Overcoming epistemic injustices in the biomedical study of ayahuasca: Towards ethical and sustainable regulation.

After decades of biomedical research on ayahuasca's molecular compounds and their physiological effects, recent clinical trials show evidence of therapeutic potential for depression. However, indigenous peoples have been using ayahuasca therapeutically for a very long time, and thus we question the epistemic authority attributed to scientific studies, proposing that epistemic injustices were committed with practical, cultural, social, and legal consequences. We question epistemic authority based on the double-blind design, the molecularization discourse, and contextual issues about safety. We propose a new approach to foster epistemically fair research, outlining how to enforce indigenous rights, considering the Brazilian, Peruvian, and Colombian cases. Indigenous peoples have the right to maintain, control, protect, and develop their biocultural heritage, traditional knowledge, and cultural expressions, including traditional medicine practices. New regulations about ayahuasca must respect the free, prior, and informed consent of indigenous peoples according to the International Labor Organization Indigenous and Tribal Peoples Convention no. 169. The declaration of the ayahuasca complex as a national cultural heritage may prevent patenting from third parties, fostering the development of traditional medicine. When involving isolated compounds derived from traditional knowledge, benefit-sharing agreements are mandatory according to the United Nations' Convention on Biological Diversity. Considering the extremely high demand to treat millions of depressed patients, the medicalization of ayahuasca without adequate regulation respectful of indigenous rights can be detrimental to indigenous peoples and their management of local environments, potentially harming the sustainability of the plants and of the Amazon itself, which is approaching its dieback tipping point.

Psychedelic-Assisted Psychotherapy: A Paradigm Shift in Psychiatric Research and Development.

Mental disorders are rising while development of novel psychiatric medications is declining. This stall in innovation has also been linked with intense debates on the current diagnostics and explanations for mental disorders, together constituting a paradigmatic crisis. A radical innovation is psychedelic-assisted psychotherapy (PAP): professionally supervised use of ketamine, MDMA, psilocybin, LSD and ibogaine as part of elaborated psychotherapy programs. Clinical results so far have shown safety and efficacy, even for "treatment resistant" conditions, and thus deserve increasing attention from medical, psychological and psychiatric professionals. But more than novel treatments, the PAP model also has important consequences for the diagnostics and explanation axis of the psychiatric crisis, challenging the discrete nosological entities and advancing novel explanations for mental disorders and their treatment, in a model considerate of social and cultural factors, including adversities, trauma, and the therapeutic potential of some non-ordinary states of consciousness.

Translation and cultural adaptation of the States of Consciousness Questionnaire (SOCQ) and statistical validation of the Mystical Experience Questionnaire (MEQ30) in Brazilian Portuguese

Abstract Background The States of Consciousness Questionnaire (SOCQ) was developed to assess the occurrence features of the change in consciousness induced by psilocybin, and includes the Mystical Experience Questionnaire (MEQ), developed to assess the ocurrence of mystical experiences in altered states of consciousness. Objective To translate the SOCQ to Brazilian Portuguese and validate the 30-item MEQ. Methods The SOCQ was translated to Brazilian Portuguese and backtranslated into English. The two English versions were compared and differences corrected, resulting in a Brazilian translation. Using an internet-survey, 1504 Portuguese-speaking subjects answered the translated version of the SOCQ. The 4-factor version of MEQ30 was analyzed using confirmatory factor analysis and reliability analysis. Results A Brazilian Portuguese version of the SOCQ was made available. Goodness-of-fit indexes indicated that data met the factorial structure proposed for the English MEQ30. Factors presented excellent to acceptable reliability according to Cronbach’s alpha: mystical (0.95); positive mood (0.71); transcendence of time/space (0.83); and ineffability (0.81). Discussion The Brazilian Portuguese version of the MEQ30 is validated and it fits in the factorial structure performed on the original English version. The SOCQ is also available to the Brazilian Portuguese speaking population, allowing studies in different languages to be conducted and compared systematically.

