The New England journal of medicine
November 3, 2022
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
1,095 citations
A single 25 mg dose of psilocybin, but not 10 mg, reduced depression scores more than a 1 mg control dose over three weeks in adults with treatment-resistant depression. In this phase 2 trial, 233 participants were randomly assigned to 25 mg, 10 mg, or 1 mg of synthetic psilocybin with psychological support. The 25 mg group showed an average 12-point drop on the MADRS depression scale versus a 5.4-point drop in the 1 mg group, a significant difference. The 10 mg group did not differ significantly from control. Response and remission rates at three weeks supported the primary result, but sustained response at 12 weeks was not significantly different.
The International Journal of Neuropsychopharmacology
October 21, 2022
James J Gattuso, Daniel Perkins, Simon Ruffell et al.
233 citations
Classical psychedelics like LSD, psilocybin, and ayahuasca consistently disrupt resting-state connectivity within the Default Mode Network (DMN) and increase functional connectivity between canonical resting-state networks. The DMN, a set of brain regions active during self-referencing and mind wandering, is altered in various neuropsychiatric conditions. While DMN modulation is central to some cognitive models of psychedelics, its role in their therapeutic potential remains unclear. This systematic review provides a comprehensive overview to guide future research on the neurocognitive mechanisms of these agents.
Frontiers in Psychiatry
June 9, 2021
Simon Ruffell, Nige Netzband, WaiFung Tsang et al.
74 citations
A naturalistic study of 63 people who participated in ayahuasca ceremonies at a retreat in the Peruvian Amazon found significant improvements in depression, anxiety, and overall psychological distress, along with increased self-compassion, immediately after the retreat and sustained at six months. Depression scores on the Beck Depression Inventory dropped from 13.9 to 6.1, anxiety scores on the State-Trait Anxiety Inventory fell from 44.4 to 34.3, and scores on the Clinical Outcomes in Routine Evaluation-Outcome Measure decreased from 37.3 to 22.3. Changes in memory valence were linked to these improvements. Epigenetic results were inconclusive but suggested further research on the SIGMAR1 gene is warranted.
Psychopharmacology
July 23, 2020
Nige Netzband, Simon Ruffell, Sabriya Linton et al.
56 citations
Ayahuasca, a psychoactive brew containing DMT and MAOIs, is traditionally used ceremonially in the Amazon and increasingly by tourists seeking healing or spiritual growth. In a mixed-design study, 24 participants who ingested ayahuasca showed significant increases in agreeableness and reductions in neuroticism compared to a control group, with changes sustained at a 6-month follow-up; trait openness also increased at follow-up. Greater perceived mystical experience was linked to larger reductions in neuroticism. These results suggest a positive mediating effect of ayahuasca on personality, supporting potential therapeutic uses for serotonergic psychedelics.
Brazilian Journal of Psychiatry
July 3, 2020
Simon Ruffell, Nige Netzband, Catherine Bird et al.
43 citations
Ayahuasca, a South American psychoactive plant brew used in traditional spiritual and cultural rituals, has been studied primarily for the prevention of deamination of N,N-dimethyltryptamine (DMT) by monoamine oxidase inhibitors (MAOIs) in the brew. Two constituents, DMT and harmine, have received more research attention than secondary harmala alkaloids. Current evidence suggests that the pharmacological interactions in ayahuasca may act synergistically or additively to produce psychoactive effects, but the understanding of these synergistic mechanisms is limited and more complex processes may be involved. There is not yet enough data to determine any potential synergistic interaction between the known compounds, and increased pharmacological understanding is needed to avoid potential risks.
Journal of Psychedelic Studies
March 29, 2019
Tom Wolff, Simon Ruffell, Nigel Netzband et al.
41 citations
In a study of nine foreign tourists at an ayahuasca retreat in Peru, the typical structure of spontaneously reported experiences included personal preparation, physical symptoms, visual phenomena, cognitive and emotional phenomena, reactions within the psychedelic world and ordinary reality, and appraisal of the process. Emotional reactions ranged from pleasant (psychotherapeutic target emotions and hedonistic emotions) to unpleasant. For most participants, the presence of psychotherapeutic target emotions seemed to involve unpleasant emotions in the same session, possibly as transitional emotional states. This suggests psychodynamic processes, such as activation of emotional conflicts, can occur spontaneously during ayahuasca intake in this setting. Some participants attributed symbolic meaning to visionary content, more likely among psychotherapeutically motivated clients. The setting and expectations about native wisdom may influence experiences and interpretations.
