In recent years, ayahuasca—a traditional South American psychedelic brew—has emerged as a focal point of scientific inquiry into novel treatments for mental health disorders. While mounting evidence illustrates its therapeutic promise, a newly published comprehensive study in PLOS Mental Health unveils a far more nuanced picture, emphasizing how individual histories and ceremonial contexts critically shape its long-term psychological impacts. This groundbreaking research by an international team led by Óscar Andión, José Carlos Bouso, and Daniel Perkins employs sophisticated machine learning methods alongside classical statistics to analyze data from over ten thousand ayahuasca users worldwide, revealing key mediators of both beneficial and adverse mental health outcomes.
Ayahuasca has long been revered by Indigenous Amazonian peoples for its purported spiritual and healing properties. Its psychoactive effects arise primarily from the combination of N,N-Dimethyltryptamine (DMT) and monoamine oxidase inhibitors (MAOIs) present in the brew’s constituent plants. The resurgence of interest among Western clinicians and researchers has prompted considerable investigation into its ability to alleviate symptoms of depression, anxiety, and trauma-related disorders. However, until now, there has been a striking paucity of large-scale research focusing on the potential risks, particularly the adverse psychological experiences some users report.
This latest study draws on the extensive Global Ayahuasca Survey (GAS), a substantial dataset amassed through voluntary self-report from over 10,000 participants worldwide, including a final analytic sample of 5,400 individuals with complete data. Notably, 14.2% of these respondents reported a history of anxiety disorders, while nearly 20% disclosed past depressive disorders, providing a crucial lens into the interaction of prior mental health and ayahuasca’s psychological effects. The researchers acknowledge limitations inherent in the dataset, including self-selection bias and the retrospective nature of survey responses, which may span across years post-experience.
A salient finding of this multifaceted analysis is the influence of set and setting—the psychological state and physical/social environment at the time of consumption—on both immediate adverse experiences and subsequent mental health trajectories. Participants with preexisting anxiety or depression, particularly those who consumed ayahuasca outside traditional Indigenous or community-based ceremonies, demonstrated a markedly higher likelihood of negative psychological responses. These adverse reactions ranged from visual hallucinations to profound feelings of disconnection, loneliness, or even energetic hostility, underscoring the complex phenomenology of ayahuasca experiences.
Intriguingly, not all adverse effects portended poorer outcomes. Visual distortions—often regarded as hallmark effects of psychedelic states—were paradoxically associated with improved mental health metrics during follow-up. This counterintuitive association suggests that certain challenging experiences, while initially distressing, might embody therapeutic cognitive restructuring or emotional processing. Conversely, more affective adverse states, such as feeling “down,” isolated, or psychologically attacked, correlated strongly with long-term negative mental health consequences.
The study thus challenges reductive interpretations of ayahuasca’s adverse effects, advocating for a more refined conceptualization that distinguishes between phenomenologically distinct experiences and their differential prognostic implications. This differentiation is pivotal for clinicians, facilitators, and users alike, highlighting the critical need for adequate psychological preparation, skilled guidance, and supportive integration practices to optimize therapeutic benefit and mitigate harm.
Another dimension elucidated by the research is the protective role of spiritual and communal contexts. Ceremonial settings steeped in cultural traditions ostensibly provide a framework that buffers against adverse emotional states, fostering meaning-making and psychological resilience. Researchers emphasize that the communal nature of ayahuasca consumption—often undertaken in group rituals led by experienced shamans or facilitators—may catalyze both healing and integration, factors that are difficult to replicate in isolated or decontextualized Western clinical applications.
The implications for psychedelic medicine are profound. As ayahuasca and related compounds gain footholds in modern psychiatric care, this study underscores that pharmacology alone cannot account for patient outcomes. Instead, a biopsychosocial model that integrates individual mental health history, environmental context, and sociocultural factors will be essential. The findings also caution against indiscriminate use, particularly among vulnerable populations lacking access to appropriate supervision and community support.
Lead author Dr. José Carlos Bouso underscored this vital point: “What stood out most to us was the significant difference in mental health outcomes between users who had supportive environments during their use and those who didn’t. This emphasizes the importance of a responsible and well-prepared setting for those seeking healing through ayahuasca.” His remarks encapsulate the necessity for therapeutic frameworks that prioritize setting over mere pharmacological intervention.
The study’s authors also highlight the role of “challenging” psychological states traditionally stigmatized as strictly negative. They posit that such post-ayahuasca states may paradoxically act as catalysts for mental health improvements, particularly for those with prior anxiety and depression. These findings advocate for a paradigm shift in psychedelic research and clinical practice, moving away from binary classifications of “adverse” versus “beneficial” effects toward a more nuanced understanding of the psychedelic experience as a dynamic, context-dependent process.
To build on this foundation, the researchers call for future investigations that examine ayahuasca’s effects within naturalistic, communal settings common to Indigenous and neo-shamanic traditions. They argue that such ecological validity is crucial to unpacking the interplay between ceremony, spirituality, social support, and individual psychology, all of which appear to coalesce in shaping patient outcomes.
Moreover, the utilization of advanced machine learning techniques in parsing the GAS data exemplifies a methodological leap in psychedelic science. By identifying complex interactions among variables that traditional statistics might overlook, the study paves the way for precision medicine approaches that can tailor psychedelic therapies to individual profiles, mitigating risks and amplifying therapeutic potential.
The ethical landscape surrounding ayahuasca research also warrants attention. While the therapeutic prospects are promising, the authors disclose relevant competing interests: two co-authors hold equity and leadership roles in Psychae Therapeutics, a commercial entity investigating psychedelic compounds. Transparency regarding such conflicts is crucial to maintain trust and scientific rigor in this rapidly evolving field.
In the context of increasing medicalization of psychedelics globally, this study brings a timely reminder that ayahuasca’s traditional usage embedded within cultural and spiritual paradigms may hold key insights into its effective and safe application. Western biomedical frameworks must thus engage respectfully and collaboratively with Indigenous knowledge systems to harness ayahuasca’s potential responsibly.
Finally, as the psychedelic renaissance unfolds, this research advocates for careful delineation of who might benefit most from ayahuasca use and under what conditions. Individuals with mental health vulnerabilities require dedicated support structures alongside careful preparation and integration to avoid adverse outcomes and realize lasting improvements. This emphasis on context, history, and support forms a critical pillar in advancing ayahuasca from ethnobotanical curiosity into a viable, safe component of modern mental health therapeutics.
Subject of Research: The mediating role of individual mental health history and ceremonial context on the long-term psychological effects of ayahuasca use.
Article Title: A new insight into ayahuasca’s adverse effects: Reanalysis and perspectives on its mediating role in mental health from the Global Ayahuasca Survey (GAS).
News Publication Date: April 30, 2025
Web References:
References:
Andión Ó, Bouso JC, Sarris JJ, Tófoli LF, Opaleye ES, Perkins D (2025) A new insight into ayahuasca’s adverse effects: Reanalysis and perspectives on its mediating role in mental health from the Global Ayahuasca Survey (GAS). PLOS Mental Health 2(4): e0000097.
Image Credits: ICEERS, CC-BY 4.0
Keywords: Mental health, clinical psychology, ayahuasca, psychedelics, anxiety, depression, adverse effects, traditional medicine, therapeutic setting, spirituality