Acute Biphasic Effects of Ayahuasca.

Ritual use of ayahuasca, an amazonian Amerindian medicine turned sacrament in syncretic religions in Brazil, is rapidly growing around the world. Because of this internationalization, a comprehensive understanding of the pharmacological mechanisms of action of the brew and the neural correlates of the modified states of consciousness it induces is important. Employing a combination of electroencephalogram (EEG) recordings and quantification of ayahuasca's compounds and their metabolites in the systemic circulation we found ayahuasca to induce a biphasic effect in the brain. This effect was composed of reduced power in the alpha band (8-13 Hz) after 50 minutes from ingestion of the brew and increased slow- and fast-gamma power (30-50 and 50-100 Hz, respectively) between 75 and 125 minutes. Alpha power reductions were mostly located at left parieto-occipital cortex, slow-gamma power increase was observed at left centro-parieto-occipital, left fronto-temporal and right frontal cortices while fast-gamma increases were significant at left centro-parieto-occipital, left fronto-temporal, right frontal and right parieto-occipital cortices. These effects were significantly associated with circulating levels of ayahuasca's chemical compounds, mostly N,N-dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine and some of their metabolites. An interpretation based on a cognitive and emotional framework relevant to the ritual use of ayahuasca, as well as it's potential therapeutic effects is offered.

Treating drug dependence with the aid of ibogaine: a retrospective study.

Ibogaine is an alkaloid purported to be an effective drug dependence treatment. However, its efficacy has been hard to evaluate, partly because it is illegal in some countries. In such places, treatments are conducted in underground settings where fatalities have occurred. In Brazil ibogaine is unregulated and a combined approach of psychotherapy and ibogaine is being practiced to treat addiction. To evaluate the safety and efficacy of ibogaine, we conducted a retrospective analysis of data from 75 previous alcohol, cannabis, cocaine and crack users (72% poly-drug users). We observed no serious adverse reactions or fatalities, and found 61% of participants abstinent. Participants treated with ibogaine only once reported abstinence for a median of 5.5 months and those treated multiple times for a median of 8.4 months. This increase was statistically significant (p < 0.001), and both single or multiple treatments led to longer abstinence periods than before the first ibogaine session (p < 0.001). These results suggest that the use of ibogaine supervised by a physician and accompanied by psychotherapy can facilitate prolonged periods of abstinence, without the occurrence of fatalities or complications. These results suggest that ibogaine can be a safe and effective treatment for dependence on stimulant and other non-opiate drugs.

Caracterização eletrofisiológica da circuitaria hipocampal durante o ciclo sono-vigília do rato / Electrophysiological characterization of the hippocampal circuitry during the sleep-wake cycle of the rat

Estrutura central do hipocampo, o corno de Ammon pode ser subdividido em pelo menos três áreas: CA1, CA2 e CA3. Enquanto CA1 e CA3 foram extensamente estudados, dado o envolvimento do hipocampo em processos cognitivos como a memória e patológicos como a epilepsia, CA2 tem sido largamente ignorado na literatura. Entretanto, este campo possui características específicas, tanto neuroanatômicas como bioquímicas e fisiológicas, sendo resistente à indução de plasticidade e recebendo aferência específica do núcleo supramamilar do hipotálamo, envolvido na circuitaria geradora/mantenedora do ritmo teta, oscilações centrais ao funcionamento do hipocampo. O objetivo deste estudo foi, portanto, caracterizar no animal em livre movimentação os padrões de atividade eletrofisiológica nas três áreas do corno de Ammon bilateralmente. Os resultados demonstraram que CA2 possui, em média, intervalos entre disparos mais prolongados que CA1 e CA3 durante o sono de ondas lentas e o sono REM. Nestas fases do ciclo a coerência entre CA1-CA2 foi mais elevada que entre CA1-CA3 e CA2-CA3 nos três ratos avaliados, em três faixas de freqüência: teta (6 a 12 Hz), gama lento (30 a 50 Hz) e gama rápido (90 a 110 Hz) ipsilateralmente. A coerência entre campos contralaterais é predominante no teta, sendo quase zero nas demais freqüências. Estes resultados corroboram trabalhos recentes que apontam CA2 como área distinta e sugerem que esta pequena região do corno de Ammon possa exercer papéis importantes na modulação da atividade das demais estruturas hipocampais e parahipocampais em processos de memória e em patologias como a epilepsia