Frontiers in Neuroscience
January 31, 2023
Daniel Perkins, Kimberley Day, Jerome Sarris et al.
27 citations
Ayahuasca, a psychoactive Amazonian brew containing DMT and harmala alkaloids, is increasingly used worldwide in traditional and neo-shamanic settings. A review of existing literature and original qualitative data from a large cross-sectional study of ayahuasca drinkers proposes a model of five key psychotherapeutic processes inherent to the experience: somatic effects, introspection and emotional processing, increased self-connection, increased spiritual connection, and gaining insights and new perspectives. These processes, facilitated by neurobiological effects, are argued to lead to beneficial mental health and wellbeing outcomes. The model highlights differences from other classic psychedelics and implications for therapeutic use.
Psychoactives
October 3, 2023
Daniel Perkins, Emérita Sátiro Opaleye, José Carlos Bouso et al.
18 citations
Ayahuasca drinkers almost universally report gaining insights during their experiences, and these insights strongly predict subsequent beneficial life and lifestyle changes, including improvements in psychological wellbeing and mental health. In a large international survey of 8,907 ayahuasca drinkers, common changes attributed to ayahuasca included personal, vocational, religious or spiritual, and health-related shifts, along with healthier behaviors. Demographic factors and drinking patterns also predicted these outcomes. The findings suggest that insights and resulting life changes are central to the transformative effects of ayahuasca, occurring across diverse contexts and groups.
International journal of toxicology
January 1, 2024
Eleanor White, Tom Kennedy, Simon Ruffell et al.
13 citations
A systematic thematic review of 78 articles found that ayahuasca and its main psychoactive alkaloid DMT are generally safe in controlled settings, with serious adverse effects rarely reported among healthy populations. However, some adverse human events have been documented. In animal models, higher doses of ayahuasca showed abortifacient and teratogenic effects, and isolated harmala alkaloid studies—especially with harmaline—revealed potential toxicity at higher doses, which may increase when co-administered with certain medications. The authors note that high-dose animal studies using synthetic isolates may not translate to human use of therapeutic plant-based extracts. The review concludes that traditional use of ayahuasca and DMT has an acceptable safety profile, but further randomized controlled trials with larger samples and longer follow-up are needed.
Drug Science Policy and Law
January 1, 2024
Simon Ruffell, Sam Gandy, WaiFung Tsang et al.
10 citations
Participating in ayahuasca retreats in a traditional Indigenous Amazonian context was associated with significant increases in nature relatedness and improvements in depression and stress, but not anxiety. A moderate negative correlation indicated that greater increases in nature relatedness were linked to lower stress levels. The study involved a mean of 6.31 ceremonies. It remains unclear whether changes resulted from the ayahuasca brew, the ceremonies, or the retreat setting. The findings suggest a potential therapeutic role for such retreats as a multidimensional intervention, but further research is needed to identify mediators and assess long-term effects.
Brain and Behavior
July 1, 2025
Megan Calnan, Grace Blest‐hopley, Chris Busch et al.
4 citations
Military veterans who attended psilocybin or ayahuasca retreats showed significant improvements in eight measures of mental health and community reintegration, with the largest gains in depression (29.1% reduction on the PHQ-9) and PTSD (26.1% reduction on the PCL-5). Psilocybin retreats produced greater improvements on seven of eight outcomes, while ayahuasca retreats yielded slightly larger PTSD reductions (26.4% vs. 24.8%). Male participants improved more on all outcomes except PTSD, where females showed a larger reduction (32.1% vs. 24.1%). Veterans with worse initial symptoms benefited most. The findings suggest psychedelic retreats could offer a holistic treatment framework addressing psychological well-being, community factors, and civilian reintegration.
