OPEN Foundation

Ayahuasca

Chemical Composition of Traditional and Analog Ayahuasca

Abstract

Traditional ayahuasca can be defined as a brew made from Amazonian vine Banisteriopsis caapi and Amazonian admixture plants. Ayahuasca is used by indigenous groups in Amazonia, as a sacrament in syncretic Brazilian religions, and in healing and spiritual ceremonies internationally. The study aimed to determine concentrations of the main bio- and psychoactive components of ayahuasca used in different locations and traditions. We collected 102 samples of brews from ayahuasca-using communities. Concentrations of N,N-dimethyltryptamine (DMT), tetrahydroharmine, harmine, and harmaline were determined by ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Qualitative analyses for non-traditional additives (moclobemide, psilocin, yuremamine) were performed by high resolution mass spectrometry. Higher and more variable concentrations of DMT in neoshamanic ayahuasca samples compared to indigenous samples may indicate use of higher and more variable proportions of DMT-containing admixture plants. From European samples, we found two related samples of analog ayahuasca containing moclobemide, psilocin, DMT, yuremamine, and very low concentrations of B. caapi alkaloids. Some analogs of ayahuasca (Peganum harmala, Mimosa tenuiflora) were used in Europe. No analogs were found from Brazil or Santo Daime ceremonies in Europe. We recommend awareness about the constituents of the brew and ethical self-regulation among practitioners of ayahuasca ceremonies.

Kaasik, H., Souza, R., Zandonadi, F. S., Tófoli, L. F., & Sussulini, A. (2021). Chemical Composition of Traditional and Analog Ayahuasca. Journal of psychoactive drugs, 53(1), 65–75. https://doi.org/10.1080/02791072.2020.1815911

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Remembering Jordi Riba – Pioneering ayahuasca researcher


We are deeply saddened by the loss of pharmacologist dr. Jordi Riba, probably the most prominent psychedelic researcher in Catalunya and Spain, and a true pioneer in the biomedical study of ayahuasca.
Jordi was a true explorer who conducted his scientific quest for discovery and information in the same way 15th-century discoverers explored territories on unknown continents: without navigation, but with great dedication and perseverance. He became intrigued by the effects of ayahuasca at a time when research into psychedelics was ignored by most of the scientific community, and actively opposed by governments in many countries. Despite these obstacles, he managed to bring ayahuasca to his Barcelona research clinic and published an unprecedented controlled, dose-ranging study on freeze-dried ayahuasca almost 20 years ago. Since then he has published close to 40 scientific research papers on ayahuasca, greatly advancing psychedelic research and significantly contributing to the re-emerging interest in therapeutic applications of psychedelics.
Jordi Riba was a prominent speaker at all previous editions of ICPR. The first time OPEN met with Jordi was in 2010, right before the Mind Altering Science conference. It was the first conference OPEN had ever organized. As novices in this field, we invited several experts, and to our own amazement, many of them, including Jordi, accepted our invitation. We even managed to find a hotel that would accommodate our speakers for free. Jordi Riba and his colleague José Carlos Bouso were the first to arrive in Amsterdam, and they headed directly to the hotel. Before long, they called us and stated politely but in no uncertain terms that thank you very much, we will not be staying here. Flabbergasted, we apologized and tried frantically to find an alternative hotel. Inexperienced as we were, we had not visited the hotel before accepting their offer, but sure enough, the “Hemp Hotel” was aimed at cannabis tourists; the shabby couches in the lobby were full of stoned tourists, the hemp smoke thick enough to cut with a knife, and the receptionist absolutely clueless that the hotel was reserved for our speakers. Luckily, we found them a decent hotel and by all accounts, the conference was a success. This anecdote was typical for Jordi – a polite and serious gentleman researcher from Spain who would not abide crappy hotels. He would go on to speak at all of our conferences throughout the years, and would have been present at ICPR 2020, had circumstances been different.
Looking back on fifteen years of ayahuasca research in an interview with OPEN, he shared many of the complexities – technically, culturally, and pharmacologically – of studying such a culturally embedded and variable plant mixture. To address some of these, he managed to create standardized, freeze-dried and encapsulated ayahuasca, which he administered to volunteers in various doses in his Barcelona lab. In addition to the pharmacodynamics and pharmacokinetics of ayahuasca, he used neuroimaging techniques to study the brew’s effects on humans, and used in vitro techniques to investigate the effects on a cellular level. At his last lecture at ICPR 2016, he presented ground-breaking findings, showing that the harmala alkaloids, harmine and tetrahydroharmine, induce neurogenesis, which not only provided further evidence that ayahuasca’s effects were due to more than just DMT, made available orally, but that the beta-carbolines present in the brew had important, therapeutically relevant effects of their own. It is unfortunate that throughout most of his career he conducted his research without much scientific support or resources while overall recognition of his work only emerged towards the end of his career. But Jordi accepted irony easily and embraced satire, as he was a man full of wit and humour. It’s quite telling that Don Quixote was among his favourite novels.
During the final years of his career Jordi resigned from Sant Pau Hospital while facing an existential crisis. He felt very lucky to be surrounded by warm-hearted family, friends and colleagues and had every intention to find his way back to academia. He loved the free haven of questioning and exploring minds, driven by curiosity, without prejudice, bias or agenda. Jordi Riba’s passing was sudden and tragic, and we can only remember his curiosity, scientific diligence and wry sense of humor with fondness. He will be sorely missed.

