BACKGROUND: -dimethyltryptamine (DMT); however, long-term effects, including broader well-being dimensions, are sparsely explored across populations. AIMS: Investigating whether DMT produces sustained improvements in anxiety, life satisfaction, and quality of life, in both healthy individuals and patients with treatment-resistant depression (TRD). METHODS: In 2 open-label clinical trials, 27...
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)...
Background: Psychedelics induce profound changes in perception and thinking; however, little is known about the neural mechanisms and prediction of these effects. Aims: Investigating ayahuasca-induced experiences, mind-wandering, and electroencephalogram (EEG) oscillations, beyond the prediction of subjective experiences by baseline EEG. Methods: In a randomised, double-blind,...
This study aimed to validate and culturally adapt the Altered States of Consciousness Rating Scale (OAV) and Five Dimensional-Altered States of Consciousness Questionnaire (5D-ASC) for Brazilian Portuguese to measure altered states of consciousness in the context of psychedelic research. A parallel back-translation model was employed with expert reviews to ensure linguistic and cultural...
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...
Mindfulness improves mental health and clinical conditions including psychosis and modulates attentional processes including salience-the automatic direction of attention to prominent elements. Aberrant salience-the exaggerated significance attribution to perceived elements-is associated with psychotic experiences, but its interactions with mindfulness remain unexplored. This...
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)...
Psychedelic experiences, especially those induced by substances such as N,N-Dimethyltryptamine (DMT), are often characterized by high subjective intensity, complex visual content, and notable ineffability-that is, the difficulty of being fully expressed in words. This expressive limitation poses a significant challenge to the integration of the experience, which is essential for the therapeutic...
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 Introduction N,N-Dimethyltryptamine (DMT), a naturally occurring psychedelic tryptamine contained in the indigenous ayahuasca brew has shown antidepressant effects. This Phase 2a clinical trial investigates for the first time the efficacy of isolated DMT in treatment-resistant depression (TRD). Methods Six TRD patients participated in an open-label, fixed-order, dose-escalation study,...
Recent studies have begun to understand sleep not only as a whole-brain process but also as a complex local phenomenon controlled by specific neurotransmitters that act in different neural networks, which is called "local sleep". Moreover, the basic states of human consciousness-wakefulness, sleep onset (N1), light sleep (N2), deep sleep (N3), and rapid eye movement (REM) sleep-can concurrently...
For a century, psychedelics have been investigated as models of psychosis for demonstrating phenomenological similarities with psychotic experiences and as therapeutic models for treating depression, anxiety, and substance use disorders. This study sought to explore this paradoxical relationship connecting key parameters of the psychotic experience, psychotherapy, and psychedelic experience. In...
Language has been explored as a window into the mind. Psychedelics, known to affect perception and cognition, seem to change language, but a systematic, time-dependent exploration is lacking. Therefore, we aimed at mapping the psychedelic effects on language over the time course of the acute and sub-acute effects in an explorative manner. For this, 24 healthy volunteers (age [mean±SD, range]:...
The therapeutic potential of the psychedelic brew ayahuasca has been investigated in preclinical and clinical studies. Currently, the most consistent evidence refers to depression. However, various studies suggest that ayahuasca may comprise therapeutic benefits in other health conditions. This narrative review provides a comprehensive, up-to-date overview of ayahuasca's therapeutic effects in...
The therapeutic use of classical psychedelic substances such as d-lysergic acid diethylamide (LSD) surged in recent years. Studies in rodents suggest that these effects are produced by increased neural plasticity, including stimulation of the mTOR pathway, a key regulator of metabolism, plasticity, and aging. Could psychedelic-induced neural plasticity be harnessed to enhance cognition? Here we...
Stream of thought describes the nature of the mind when it is freely roaming, a mental state that is continuous and highly dynamic as in mind-wandering or free association. Classic serotonergic psychedelics are known to profoundly impact perception, cognition and language, yet their influence on the stream of thought remains largely unexplored. To elucidate the effects of LSD on the stream of...
Psychedelics acutely impair cognitive functions, but these impairments decline with growing experiences with psychedelics and microdoses may even exert opposing effects. Given the recent evidence that psychedelics induce neuroplasticity, this explorative study aimed at investigating the potential of psychedelics to sub-acutely change cognition. For this, we applied a randomized, double-blind,...
Background: Controversy surrounds psychedelics and their potential to boost creativity. To date, psychedelic studies lack a uniform conceptualization of creativity and methodologically rigorous designs. Aims: This study aimed at addressing previous issues by examining the effects of lysergic acid diethylamide (LSD) on creativity using multimodal tasks and multidimensional approaches. Methods:...