The Ammons horn, central structure of the hippocampus, can be subdivided in at least three regions: CA1, CA2 and CA3. While CA1 and CA3 have been extensively studied given the hippocampus involvement in cognitive processes such as memory and pathological ones such as epilepsy, CA2 remains largely ignored. However, this sector contains specific neuroanatomical, biochemical e physiological characteristics, being resistant to induction of plasticity and receiving a specific afference from the supramammillary nucleus in the hypothalamus, involved in the generation/maintenance of the theta rhythm, central oscillations to hippocampal functioning. Therefore, the objective of this study was to characterize electrophysiological patterns of interaction in the three areas of the Ammons horn bilaterally. Results revealed that CA2 has a mean interspike interval larger than CA1 and CA3 during slow wave and REM sleep. During these stages of the sleep-wake cycle, coherence between CA1-CA2 was higher than CA1-CA3 and CA2-CA3 in the three animals evaluated, in three frequency bands: theta (6 to 12 Hz), slow gamma (30 to 50 Hz) and fast gamma (90 to 110 Hz) ipsilaterally. Coherence between contralateral fields was predominant in the theta band and almost zero in other frequencies. These results add to some previous published data showing that CA2 is distinct from the other subfields and that this small region of the Ammons horn may exert important roles in modulating activity in the other hippocampal fields and parahippocampal regions during memory and pathologies such as epilepsy

Effects of pre or posttraining dorsal hippocampus D-AP5 injection on fear conditioning to tone, background, and foreground context.

NMDA receptor antagonist D-AP5 was injected into the dorsal hippocampus of Wistar rats before or immediately after the training session in fear conditioning. Training was conducted both with signaled (background context) or unsignaled (foreground context) footshocks. Contextual fear conditioning was assessed 24 h later and tone fear conditioning 48 h after training (only in the signaled footshock condition). Pretraining injections impaired conditioned fear to contextual features, both in background and foreground configurations, whereas tone fear conditioning was left intact. Posttraining injections were ineffective in all cases. We conclude that dorsal hippocampal NMDA receptors are required for contextual fear acquisition independently of context saliency and that they are not required to early consolidation processes.

Effects of pre- or post-training entorhinal cortex AP5 injection on fear conditioning.

Fear conditioning is one of the most studied paradigms to assess the neural basis of emotional memory. The circuitry involves NMDA receptor activation in the amygdala and, in the case of contextual conditioning, in the hippocampus. Entorhinal cortex is one of the major input/output structures to the hippocampus and also projects to the amygdala, both through glutamatergic transmission. Other learning tasks involving hippocampus and amygdala, such as inhibitory avoidance, require entorhinal cortex during acquisition and consolidation. However, the involvement of NMDA receptors mediated transmission in entorhinal cortex in fear conditioning acquisition and consolidation is not clear. To investigate that issue, rats were trained in fear conditioning to both contextual and tone conditioned stimulus. Immediately before, immediately, 30 or 90 min after training they received NMDA antagonist AP5 or saline injections bilaterally in the entorhinal cortex (AP-6.8 mm, L +/-5.0 mm DV-6.8 mm). Contextual fear conditioning was measured 24 h after training, and tone fear conditioning 48 h after training. AP5 injections selectively impaired contextual fear conditioning only when injected pre-training. Post-training injections had no effect. These findings suggest that entorhinal cortex NMDA receptors are necessary for acquisition, but not for consolidation, of contextual fear conditioning. On the other hand, both acquisition and consolidation of tone fear conditioning seem to be independent of NMDA receptors in the entorhinal cortex.