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.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
May 1, 2025
Marcelo Falchi-Carvalho, Fernanda Palhano-Fontes, Isabel Wießner et al.
35 citations
Vaporized DMT, a short-acting psychedelic, rapidly reduced depression symptoms in patients with treatment-resistant depression. In an open-label trial, 14 patients received inhaled DMT at 15 mg and then 60 mg. The treatment was safe and well-tolerated, with no serious adverse events. By day 7, depression scores on the Montgomery-Asberg Depression Rating Scale dropped by an average of 21.14 points. The response rate was 85.71%, and the remission rate was 57.14%, with effects lasting up to 3 months. Suicidal ideation also decreased significantly, with no severe ideation the day after dosing. Vaporized DMT offers a non-invasive, time-efficient alternative to longer-acting psychedelics and traditional antidepressants.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
March 1, 2024
Marcelo Falchi-Carvalho, Isabel Wießner, Sérgio Ruschi B Silva et al.
25 citations
Inhaled N,N-Dimethyltryptamine (DMT) produces dose-dependent increases in the intensity, positive valence, and perceptual effects of subjective experiences, with only mild, transient, and self-limited increases in blood pressure and heart rate. No changes in safety blood biomarkers or serious adverse events occurred. The acute effects last around 10 minutes, offering a potentially cost- and time-effective alternative to longer-acting oral psychedelics for clinical use in mood disorders. This open-label, single-ascending, fixed-order, dose-response study in 27 healthy volunteers tested five dose pairs (5/20 mg through 15/60 mg) of inhaled DMT (BMND01 candidate).
Molecular Psychiatry
January 1, 2025
Margareth Nogueira, Daiane C Ferreira Golbert, Richardson Menezes et al.
18 citations
A single dose of the short-acting psychedelic 5-MeO-DMT alters expression of genes related to plasticity and neuronal activity in specific brain regions of mice, including the anterior cingulate cortex, basolateral amygdala, and ventral hippocampus. Immediate early genes Arc and Zif268 changed within hours, while TRIP8b, a modulator of neuronal activity, increased in the ventral hippocampus after five days. Behaviorally, 5-MeO-DMT produced mixed anxiety-reducing and anxiety-increasing effects in standard tests, but mice pre-treated with the compound and then exposed to acute stress showed lower corticosterone levels and strong anxiety-reducing effects. The findings suggest molecular pathways through which 5-MeO-DMT may produce anxiolytic effects.
Psychedelic medicine (New Rochelle, N.Y.)
March 1, 2025
Marcelo Falchi-Carvalho, Handersson Barros, Raynara Bolcont et al.
16 citations
Vaporized N,N-dimethyltryptamine (DMT) produced rapid and sustained antidepressant effects in a small open-label trial of six people with treatment-resistant depression. Depression severity, measured by the Montgomery-Asberg depression rating scale (MADRS) and Patient Health Questionnaire-9 (PHQ-9), decreased significantly from the first day through one month after dosing. The average MADRS score dropped by 22 points at day 7 and 17 points at one month. By day 7, 83.33% of patients responded to treatment and 66.67% achieved remission; at one month, 66.67% maintained response and 50% maintained remission. The short-acting, noninvasive vaporized route may improve accessibility to psychedelic treatments.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
June 17, 2025
Isabel Wießner, Marcelo Falchi-Carvalho, Sophie Laborde et al.
7 citations
Inhaled vaporized DMT (60 mg) produces profound altered states of consciousness and is safe and well-tolerated in healthy adults. In a randomized, double-blind, placebo-controlled crossover trial with 25 participants, DMT significantly increased subjective intensity and most measures on the 5D-ASC, HRS, and MEQ questionnaires compared to an active placebo (0.6 mg DMT). Physiological parameters such as blood pressure and heart rate rose transiently within safe limits. Adverse events were predominantly mild and temporary. Biochemical changes were not clinically relevant. Physiological increases correlated with subjective experiences, suggesting a link between bodily responses and the psychedelic state.
Journal of Psychoactive Drugs
November 23, 2024
Daniel Perkins, Jerome Sarris, Tessa Cowley-Court et al.
