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.
Braz J Psychiatry • July 7, 2026
The article argues that while ayahuasca has shown promise in early depression research, the field must move beyond initial enthusiasm to address methodological challenges and ethical considerations. It calls for rigorous, well-controlled studies to determine efficacy and safety, and emphasizes the need to understand the specific mechanisms of action. The authors suggest that future research should focus on long-term outcomes, potential risks, and the integration of ayahuasca into broader therapeutic contexts, rather than simply celebrating its potential.
July 5, 2026 • Mark Groeneveld
preprint
A practical manual for solo and guided MDMA therapy, grounded in a mechanistic framework of memory reconsolidation, predictive processing, complex system dynamics, and the defense cascade model, explains how MDMA therapy can durably improve mental illnesses by enabling the unlearning of inaccurate mental models. It provides evidence-based guidance on safety, session preparation, troubleshooting, and long-term healing, extending beyond clinical illness to address mental models that hinder community relationships, cognitive flexibility, and ethical reasoning. The manual emphasizes scientific rigor, transparency, and respect for autonomy, and includes discussion of tradeoffs between practitioner- and self-guidance.
Neuroscience and biobehavioral reviews • July 1, 2026 • Athanasia Kontouli, Michael J Hove, Alexandre Lehmann et al.
Trance states induced by music, from shamanic rituals to electronic dance music raves, share common musical features and cultural narratives. Anthropological and neuroscientific evidence suggests that different forms of trance engage partially overlapping neural dynamics, including increased low-frequency brain wave synchronization and a shift from executive control networks to limbic and default mode networks. These patterns reflect the interplay of cognitive, emotional, and sensory systems, though current empirical evidence remains fragmented and methodologically heterogeneous. The review emphasizes trance as both a cultural and biological phenomenon and calls for integrating phenomenological and neurophysiological data to build comprehensive models of music-induced non-ordinary states of consciousness.
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.
Zenodo (CERN European Organization for Nuclear Research) • July 1, 2026 • Schüller Thomas
DMT is the fourth classical psychedelic in a series and has five distinguishing features: oral inactivity without an MAO inhibitor; ultra-short duration (minutes) when smoked or injected; ayahuasca as a plant combination (DMT source plus β-carboline MAOI); endogenous occurrence in mammals; and the unique religious legal ruling Gonzales v. O Centro (2006). Chemically, DMT is a tryptamine (like psilocybin and LSD), contrasting with the phenethylamine mescaline. This bilingual full work provides a transdisciplinary scientific overview of DMT and ayahuasca across eight disciplines, with explicit labeling of levels of certainty (confirmed / probable / open).
June 23, 2026 • Carlos Minuano
Benki Piyãko, an Ashaninka leader in the Brazilian state of Acre, warns that the Amazon rainforest, which he calls one of the world's largest pharmacies, is being destroyed. This statement highlights multiple threats to the Amazon and underscores a growing debate about ayahuasca, an Indigenous psychedelic beverage considered a forest medicine.
Interações - cultura e comunidade • June 23, 2026 • Leonardo Tondato Mello, Kemily Bakri Ottoni, Janaína Liz Aquino
The global expansion of ayahuasca carries both creative and destructive potential for mental health, depending on the historical and social context of Indigenous peoples' exclusion and marginalization since the colonial period. Ongoing studies of ayahuasca's therapeutic effects indicate that proper management and interdisciplinary collaboration between ancestral knowledge and Western psychology/psychiatry are essential. The article concludes that a fair and respectful exchange with Indigenous knowledge is necessary to avoid predatory appropriation.
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.
Progress in neuro-psychopharmacology & biological psychiatry • June 20, 2026 • Ewen Kervadec, Pauline Mathieu, Baptiste Fauvel et al.
A French translation of the Altered States of Consciousness (5D-ASC) questionnaire was psychometrically validated using data from 777 participants who recalled a past naturalistic psychedelic experience. The 11-subscale structure showed better fit than higher-order models, though fit indices fell slightly below conventional thresholds. Internal consistency was excellent for global scores (α = 0.95) and satisfactory across subscales (α = 0.63–0.84). Measurement invariance across substance categories was confirmed, with latent factor differences aligning with known pharmacological profiles. The findings provide preliminary evidence supporting the French 5D-ASC's validity, enabling francophone research linking subjective experience to therapeutic outcomes.