Psychedelic Treatments for Psychiatric Disorders: A Systematic Review and Thematic Synthesis of Patient Experiences in Qualitative Studies

Abstract

Introduction: Interest in the use of psychedelic substances for the treatment of mental disorders is increasing. Processes that may affect therapeutic change are not yet fully understood. Qualitative research methods are increasingly used to examine patient accounts; however, currently, no systematic review exists that synthesizes these findings in relation to the use of psychedelics for the treatment of mental disorders.

Objective: To provide an overview of salient themes in patient experiences of psychedelic treatments for mental disorders, presenting both common and diverging elements in patients’ accounts, and elucidating how these affect the treatment process.

Methods: We systematically searched the PubMed, MEDLINE, PsycINFO, and Embase databases for English-language qualitative literature without time limitations. Inclusion criteria were qualitative research design; peer-reviewed studies; based on verbalized patient utterances; and a level of abstraction or analysis of the results. Thematic synthesis was used to analyze and synthesize results across studies. A critical appraisal of study quality and methodological rigor was conducted using the Critical Appraisal Skills Programme (CASP).

Results: Fifteen research articles, comprising 178 patient experiences, were included. Studies exhibited a broad heterogeneity in terms of substance, mental disorder, treatment context, and qualitative methodology. Substances included psilocybin, lysergic acid diethylamide (LSD), ibogaine, ayahuasca, ketamine and 3,4-methylenedioxymethamphetamine (MDMA). Disorders included anxiety, depression, eating disorders, post-traumatic stress disorder, and substance use disorders. While the included compounds were heterogeneous in pharmacology and treatment contexts, patients reported largely comparable experiences across disorders, which included phenomenological analogous effects, perspectives on the intervention, therapeutic processes and treatment outcomes. Comparable therapeutic processes included insights, altered self-perception, increased connectedness, transcendental experiences, and an expanded emotional spectrum, which patients reported contributed to clinically and personally relevant responses.

Conclusions: This review demonstrates how qualitative research of psychedelic treatments can contribute to distinguishing specific features of specific substances, and carry otherwise undiscovered implications for the treatment of specific psychiatric disorders.