5 citations
People who consume ayahuasca in naturalistic settings—religious, traditional, or non-traditional—report better current mental health and greater psychological well-being, according to a large online survey of 7,576 participants from over 50 countries. More lifetime ayahuasca uses were linked to better mental health scores, and this association remained strong even after accounting for other factors and did not fade over time. Strong mystical experiences, self-insights, and community or social support were also tied to better mental health and well-being, whereas acute extreme fear during sessions and difficulty integrating the experience were linked to poorer outcomes. These patterns held for individuals both with and without a history of mental illness.
Neuropharmacology
July 1, 2026
Anne Nathalia De Sousa-Silva, Clarissa de Almeida Moura, Carina Ioná De Oliveira Torres et al.
1 citation
In helpless mice, the psychedelic compound N,N-dimethyltryptamine (DMT) produced rapid and long-lasting antidepressant effects comparable to the fast-acting antidepressant S-ketamine. DMT at 10 mg/kg reversed escape deficits and reduced immobility in several behavioral tests, with effects lasting up to 8 days, whereas S-ketamine's effects lasted up to 30 hours. DMT also showed anxiolytic-like effects, reversing stress-induced hypolocomotion and increasing open-arm exploration, while S-ketamine did not. Neither drug altered behavior in the novelty-suppressed feeding test. These findings suggest DMT has transdiagnostic therapeutic potential for stress-related disorders.
European Archives of Psychiatry and Clinical Neuroscience
March 28, 2026
Yves Martins Varela, Vagner Deuel O de Tavares, Luiza Macedo Delgado et al.
1 citation
Cognitive-behavioral therapies are being combined with psychedelic substances such as ketamine, psilocybin, and MDMA to treat mental disorders, but the way they are integrated varies widely across studies. A systematic review of 9 clinical trials involving 283 patients found that traditional cognitive behavioral therapy was the most common approach, used in 6 studies, while mindfulness-based cognitive therapy and acceptance and commitment therapy were each used in 2 and 1 studies respectively. The timing of therapy relative to the psychedelic experience—before, during, or after—also differed. The findings highlight the need for more consistent research to clarify how these therapeutic models are best implemented.
medRxiv Preprint Server
May 31, 2026
Yves Martins Varela, Patrícia Cavalcanti-Ribeiro, Geovan Menezes de Sousa et al.
preprint
Ketamine rapidly reduces depression symptoms in treatment-resistant depression, but its effects may be enhanced by combining it with psychotherapy. The drug induces neuroplasticity and psychological openness, which could help patients process emotions, restructure thoughts, and maintain improvements. However, research has not yet thoroughly examined whether adding structured psychotherapy to ketamine treatment provides additional benefits.
Research Square
May 20, 2026
Isabel Wießner, Marcelo Falchi-Carvalho, Sophie Laborde et al.
The paper explores the relationships among DMT-induced experiences, psychosis, healing, mystical experiences, and positive emotionality. It examines how DMT can serve as a model for psychosis and as a therapeutic tool, while also considering the overlap between these models and mystical experiences. The authors discuss the potential for DMT to induce states resembling psychosis but also to facilitate healing and positive emotional outcomes, suggesting that the context and set and setting are crucial in determining whether the experience leads to distress or well-being.
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.
Research Square
March 5, 2025
Expedito Do Nascimento Júnior, Luiz Pereira, Wigínio Lira-Bandeira et al.
Chronic stress during adolescence can shrink neurons in the brain's somatosensory cortex, a region involved in depression. In a study of juvenile monkeys, those isolated to induce chronic stress had significantly smaller neurons than those living in a family group. However, monkeys given the traditional psychoactive brew ayahuasca before and during isolation had neuron volumes similar to the family group, suggesting the brew may protect against stress-induced cortical atrophy. Trends also hinted at preserved cortical structure in the ayahuasca-treated group, though differences in neuron density and overall cortical volume were not statistically confirmed. The findings point to ayahuasca's potential to mitigate stress-related brain changes and support further research into its therapeutic use for adolescent depression.