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      Adverse effects of ayahuasca: Results from the Global Ayahuasca Survey

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          Abstract

          Introduction

          Ayahuasca is a plant-based decoction native to Amazonia, where it has a long history of use in traditional medicine. Contemporary ritual use of ayahuasca has been expanding throughout the world for mental health purposes, and for spiritual and personal growth. Although researchers have been conducting clinical trials and observational studies reporting medical and psychological benefits, most of these do not report ayahuasca’s immediate or medium-term adverse effects, so these are underrepresented in the literature. With the expansion of ayahuasca ceremonies from their traditional contexts to countries around the world, there is an important public health question regarding the risk/benefit balance of its use.

          Methods

          We used data from an online Global Ayahuasca Survey (n = 10,836) collected between 2017 and 2019 involving participants from more than 50 countries. Principal component analysis was performed to assess group effects. Logistic regression analysis was performed to test for adverse effects associated with history of ayahuasca use, clinical, context of use and spiritual effect variables.

          Results

          Acute physical health adverse effects (primarily vomiting) were reported by 69.9% of the sample, with 2.3% reporting the need for subsequent medical attention. Adverse mental health effects in the weeks or months following consumption were reported by 55.9% of the sample, however, around 88% considered such mental health effects as part of a positive process of growth or integration. Around 12% sought professional support for these effects. Physical adverse effects were related to older age at initial use of ayahuasca, having a physical health condition, higher lifetime and last year ayahuasca use, having a previous substance use disorder diagnosis, and taking ayahuasca in a non-supervised context. Mental health adverse effects were positively associated with anxiety disorders; physical health conditions; and the strength of the acute spiritual experience; and negatively associated with consumption in religious settings.

          Conclusions

          While there is a high rate of adverse physical effects and challenging psychological effects from using ayahuasca, they are not generally severe, and most ayahuasca ceremony attendees continue to attend ceremonies, suggesting they perceive the benefits as outweighing any adverse effects. Knowing what variables might predict eventual adverse effects may serve in screening of, or providing additional support for, vulnerable subjects. Improved understanding of the ayahuasca risk/benefit balance can also assist policy makers in decisions regarding potential regulation and public health responses.

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          Most cited references75

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          An ultra-brief screening scale for anxiety and depression: the PHQ-4.

          The most common mental disorders in both outpatient settings and the general population are depression and anxiety, which frequently coexist. Both of these disorders are associated with considerable disability. When the disorders co-occur, the disability is even greater. Authors sought to test an ultra-brief screening tool for both. Validated two-item ultra-brief screeners for depression and anxiety were combined to constitute the Patient Health Questionnaire for Depression and Anxiety (the PHQ-4). Data were analyzed from 2,149 patients drawn from 15 primary-care clinics in the United States. Factor analysis confirmed two discrete factors (Depression and Anxiety) that explained 84% of the total variance. Increasing PHQ-4 scores were strongly associated with functional impairment, disability days, and healthcare use. Anxiety had a substantial effect on functional status that was independent of depression. The PHQ-4 is a valid ultra-brief tool for detecting both anxiety and depressive disorders.
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            An Ultra-Brief Screening Scale for Anxiety and Depression: The PHQ–4

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              Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

              Background Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. Methods To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing. Results We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054). Conclusions To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLOS Glob Public Health
                PLOS Glob Public Health
                plos
                PLOS Global Public Health
                Public Library of Science (San Francisco, CA USA )
                2767-3375
                16 November 2022
                2022
                : 2
                : 11
                : e0000438
                Affiliations
                [1 ] International Center for Ethnobotanical Education, Research and Services (ICEERS), Barcelona, Spain
                [2 ] Medical Anthropology Research Center, Department of Anthropology, Philosophy and Social Work, University of Rovira I Virgili, Tarragona, Spain
                [3 ] Department of Neurosciences and Behavior, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
                [4 ] Research Sherpas, Mieres (Olot), Sabadell, Spain
                [5 ] Psychae Institute, Melbourne, Australia
                [6 ] NICM Health Research Institute, Western Sydney University, Westmead, Australia
                [7 ] Florey Institute of Neuroscience and Mental Health, The Melbourne Clinic Professorial Unit, Department of Psychiatry, University of Melbourne, Melbourne, Australia
                [8 ] Department of Psychiatry, Psychotherapy, and Psychosomatics, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
                [9 ] Interdisciplinary Cooperation for Ayahuasca Research and Outreach (ICARO), School of Medical Sciences, University of Campinas, Campinas, Brazil
                [10 ] Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil
                [11 ] School of Social and Political Science, University of Melbourne, Melbourne, Australia
                [12 ] School of Population and Global Health, University of Melbourne, Melbourne, Australia
                [13 ] Centre for Mental Health, Swinburne University, Melbourne, Australia
                PLOS: Public Library of Science, UNITED STATES
                Author notes

                JS and DP are directors of a not-for-profit medicinal psychedelics research institute, Psychae Institute, which has received funding from the biotechnology sector. There are no patents or marketed products associated with this research to declare. This does not alter our adherence to PLOS policies on sharing data and materials.

                Author information
                https://orcid.org/0000-0003-1115-9407
                https://orcid.org/0000-0002-9663-3632
                https://orcid.org/0000-0002-2055-1649
                Article
                PGPH-D-21-01050
                10.1371/journal.pgph.0000438
                10021266
                36962494
                43cd3f62-205a-436c-9206-2eb983f0b6d8
                © 2022 Bouso et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 1 December 2021
                : 7 October 2022
                Page count
                Figures: 0, Tables: 6, Pages: 25
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Research and Analysis Methods
                Research Design
                Clinical Research Design
                Adverse Events
                Social Sciences
                Anthropology
                Cultural Anthropology
                Religion
                Social Sciences
                Sociology
                Religion
                Medicine and Health Sciences
                Epidemiology
                Medical Risk Factors
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                Mental Health and Psychiatry
                Neuropsychiatric Disorders
                Anxiety Disorders
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                Neuroses
                Anxiety Disorders
                Biology and Life Sciences
                Psychology
                Emotions
                Social Sciences
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                Emotions
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                Mental Health and Psychiatry
                Mood Disorders
                Depression
                Biology and Life Sciences
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                Cognitive Psychology
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                Custom metadata
                The datasets presented in this article are not readily available because Ethics approval and consent signed by participants was for data access by research team members only. Requests to access the datasets would require a new Ethics submission and should be directed to HumanEthics-Enquiries@ 123456unimelb.edu.au .

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