Experimental neurology • September 1, 2026 • Javier Calleja-Conde, Víctor Echeverry-Alzate, Marina Sanz-sancristobal et al.
In a preclinical model of Parkinson's disease, the compound N,N-dimethyltryptamine (DMT), the main psychoactive ingredient in ayahuasca, reduced neuroinflammation and preserved neurons in the nigrostriatal pathway. Treated animals also showed improvements in behavior. These results suggest DMT may have disease-modifying potential for Parkinson's disease, a progressive neurodegenerative disorder marked by loss of dopaminergic neurons and chronic inflammation, for which current treatments only relieve symptoms.
Clinical pharmacology and therapeutics • July 1, 2026 • Tijana Stojanović, Kent W Nilsson, Robert Fredriksson et al.
The clinical trial landscape for ayahuasca and DMT expanded rapidly after 2020-2021, dominated by early-stage development. Most trials are phase I, primarily sponsored by academic or hospital institutions, and focus on DMT-only administration. Eligibility criteria are conservative, enrolling medically and psychiatrically healthy adults with extensive cardiovascular and psychiatric exclusions. Primary outcomes prioritize acute safety, physiological monitoring, and characterization of subjective altered-states, while disorder-specific symptom endpoints are less common. Publications from depression-focused trials provide preliminary evidence of potential clinical effects, but the field remains constrained by a limited number of indication-specific programs beyond depression.
Neuropsychiatrie : Klinik, Diagnostik, Therapie und Rehabilitation : Organ der Gesellschaft Osterreichischer Nervenarzte und Psychiater • June 30, 2026 • Cielo A Estela-fernandez, Reem Mohamed Yousif Elsheikh, Dal Bianco Beatrice et al.
Psychedelics show significant potential for treatment-resistant depression (TRD) by promoting neuroplasticity, corticolimbic function, and epigenetic changes beyond serotonergic agonism. Psilocybin-assisted therapy induces short-term symptom improvement lasting weeks to months. Ketamine, in intravenous, subcutaneous, and oral forms, produces rapid and robust reductions in depressive symptoms and relapses without impairing cognitive function. Esketamine yields early, clinically meaningful improvements in function and productivity. Ayahuasca demonstrates fast and sustained effects with higher remission rates and good safety. Despite encouraging findings, large, well-designed studies are needed before psychedelics become standard recommendations for TRD.
June 21, 2026 • Jonathan David, Aviva Berkovich‐ohana, Yair Dor‐ziderman et al.
preprint
Ayahuasca use among ultra-Orthodox (Haredi) Jews is adapted to Jewish contexts, with ceremonies modified to fit religious norms. Motivations for use are primarily therapeutic. Acute experiences include Jewish and Jewish mystical visionary content. Longer-term effects include strengthened belief, connection to Judaism, and changes in religious practice. Religious tensions arise from ayahuasca's perceived foreignness, concerns about idolatry, mixed-gender participation, and competing authority structures. Strategies to address these tensions include medicalization, making the set, setting, and experience religiously permissible ("koshering"), and framing ceremonies as liminal spaces. The findings highlight psychedelics' contextual flexibility and diffusion into understudied populations.
June 19, 2026 • Jules Evans, Christian Jurlando, David Luke et al.
preprint
Belief in sorcery and supernatural harm is common among Western psychedelic users, with many reporting experiences they interpret as shamanic attack. In a survey of 895 adults involved in psychedelic culture, participants often downplayed indigenous sorcery frameworks in favor of psychological explanations, yet some left ceremonies convinced they had been harmed supernaturally. The study estimates the prevalence of such beliefs, examines how psychedelic experiences and cultural immersion shift these beliefs, and characterizes experiences interpreted as black magic. It also assesses whether fear of magical retaliation inhibits criticism of ceremonial leaders. Findings aim to inform harm reduction in ceremonial settings.
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.
