BACKGROUND: Ketamine is an effective rapid-acting treatment for treatment-resistant depression (TRD), producing antidepressant effects within hours of administration. Because it induces states of heightened neuroplasticity and psychological openness, psychotherapy may enhance its therapeutic effects. METHODS: This exploratory, nonrandomized, open-label clinical trial evaluated the adjunctive...
NeuropharmacologyJuly 1, 2026Anne Nathalia De Sousa-Silva, Clarissa de Almeida Moura, Carina Ioná De Oliveira Torres et al.1 citation
N,N-dimethyltryptamine (DMT) is an naturally occurring indoleamine with hallucinogenic and antidepressant effects in humans. Here, we compared the effects of DMT and S-ketamine, a fast-acting antidepressant, in helpless mice. To induce helplessness, male single and group-housed mice were exposed to inescapable footshock stress; only helpless animals were subsequently treated with S-ketamine 10...
Background Ketamine has emerged as an effective rapid-acting treatment for treatment-resistant depression (TRD), producing significant antidepressant effects within hours of administration. Given ketamine’s capacity to induce states of heightened neuroplasticity and psychological openness, psychotherapy may represent a meaningful complement to its pharmacological effects — facilitating...
Abstract Paradoxically, psychedelics have long been used as models of both psychosis and therapy. After proposing mystical experiences as a link between these models for lysergic acid diethylamide (LSD), we aimed to extend and refine this framework for N,N -Dimethyltryptamine (DMT). In a randomised, placebo-controlled, double-blind, crossover study, 25 healthy participants received DMT (60mg)...
The use of psychedelics in the treatment of psychopathologies has been expanding, highlighting Psychedelic-Assisted Psychotherapy (PAP) as a promising resource in mental health care. This systematic review investigates. This systematic review investigates whether and how cognitive-behavioral therapies are integrated with psychedelic substances—both classical and atypical—for the treatment of...
Acute subjective experiences induced by psychedelics have been identified as important mediators of therapeutic outcomes in many studies. Mystical experiences specifically, have been correlated with a range of therapeutic outcomes including reductions in symptoms of depression, anxiety and addiction. This paper assesses acute subjective experiences induced by an encapsulated DMT-harmala...
Vaporized N,N-Dimethyltryptamine (DMT) has a short duration and simple application, prompting this technique as a new approach for psychedelics' clinical use. Building on our initial dose-ascending studies and addressing potential confounding effects of dosing order, this study is the first to evaluate inhaled DMT in a randomized, placebo-controlled, double-blind design. Given DMT's therapeutic...
Depression affects over 185 million people worldwide, with approximately one-third classified as treatment-resistant depression (TRD). Current treatments, such as oral antidepressants, often take around 3 weeks to become effective, with no immediate anti-suicidal benefits. The field urgently needs innovative therapies that provide rapid relief. Psychedelics like psilocybin and ayahuasca have...
Research SquareMarch 5, 2025Expedito Do Nascimento Júnior, Luiz Pereira, Wigínio Lira-Bandeira et al.
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Abstract Depression remains a debilitating mental health disorder affecting millions worldwide, with growing prevalence among adolescents. Recent studies highlight the critical role of the somatosensory cortex in the neuropathology of depression, including structural alterations that impair cortical function. This study investigates the prophylactic effects of ayahuasca, a traditional...
N,N-Dimethyltryptamine (DMT), a naturally occurring psychedelic tryptamine contained in the indigenous ayahuasca brew, has shown antidepressant effects. This open-label clinical trial investigates for the first time the efficacy of vaporized DMT in treatment-resistant depression (TRD). Six TRD patients participated in an open-label, fixed-order, dose-escalation study, receiving a lower (15 mg)...
Serotonergic psychedelics have potential therapeutic effects in treating anxiety and mood disorders, often after a single dose, and are suggested to have plasticity-inducing action. However, a comprehensive mechanism of action is still lacking. Here, we investigated how a single dose of the short-acting 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) acts on gene expression from microdissected...
Emerging evidence indicates that ayahuasca consumption may have beneficial mental health effects. This study undertakes the largest analysis to date of associations between naturalistic ayahuasca use and current mental health status via an online cross-sectional survey. The sample included 7,576 participants (average age 41, 47% female) who had consumed ayahuasca in religious, traditional, or...
Psychedelics are being increasingly examined for their therapeutic potential in mood disorders. While the acute effects of ayahuasca, psilocybin, and lysergic acid diethylamide (LSD) last over several hours, inhaled N,N-Dimethyltryptamine (DMT) effects last around 10 min, which might provide a cost- and time-effective alternative to the clinical application of oral psychedelics. We aimed at...
Abstract Psychedelics are a unique class of drug that commonly produce vivid hallucinations as well as profound psychological and mystical experiences. A grouping of interconnected brain regions characterized by increased temporal coherence at rest have been termed the Default Mode Network (DMN). The DMN has been the focus of numerous studies assessing its role in self-referencing, mind...