Breeksema, J. J., Niemeijer, A. R., Krediet, E., Vermetten, E., & Schoevers, R. A. (2020). Psychedelic treatments for psychiatric disorders: a systematic review and thematic synthesis of patient experiences in qualitative studies. CNS drugs, 1-22; 10.1007/s40263-020-00748-y

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Ayahuasca blocks the reinstatement of methylphenidate-induced conditioned place preference in mice: behavioral and brain Fos expression evaluations

Abstract

Rationale: Accumulating evidence suggests that ayahuasca, a hallucinogenic beverage used in traditional Amazonian communities for ritualistic and curative purposes, has been associated with reduced rates of substance use disorders. However, the brain mechanisms underlying the therapeutic effects of ayahuasca have not yet been fully elucidated.

Objectives: The aim of the present study was to investigate the effects of treatment with ayahuasca on the rewarding properties of the psychostimulant methylphenidate.

Methods: The rewarding properties of ayahuasca (100 mg/kg, orally) and methylphenidate (10 mg/kg, i.p.) were investigated using the conditioned place preference (CPP) model. Furthermore, we evaluated the effects of repeated treatment with ayahuasca on the reinstatement of methylphenidate-induced CPP. Fos expression was evaluated in different limbic structures (cingulate cortex-area 1, prelimbic cortex, infralimbic cortex, orbitofrontal cortex-lateral orbital area, nucleus accumbens core and shell, ventral tegmental area, dorsal striatum, and basolateral amygdala) upon each experimental phase.

Results: Both ayahuasca and methylphenidate induced CPP in mice. However, ayahuasca had limited effects on Fos expression, while methylphenidate altered Fos expression in several brain regions associated with the behavioral effects of drugs of abuse. Treatment with ayahuasca after conditioning with methylphenidate blocked the reinstatement of methylphenidate-induced CPP. Those behavioral effects were accompanied by changes in Fos expression patterns, with ayahuasca generally blocking the changes in Fos expression induced by conditioning with methylphenidate and/or reexposure to methylphenidate.

Conclusions: Our findings suggest that ayahuasca restored normal brain function in areas associated with the long-term expression of drug wanting/seeking in animals conditioned to methylphenidate.

Reis, H. S., Rodrigues, I., Anjos-Santos, A., Libarino-Santos, M., Serra, Y. A., Cata-Preta, E. G., Oliveira-Campos, D., Kisaki, N. D., Barros-Santos, T., Yokoyama, T. S., Cruz, F. C., Oliveira-Lima, A. J., Barbosa, P., Berro, L. F., & Marinho, E. (2020). Ayahuasca blocks the reinstatement of methylphenidate-induced conditioned place preference in mice: behavioral and brain Fos expression evaluations. Psychopharmacology, 237(11), 3269–3281. https://doi.org/10.1007/s00213-020-05609-6

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Modulatory effects of ayahuasca on personality structure in a traditional framework

Abstract

Ayahuasca is a psychoactive plant brew containing dimethyltryptamine (DMT) and monoamine oxidase inhibitors (MAOIs). It originates from the Amazon basin, where it is used primarily for ceremonial purposes. Ayahuasca tourists are now entering certain communities seeking alternative physical or psychological healing, as well as spiritual growth.

Rationale: Recent evidence has shown that the similar acting psychedelic compound, psilocybin, facilitated long-term increases in trait openness following a single administration.

Objectives: This paper assesses the impact of ayahuasca on personality in a traditional framework catering for ayahuasca tourists.

Method: Within a mixed design, we examined the effect of ayahuasca on participants’ personality (measured by the NEO Personality Inventory 3 questionnaire) across time (pre- to post-ayahuasca administration, and 6-month follow-up), relative to a comparison group (who did not ingest ayahuasca).

Results: The results demonstrated significant increases in agreeableness pre- and post-ayahuasca administration and significant reductions in neuroticism in 24 participants, relative to the comparison group. Both of these changes were sustained at 6-month follow-up, and trait level increases were also observed in openness at this stage. Additionally, greater perceived mystical experience (measured using the Mystical Experience Questionnaire 30) was associated with increased reductions in neuroticism.

Conclusions: These findings, which indicate a positive mediating effect of ayahuasca on personality, support the growing literature suggesting potential therapeutic avenues for serotonergic psychedelics.