PLoS ONE • April 23, 2019 • Roland R. Griffiths, Ethan Hurwitz, Alan K. Davis et al. • 249 citations
Experiences interpreted as personal encounters with God, whether occurring naturally or after taking psychedelic drugs, share striking similarities. In an online survey of over 4,200 people, those who had a nondrug encounter most often called it God, whereas those who had a psychedelic encounter most often called it Ultimate Reality. Regardless of origin, most participants vividly remembered the encounter as involving a conscious, benevolent, intelligent, sacred, eternal, and all-knowing presence. About half of all encounters met criteria for a complete mystical experience. More than two-thirds of self-identified atheists no longer identified as atheist afterward.
Psychological Medicine • June 15, 2018 • Fernanda Palhano-Fontes, Dayanna Barreto, Heloisa Onias et al. • 827 citations
A single dose of ayahuasca reduced depression severity more than placebo in patients with treatment-resistant depression. Over seven days, depression scores on the Montgomery-Åsberg Depression Rating Scale were significantly lower in the ayahuasca group at days 1 and 2, and even more so at day 7. Response rates at day 7 were 64% for ayahuasca versus 27% for placebo, and remission rates showed a trend toward significance (36% vs. 7%). Effect sizes grew from day 1 to day 7, indicating sustained improvement. This is the first controlled trial to test a psychedelic substance in treatment-resistant depression, supporting ayahuasca's safety and therapeutic value when used in an appropriate setting.
Therapeutic Advances in Psychopharmacology • March 18, 2016 • Rafael G. Dos Santos, Flávia de Lima Osório, José Alexandre S. Crippa et al. • 306 citations
A systematic review of clinical trials from 1990 to 2015 examined the therapeutic potential of ayahuasca, psilocybin, and LSD for mood and anxiety disorders and drug dependence. Six trials met inclusion criteria. The reviewed studies suggest beneficial effects for treatment-resistant depression, anxiety and depression associated with life-threatening diseases, and tobacco and alcohol dependence. All drugs were well tolerated. However, all studies had small sample sizes, and half were open-label, proof-of-concept studies. The authors conclude these substances may be useful pharmacological tools, but randomized, double-blind, placebo-controlled studies with more patients are needed to replicate preliminary findings.
Front Pharmacol • March 2, 2016 • 237 citations
Ayahuasca, an Amazonian psychoactive brew, is gaining scientific attention for potential therapeutic benefits. Its psychotherapeutic potential is largely based on strong serotonergic effects, while the sigma-1 receptor agonist effect of its active ingredient dimethyltryptamine may explain its diverse traditional uses. In appropriate therapeutic or ritual settings, with proper preparation and integration, ayahuasca has proven effective in treating substance dependence. The article emphasizes two key points: therapeutic effects are best understood through a bio-psycho-socio-spiritual model, and biologically, ayahuasca may counteract chronic low-grade inflammation and oxidative stress via the sigma-1 receptor, accounting for its wide-ranging therapeutic indications.
Journal of Clinical Psychopharmacology • December 11, 2015 • Rafael Faria Sanches, Flávia de Lima Osório, Rafael G. Dos Santos et al. • 468 citations
A single oral dose of ayahuasca, an Amazonian brew containing dimethyltryptamine and harmine, produced fast-acting and sustained reductions in depression severity among 17 patients with recurrent depression. Scores on the Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, and Brief Psychiatric Rating Scale decreased significantly from 80 minutes through 21 days after intake. Brain imaging showed increased blood flow in the left nucleus accumbens, right insula, and left subgenual area—regions involved in mood regulation. Vomiting occurred in 47% of participants, but no other adverse effects were reported. The authors suggest ayahuasca may have antidepressant properties but call for replication in randomized, double-blind, placebo-controlled trials.
Brazilian Journal of Psychiatry • March 1, 2015 • Flávia de Lima Osório, Rafael Faria Sanches, Ligia Ribeiro Horta de Macedo et al. • 486 citations
A single dose of ayahuasca produces fast-acting reductions in anxiety and depression symptoms in people diagnosed with a depressive disorder.
