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Ayahuasca, Segurança e Pesquisa Biomédica

Apresentado no II Simpósio Internacional sobre o Uso de Plantas Medicinais em Psiquiatria
by

Luís Fernando Tófoli

on 10 August 2016

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Transcript of Ayahuasca, Segurança e Pesquisa Biomédica

Ayahuasca, Segurança e Pesquisa Biomédica
Luís Fernando Tófoli
Universidade Estadual de Campinas - UNICAMP
Very brief introduction to the basics of ayahuasca psychopharmacology

Impact of ayahuasca on health

How important are the biomedical data for the regulation of ayahuasca use?

Moving forward
Agenda
Psychotria viridis
Beta-carbolines
Pesquisa Biomédica na UDV
Projeto Hoasca (1993)
Farmacocinética
Tolerabilidade
Efeitos na Saúde Física e Mental
(Callaway et al. 1994; Grob et al. 1996; Callaway et al. 1999; Callaway, 2005 )
N,N-Dimethyltryptamine (DMT)
DMT
Available in many plants and mammal brains, including humans
(Strassman, 2001)

Biological actions
5HT-2a agonist
High affinity with TAAR-1 (trace-amine associated receptor 1)
Endogenous ligant of sigma-1 receptor
(Brierley e Davidson, 2012)
Monoamine oxidase - MAO
Beta-carbolines
Alcaloids found in plant species:

B. caapi (malpighiaceae)
Passiflora sp. (passifloraceae)
Peganum harmala (nitrariaceae)
Guiera senegalensis (combretaceae)
Beta-carbolines
Biological actions (harmine)

High affinity: MAO-A and DYRK1A (dual specificity tyrosine phosphorylated and regulated kinase 1A) site;

Moderate: 5HT-2A and imidazolines receptors;

Modest: 5HT-2C and dopamine transporter (DAT);

(Brierley e Davidson, 2012)
Pesquisa Biomédica na UDV
Projeto Adolescentes (2002)
Avaliação neuropsicológica
Atitudes
Uso de substâncias
(Doering-Silveira et al. 2005a, 2005b; Silveira et al. 2005; Dobkin de Rios et al. 2005)
Ayahuasca and its pharmacology
Saúde Mental: Efeitos Positivos
Ação protetiva do uso da ayahuasca (em especial o religioso) contra o uso problemático de substâncias
(Doering-Silveira et al. 2005a; Grob et al. 1996; Santos et al. 2006)
Saúde Mental: Efeitos Positivos
Ao primeiro uso:
Avaliação subjetiva positiva, redução de sintomas psiquiátricos menores, aumento dos sentimentos de assertividade, serenidade e vivacidade
(Barbosa et al. 2005)
Saúde Mental: Efeitos Positivos
Adolescentes da UDV: Atitudes altruístas, otimistas e relatos de obediência aos pais e às normas sociais
(de Rios et al. 2005)
Saúde Mental: Efeitos Positivos
Evidência de efeito antidepressivo em modelos animais
(Lima et al. 2006; 2007)
Alívio de sintomas de ansiedade
(Santos et al., 2007)
Saúde Mental: Efeitos Positivos
UDV: Associação positiva com medidas de Saúde Mental
(Grob et al. 1996; de Rios et al. 2005)
Segurança para a Saúde Mental
As evidências levantadas pelo Demec apontam para o uso seguro da Ayahuasca, desde que seguidos os termos da resolução 1/2010 do CONAD
(Lima e Tófoli, 2011)
Acute Subjective Effects
Increase in insight and auto-analysis

A review of past acts judged as morally objectionable

Mystical experiences
Mental health: Positive effects
Protective effect of ayahuasca against drug misuse
(Doering-Silveira et al. 2005a;
Fábregas, 2010; Grob et al. 1996;
Santos et al. 2006; Liester & Prickett, 2012; Bogenschutz & Pommy, 2012; Thomas et al., 2013)
Physical effects
Nausea, vomiting, diarrhea

Mild increase in cardiac frequency and blood pressure

Autonomic effects

(Callaway et al., 1999; Riba et al., 2003)
Health risks
Generally speaking, literature points to general safety

(Frecska, 2011; Grob et al., 1996;
Gable, 2007; Halpern, 2008)
Mental healt: Positive effects
First-use:

Positive subjective evaluation, reduction of minor psychiatric symptoms, increase of feelings of assertivity and vivacity

(Barbosa et al. 2005)
Mental Health: Brazil’s rules
Those interested in drinking ayahuasca for the first time:

Individual interviews.

