amaringo – Destino (esq.) e Trueno Ayahuasca (dir.) In http://ayahuascaceremonies.org/gallery3/index.php/Pablo-C-Amaringo?page=3

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The Ayahuasca’s vision

Vision of problem solving, "soul

flights," and experiences of

clairvoyance.

Vision linked to the transcendent

Phenomenology II

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Secondary effects Emetic episodes - called

"purges" Changes in body perception Diarrhea Tachycardia Nausea Crying episodes

Phenomenology II

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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

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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)

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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)

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Transforming inner experiences III

Emotional (1)

Inner pacification and

purification

Extasis and/ or feeling of

integration in a divine purpose

Self disclosure and discoveryLoizaga-Velder A. (2013) Liester MB, Prickett JI (2012)

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Transforming inner experiences IV

Emotional (2) Direct confrontation with their

own (self) emotions Increased empathy, improved

relational capacity Mysterium tremendum et

fascinans

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Neuro-psychiatric uses

Addictions Alcohol and “heavy drugs”

Anxiety Depression PTSD Psychotherapy enhancer Parkinson disease Alzheimer / dementia

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AyahuascaDifferent raw material and way of herbal recipe preparation

5-HT receptor agonist monoamine-oxidase-inhibitors

Different content in the major detected alkaloids

Different chemical profile of each preparation

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

22As a potential medicine?

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Ayahuasca Chemical composition 23

• 20 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

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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

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Thank you very much for your

attention!!!Olga SilvaEmail: osilva@campus.ul.pt

Universidade de Lisboa, Faculty of Medicine

Mário SimõesEmail: noonauta@gmail.com

Universidade de Lisboa, Faculty of Medicine

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