Frontiers in Psychiatry
August 6, 2025
Grace Blest‐hopley, Giuseppe Pasculli, Simon Ruffell et al.
3 citations
Veterans with traumatic brain injuries who participated in psilocybin retreats showed improvements in PTSD, depression, and anxiety symptoms four weeks afterward. PTSD scores decreased by 50%, depression scores by 65%, and anxiety scores by 28%. Electroencephalography measurements revealed decreased delta and theta brainwave power in frontal and temporal regions, along with enhanced coherence in alpha and beta bands, suggesting improved cognitive control, emotional processing, and neural communication. The preliminary findings provide a rationale for larger controlled studies.
February 21, 2023
Simon Ruffell, Nigel Netzband, WaiFung Tsang et al.
3 citations
preprint
Ayahuasca, a psychedelic brew from the Amazon Rainforest made from the Banisteriopsis caapi vine and a DMT-containing plant like Psychotria viridis, has seen a surge in global interest since 2000. This review covers its history, pharmacology, and phenomenological effects, as well as clinical applications. Tourists increasingly travel to the Amazon to consume it, and retreat centers offering plant medicine have become a thriving business. Anecdotal reports range from evangelical accounts to stories of physical and psychological harm. The brew shows promise as a psychedelic agent warranting more empirical research into its neurochemical mechanisms and therapeutic uses.
June 24, 2022
Simon Ruffell, Sam Gandy, WaiFung Tsang et al.
2 citations
preprint
Participation in an indigenous Amazonian ayahuasca retreat, with an average of 5.85 ceremonies attended, was associated with significant increases in nature relatedness and mindfulness, as well as improvements in depression, state anxiety, and trait anxiety. Changes in nature relatedness were negatively correlated with depression, state anxiety, and trait anxiety, and positively correlated with mindfulness. It remains unclear whether these changes resulted from the brew, the ceremony, or the retreat setting. The pilot study suggests a potential therapeutic role for such retreats as a multidimensional intervention, but further research is needed to identify mediators and assess long-term effects.
February 14, 2022
Daniel Perkins, Simon Ruffell, Kimberley Day et al.
1 citation
preprint
Ayahuasca, a psychoactive Amazonian brew containing harmala alkaloids and DMT, is increasingly used globally in traditional and neo-shamanic settings. This paper reviews existing literature and original data from the Global Ayahuasca Project, the largest cross-sectional study of ayahuasca drinkers, to propose a model of psychotherapeutic processes leading to mental health benefits. The model identifies five key processes: somatic effects; introspection and emotional processing; increased self-connection, value, and love; increased spiritual connection; and gaining insights and new perspectives. Differences from other classic psychedelics are noted, and the model aims to improve therapeutic use and optimize clinical treatment models.
Scientific reports
November 20, 2025
Daniel Perkins, Andreas Halman, Anna Urokohara et al.
Acute subjective experiences induced by psychedelics, particularly mystical experiences, are linked to therapeutic benefits such as reduced depression, anxiety, and addiction. This study assessed a purified encapsulated DMT-harmala alkaloid product in 17 dosing sessions with 9 healthy volunteers. Strong positive correlations were found between total dose and scores on mystical experience questionnaires (MEQ-30 and SIME). The formulation reliably produced intense subjective experiences, exceeding those reported in most naturalistic ayahuasca studies, and these experiences were robustly associated with beneficial persisting psychological effects. The findings suggest this formulation warrants further clinical trials to evaluate its therapeutic potential and safety.
Drug Science Policy and Law
January 1, 2023
WaiFung Tsang, Simon Ruffell, Nigel Netzband et al.
Adults who attended ayahuasca retreats in Peru reported fewer symptoms of inattention, hyperactivity, and impulsivity afterward, regardless of retreat length or number of ceremonies. In an exploratory pilot study, 49 adults completed the Adult ADHD Self-Report Scale before and after retreats lasting 8 days to 4 weeks. Scores for inattention, hyperactivity/impulsivity, and total symptoms all dropped significantly. Only four participants had a prior ADHD diagnosis. The findings suggest ayahuasca may be associated with reductions in core ADHD features, but controlled trials are needed to confirm causality.