Ask for past history of severe mental disorder, use of medications and drugs.
Acute Subjective Effects
Changes in perception, body perception and cognition; less in intensity and affect

(Riba et al., 2003)

Modest effects when compared to pure DMT

(Grob et al., 1996)
Possible Long-time Effects

Euthymia (psychic wellness)

“Anti-dependence” effect

Increase in self-knowledge
Health: Therapeutic use
Very preliminary results

Different settings
Healing centers with different approaches
Religious centers

What is “a cure”?
Mental health: Positive effects
Evidence of antidepressive effects in animal models
(Lima et al. 2006; 2007)

Reduction of anxiety symptoms
(Santos et al., 2007)

Open study:Anxiolytic and antidepressant effects in patients with depressive disorder.
(Osório et al., 2015)
Mental health: Antidepressants
Putative risk of serotonine syndrome
(Callaway e Grob, 1998)

Report of symptoms is less frequent and less severe than previously suggested
(Tófoli et al., unpublished data)
Unadvisable to offer ayahuasca to someone with a past history of severe mental disorder.

Avoid to offer ayahuasca to those under effect of other psychoactive substances.
Mental Health
Mental Health: Brazil’s rules
General
Biomedical Aspects
Is the available biomedical evidence for safety enough?
What are the determinants of the interpretation of biomedical data?
Which is - or shall be - the role of biomedical evidence in the regulation of ayahuasca?
AYAHUASCA REGULATION
RELIGIOUS FREEDOM AND HUMAN RIGHTS
POSITIVE EFFECTS IN SOCIETY
CONCEPTION OF RELIGION
PERCEPTION OF RISK TO PUBLIC HEALTH
THERAPEUTIC EFFECTS
DRUG POLICIES
GOVERNMENT IDEOLOGY
Segurança para a Saúde
A literatura científica aponta claramente para a segurança do uso da ayahuasca

(Grob et al., 1996; Gable, 2007; Halpern, 2008)
Possíveis Efeitos de Longo Prazo

Melhora da performance cognitiva

Eutimia (bem-estar psíquico)

Efeito “anti-dependência”
Saúde : Uso Terapêutico
Evidências preliminares

Deontologicamente, religiões da ayahuasca não podem ser “centros de tratamento”

Cura na religiões ayahuasqueiras
Mental Health: Risk of Psychosis
The risk of first episodes of psychosis within the UDV was compatible with the number of expected cases in the general population in a context of a "lay triage".

Cases can be reduced if people with antecedents of severe mental illness don't drink ayahuasca

However, the risk of psychotic outbreak without psychiatric antecedents do exist.

(Santos & Strassman, 2008; Lima e Tófoli, 2011)
LAW ENFORCEMENT
Moving forward to new research
Other health conditions
Cancer (Schenberg, 2013)
Parasites
Leishmania
(Di Giordio et al., 2004; Lala et al. 2004)
Plasmodium
(Astulla et al., 2008; Shahinas et al., 2012)
Toxoplasma (Alomar et al., 2013)
Worms (Rodriguez, 1982)
Parkinson's Disease (Serrano-Dueñas, 2001)
Therapeutic effects
Toxicological evidence for pregnant rats
(Oliveira et al, 2011)

Need for epidemiological studies with humans
Case-control
Cohort
Pregnancy and infancy
Case report or case follow-up within ayahuasquero groups

Animal studies

Focus: MAOis and SSRIs
Medications
Ayahuasca, dreams, meditation, visions

World recognition by mind and the structure of consciousness

The development or adaptation of shamanic/religious technology
Explorations
Respect to ayahuasca drinkers and their traditions.

Understanding that our understanding has limits

On being political activists
Before the end...
Controlled studies

Double-blinding ayahuasca

Ritual component is relevant - how to include it in clinical trials

Health systems/services research
Research questions
Banisteriopsis caapi
“REAL” RISK
luisfernandotofoli@gmail.com
Mental health
Substance misuse
(Liester & Prickett, 2012)

Depression
Anxiety disorders
Posttraumatic stress disorder
(Nielson & Megler, 2014)
Therapeutic effects
Schenberg, 2013
Experimental data
Harmine increases BDNF in rats
(Fortunato et al., 2010)

5HT-2a receptor may mediate BDNF expression
(Vaidya et al., 1997; Meller et al., 2002)

Harmine may have a dopaminergic ‘agonist therapeutic effect’ in the nucleus accumbens
(Brierley & Davidson, 2013)

Ayahuasca increased inhibitory amino acids in hippo-campus, decreased the utilization of MA in amygdala
(Castro-Neto, 2013)


Evidence from animal model
(Oliveira-Lima, 2015)
Full transcript