ACS Pharmacol Transl Sci • December 10, 2020 • 534 citations
Classic psychedelics induce altered states of consciousness that people often find meaningful. In human studies, when the overall intensity of drug effects is statistically controlled, specific subjective experiences—not just neurobiological changes—predict therapeutic and other positive outcomes. The authors argue that these subjective effects are necessary for lasting benefits and account for most of the improvement, while underlying brain mechanisms are likely necessary but insufficient on their own.
eLife • October 25, 2018 • Katrin H. Preller, Joshua B. Burt, Jie Lisa Ji et al. • 416 citations
Lysergic acid diethylamide (LSD) reduces associative brain connectivity while increasing sensory-somatomotor and thalamic connectivity. These neural effects, along with the subjective experience, are fully blocked by ketanserin, a selective 5-HT2A receptor antagonist. The spatial pattern of LSD's effects across the brain matches the distribution of 5-HT2A receptor gene expression in humans. These results strongly implicate the 5-HT2A receptor in LSD's neuropharmacology, informing the neurobiology of psychedelics and guiding development of psychedelic-based therapeutics.
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.
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 31, 2010 • Erich Studerus, Alex Gamma, Franz X. Vollenweider • 693 citations
The original OAV scales measured multidimensional constructs. Eleven new lower-order scales were developed and showed good psychometric properties. These new scales are probably better for assessing altered states of consciousness caused by drugs.
Annals of the New York Academy of Sciences • May 1, 2008 • 396 citations
Spontaneous brain activity, measured during rest, has been proposed as a way to understand brain-behavior relationships, but its value is debated. This review argues that altered states of consciousness—such as sleep, anesthesia, coma, vegetative state, epileptic loss of consciousness, and somnambulism—offer a privileged way to study these links. Early PET studies showed that extremely low or high brain activity often accompanies unconsciousness, but this link is not absolute. Voxel-based analyses consistently found impaired associative frontoparieto-cingulate areas across altered states. Recent fMRI studies reveal structured slow neuronal oscillations and coherent BOLD patterns, especially in the default-mode network, even during unconsciousness. These patterns may reflect default brain connectivity that transcends consciousness, but their functional significance remains unclear.
Annals of Behavioral Medicine • November 15, 2006 • 357 citations
A body scan meditation, a component of Mindfulness-Based Stress Reduction, produces distinct immediate physiological effects compared to other relaxing activities. In two laboratory studies, healthy young adults showed greater increases in respiratory sinus arrhythmia (a measure of cardiac parasympathetic activity) during meditation than during progressive muscular relaxation or listening to a novel. Meditation also shortened the cardiac pre-ejection period, indicating increased sympathetic activity. These opposing autonomic changes may explain why heart rate did not change. Women experienced a larger drop in diastolic blood pressure during meditation, while men showed a greater increase in cardiac output. The findings suggest that body scan meditation triggers a unique combination of parasympathetic and sympathetic responses.
Psychological Bulletin • January 1, 2005 • Dieter Vaitl, Niels Birbaumer, John Gruzelier et al. • 446 citations
Altered states of consciousness (ASC) can occur spontaneously, be evoked by physical or physiological stimulation, induced by psychological means, or caused by diseases. Psychological and neurobiological approaches reveal four dimensions characterizing ASC: activation, awareness span, self-awareness, and sensory dynamics. Neurophysiologically, different states of consciousness arise from compromised brain structure, transient changes in brain dynamics (disconnectivity), and neurochemical and metabolic processes. Environmental stimuli, mental practices, and self-control techniques can also temporarily alter brain functioning and conscious experience.
Journal of Pharmacology and Experimental Therapeutics • July 1, 1999 • M. Mas, M. Farré, R. de la Torre et al. • 362 citations
In a double-blind, randomized, crossover trial, eight men with prior recreational MDMA use received single oral doses of 125 mg or 75 mg of MDMA, 40 mg of amphetamine, or placebo. Both MDMA doses significantly raised systolic blood pressure by 40 mm Hg and heart rate by 30 beats/min, and dilated pupils, compared with placebo. Oral temperature did not change significantly. Plasma cortisol increased after MDMA; prolactin only rose after the higher dose. MDMA elimination half-lives were 8.6 hours (high dose) and 7.7 hours (low dose). The cardiovascular effects at rest suggest potential toxicity in real-world settings with crowding or physical exertion.
Pharmacopsychiatry • July 1, 1998 • 597 citations
Altered states of consciousness (ASCs) share three core dimensions regardless of how they are induced: Oceanic Boundlessness, Dread of Ego Dissolution, and Visionary Restructuralization. This was shown through 11 experiments with 393 healthy subjects and a field study with 1,133 participants across six countries. The APZ questionnaire, developed to measure these dimensions, shows satisfactory reliability and validity and has become an international standard. A psychometrically improved German version exists, along with the BETA questionnaire for additional dimensions. Versions are available in several languages, with some still untested.
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.