Netzband, N., Ruffell, S., Linton, S., Tsang, W. F., & Wolff, T. (2020). Modulatory effects of ayahuasca on personality structure in a traditional framework. Psychopharmacology, 237(10), 3161–3171. https://doi.org/10.1007/s00213-020-05601-0

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Changes in inflammatory biomarkers are related to the antidepressant effects of Ayahuasca

Abstract

Background: Ayahuasca is a traditional Amazon brew and its potential antidepressant properties have recently been explored in scientific settings. We conducted a double-blind placebo-controlled trial of ayahuasca with treatment-resistant depression patients (n = 28) and healthy controls (n = 45).

Aims: We are evaluating the blood inflammatory biomarkers: C-reactive protein and interleukin 6, as a potential consequence of ayahuasca intake and their correlation with serum cortisol and brain-derived neurotrophic factor levels. Blood samples were collected at pre-treatment and 48 hours after substance ingestion to assess the concentration of inflammatory biomarkers, together with administration of the Montgomery-Åsberg Depression Rating Scale.

Results: At pre-treatment, patients showed higher C-reactive protein levels than healthy controls and a significant negative correlation between C-reactive protein and serum cortisol levels was revealed (rho = -0.40, n = 14). C-reactive protein in those patients was not correlated with Montgomery-Åsberg Depression Rating Scale scores. We observed a significant reduction of C-reactive protein levels across time in both patients and controls treated with ayahuasca, but not with placebo. Patients treated with ayahuasca showed a significant correlation (rho = + 0.57) between larger reductions of C-reactive protein and lower depressive symptoms at 48 hours after substance ingestion (Montgomery-Åsberg Depression Rating Scale). No significant result with respect to interleukin 6 and brain-derived neurotrophic factor was found. Furthermore, these biomarkers did not predict the antidepressant response or remission rates observed.

Conclusions: These findings enhance the understanding of the biological mechanisms behind the observed antidepressant effects of ayahuasca and encourage further clinical trials in adults with depression.

Galvão-Coelho, N. L., de Menezes Galvão, A. C., de Almeida, R. N., Palhano-Fontes, F., Campos Braga, I., Lobão Soares, B., … & de Araujo, D. B. (2020). Changes in inflammatory biomarkers are related to the antidepressant effects of Ayahuasca. Journal of Psychopharmacology34(10), 1125-1133; 10.1177/0269881120936486
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The pharmacological interaction of compounds in ayahuasca: a systematic review

Abstract

Ayahuasca is a South American psychoactive plant brew used as traditional medicine in spiritual and in cultural rituals. This is a review of the current understanding about the pharmacological mechanisms that may be interacting in ayahuasca. Searches were performed using PubMed, PsycINFO, and Web of Science databases and 16 papers were selected. As hypothesized, the primary narrative in existing research revolved around prevention of deamination of N,N-dimethyltryptamine (N,N-DMT, also referred to as DMT) by monoamine oxidase inhibitors (MAOIs) in ayahuasca. Two of the constituents, DMT and harmine, have been studied more than the secondary harmala alkaloids. At present, it is unclear whether the pharmacological interactions in ayahuasca act synergistically or additively to produce psychoactive drug effects. The included studies suggest that our current understanding of the preparation’s synergistic mechanisms is limited and that more complex processes may be involved; there is not yet enough data to determine any potential synergistic interaction between the known compounds in ayahuasca. Our pharmacological understanding of its compounds must be increased to avoid the potential risks of ayahuasca use.