PLoS ONE • February 18, 2015 • Fernanda Palhano-Fontes, Kátia C. Andrade, Luís Fernando Tófoli et al. • 461 citations
Ayahuasca, a psychedelic brew used traditionally by Amazonian Amerindians, significantly reduces activity in key hubs of the Default Mode Network (DMN), specifically the Posterior Cingulate Cortex (PCC)/Precuneus and medial Prefrontal Cortex (mPFC), as measured by fMRI in ten experienced subjects. Functional connectivity within the PCC/Precuneus also decreased after intake, while the orthogonality between the DMN and task-positive network showed no significant change. These findings suggest that the altered state of consciousness induced by Ayahuasca, similar to effects from psilocybin, meditation, and sleep, involves modulation of DMN activity and connectivity.
Current Drug Abuse Reviews • June 1, 2013 • Gerald Thomas, Philippe Lucas, N. Rielle Capler et al. • 327 citations
Ayahuasca-assisted therapy was linked to meaningful improvements in factors related to problematic substance use among a rural aboriginal population. The observed changes suggest positive psychological and behavioral shifts, indicating that this therapeutic approach merits further, more rigorous investigation.
PLoS ONE • August 8, 2012 • José Carlos Bouso, Débora González, Sabela Fondevila et al. • 313 citations
Regular ayahuasca use over one year is associated with better psychological well-being, mental health, and cognitive performance compared to active controls in non-ayahuasca religions. Users scored higher on Reward Dependence and Self-Transcendence, lower on Harm Avoidance and Self-Directedness, and showed significantly lower psychopathology scores. They performed better on tests of attention, executive function, and working memory (Stroop test, Wisconsin Card Sorting Test, Letter-Number Sequencing). Life attitude measures indicated greater spiritual orientation, purpose in life, and psychosocial well-being. No evidence of psychological maladjustment, mental health deterioration, or cognitive impairment emerged in the ayahuasca group.
Human Brain Mapping • September 16, 2011 • Dráulio Barros de Araújo, Sidarta Ribeiro, Guillermo Cecchi et al. • 241 citations
Ayahuasca, a hallucinogenic brew containing serotonergic agonists and reuptake inhibitors, triggers vivid visual imagery during ceremonies. Using functional magnetic resonance imaging while participants performed a closed-eyes imagery task, the brew produced a robust increase in activation across occipital, temporal, and frontal brain areas. In the primary visual area, activation levels matched those of natural image viewing with eyes open. This effect correlated with individual perceptual changes measured by psychiatric scales. Activity in areas BA30 and BA37, linked to episodic memory and contextual associations, was also potentiated. Modulation of BA10, involved in prospective imagination and working memory, was detected. The findings suggest Ayahuasca seeings arise from an extensive network for vision, memory, and intention, lending a sense of reality to inner experiences.
Addiction • December 20, 2006 • Robert S. Gable • 240 citations
A systematic review and interviews with ceremony participants assessed the acute toxicity and psychological risks of ayahuasca, a brew containing dimethyltryptamine (DMT) and β‐carbolines used in religious ceremonies. No animal models tested ayahuasca's acute toxicity or abuse potential, but separate studies of DMT and harmala alkaloids suggest a lethal human dose is probably over 20 times a typical ceremonial dose. Adverse effects may occur with casual use, especially alongside serotonergic substances. DMT can cause aversive reactions or transient psychotic episodes that resolve within hours. There is no evidence of substantial abuse potential, and long-term psychological benefits are documented when used in a well-established social context. The safety margin is comparable to codeine, mescaline, or methadone.
The Journal of Nervous and Mental Disease • February 1, 1996 • Charles S. Grob, Dennis J. Mckenna, J. C. Callaway et al. • 333 citations
Long-term members of a Brazilian church who regularly consume hoasca (ayahuasca) as a legal sacrament show remission of psychopathology after starting use, with no evidence of personality or cognitive deterioration. Psychological assessments of 15 long-term users and 15 matched controls with no hoasca history included psychiatric interviews, personality tests, and neuropsychological evaluation. Users reported high functional status. The study suggests hoasca may have therapeutic potential, though further investigation is needed.