Ruffell, S., Netzband, N., Bird, C., Young, A. H., & Juruena, M. F. (2020). The pharmacological interaction of compounds in ayahuasca: a systematic review. Brazilian Journal of Psychiatry42(6), 646-656.; 10.1590/1516-4446-2020-0884
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Spotlight commentary: REBUS and the anarchic brain

Abstract

In ‘REBUS and the Anarchic Brain: Towards a Unified Model of the Brain Action of Psychedelics’, Carhart-Harris and Friston offer an important analysis of what the predictive processing framework has to offer our understanding of psychedelic experiences, providing an invaluable ground for psychedelic psychiatry. While applauding this, we encourage paying greater attention to contextual factors shaping extreme experiences and their sequalae, and suggest that the authors’ comparisons with certain non-psychedelic altered states may overlook more informative parallels that can be drawn elsewhere. Addressing both points will prove fruitful, ultimately, in identifying the mechanisms of action of greatest interest in psychedelic experiences.
Carhart-Harris, R. L., & Friston, K. J. (2019). REBUS and the anarchic brain: toward a unified model of the brain action of psychedelics. Pharmacological reviews71(3), 316-344., https://doi.org/10.1093/nc/niaa007
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A Meta-Analysis of Placebo-Controlled Trials of Psychedelic-Assisted Therapy

Abstract

After a two-decade hiatus in which research on psychedelics was essentially halted, placebo-controlled clinical trials of psychedelic-assisted therapy for mental health conditions have begun to be published. We identified nine randomized, placebo-controlled clinical trials of psychedelic-assisted therapy published since 1994. Studies examined psilocybin, LSD (lysergic acid diethylamide), ayahuasca (which contains a combination of N,N-dimethyltryptamine and harmala monoamine oxidase inhibitor alkaloids), and MDMA (3,4-methylenedioxymethamphetamine). We compared the standardized mean difference between the experimental and placebo control group at the primary endpoint. Results indicated a significant mean between-groups effect size of 1.21 (Hedges g), which is larger than the typical effect size found in trials of psychopharmacological or psychotherapy interventions. For the three studies that maintained a placebo control through a follow-up assessment, effects were generally maintained at follow-up. Overall, analyses support the efficacy of psychedelic-assisted therapy across four mental health conditions – post-traumatic stress disorder, anxiety/depression associated with a life-threatening illness, unipolar depression, and social anxiety among autistic adults. While study quality was high, we identify several areas for improvement regarding the conduct and reporting of trials. Larger trials with more diverse samples are needed to examine possible moderators and mediators of effects, and to establish whether effects are maintained over time.
Luoma, J. B., Chwyl, C., Bathje, G. J., Davis, A. K., & Lancelotta, R. (2020). A Meta-analysis of Placebo-controlled Trials of Psychedelic-assisted Therapy. Journal of Psychoactive Drugs, 1-11., https://doi.org/10.1080/02791072.2020.1769878
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Mystical Experiences in Retrospective Reports of First Times Using a Psychedelic in Finland

Abstract

Despite their acutely inebriating and sometimes unpleasant effects, some people report positive changes in life satisfaction, well-being, or mental health after taking psychedelic drugs. One explanation may be the ability of psychedelics to trigger mystical-type experiences. We examined the validity, reliability, and factor structure of a novel Finnish translation of the Revised Mystical Experiences Questionnaire (MEQ30) among 288 people retrospectively reporting on their first time using a psychedelic. We found evidence for internal consistency reliability and preliminary evidence for criterion and discriminant validity of the Finnish MEQ30. A four-factor structure with factors for mystical qualities, positive mood, transcendence, and ineffability had the best, fair to reasonable fit to the data. MEQ30 scores and having a full mystical experience were highly associated with describing the experience as mystical, spiritual, or religious, and as personally significant, and somewhat associated with the experience being sad or difficult. Mystical experiences were especially associated with positive changes in relationships with nature and oneself and in creativity. Mystical experiences were more common with larger doses. Increasing research suggests mystical-type experiences to relate to positive changes after taking psychedelics. The Finnish MEQ30 is able to tap into relevant information about this aspect of people’s psychedelic experiences.
Kangaslampi, S., Hausen, A., & Rauteenmaa, T. (2020). Mystical Experiences in Retrospective Reports of First Times Using a Psychedelic in Finland. Journal of Psychoactive Drugs, 1-10. https://doi.org/10.1080/02791072.2020.1767321
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30 April - Q&A with Rick Strassman

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