Journal of Affective Disorders
August 10, 2026
Yves Martins Varela, Patrícia Cavalcanti-Ribeiro, Geovan Menezes de Sousa et al.
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...
Journal of Psychopharmacology
July 8, 2026
Raynara Bolcont, Fernanda Palhano-Fontes, Handersson Barros et al.
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...
Neuropharmacology
July 1, 2026
Anne 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...
Journal of Psychiatric Research
July 1, 2026
K S de Freitas Goncalves, Vagner Deuel O de Tavares, Fernanda Palhano-Fontes et al.
ABSTRACT: Introduction Ketamine and esketamine have reemerged as promising interventions for treatment-resistant depression (TRD), yet debate persists regarding the clinical relevance of acute dissociative experiences. This secondary exploratory analysis examined the relationship between dissociative experiences induced by subcutaneous esketamine and antidepressant response in patients with...
medRxiv Preprint Server
May 31, 2026
Yves Martins Varela, Patrícia Cavalcanti-Ribeiro, Geovan Menezes de Sousa et al.
preprint
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...
Chaos Solitons & Fractals
May 30, 2026
Tales Ramos Monteiro Dos Santos, Draulio B Araujo, Helcio Felippe et al.
Psychedelic states offer a useful setting for studying changes in large-scale brain organization. Here, we applied Topological Data Analysis (TDA) to resting-state fMRI functional connectivity from nine participants scanned before and after Ayahuasca ingestion. Vietoris–Rips filtrations were constructed from correlation-derived dissimilarity matrices, and persistent entropy was used to quantify...
Research Square
May 20, 2026
Isabel Wießner, Marcelo Falchi-Carvalho, Sophie Laborde et al.
DMT, Madness, and Healing: Psychosis Model, Therapy Model, and Their Relations to Mystical Experiences and Positive Emotionality
Nature Medicine
April 1, 2026
Manesh Girn, Manoj K. Doss, Leor Roseman et al.
8 citations
Psychedelic drugs are re-emerging as promising scientific and clinical tools. However, despite a rapidly expanding literature on their therapeutic value, the neural mechanisms underlying psychedelic effects remain unclear. Resting-state functional magnetic resonance imaging studies of acute psychedelic effects, conducted independently by several research groups, have so far yielded fragmented...
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
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...
Journal of Affective Disorders
March 15, 2026
Patrícia Cavalcanti-Ribeiro, Lara Carvalho Araújo Melo De Souza, Vagner Deuel O de Tavares et al.
Treatment-resistant depression (TRD) remains a major clinical challenge, with inflammation increasingly implicated in its pathophysiology. C-reactive protein (CRP), an accessible biomarker, has emerged as a potential predictor of antidepressant response. While intravenous and intranasal ketamine have shown anti-inflammatory effects, evidence linking inflammation and clinical outcomes remains...
Current Addiction Reports
February 21, 2026
Draulio B Araujo, Lucas O. Maia, Tiago Arruda Sanchez et al.
Summarizes preclinical and clinical evidence on ayahuasca—a traditional Amazonian brew combining N, N-Dimethyltryptamine (DMT) and β-carbolines—in treating depression, anxiety, post-traumatic stress disorder, substance use, eating, and personality disorders. Preclinical work shows enhanced neuroplasticity, reduced inflammation, and oxidative stress. Human neuroimaging reveals decreased default...
bioRxiv (Cold Spring Harbor Laboratory)
December 11, 2025
Caroline L. Alves, Fernanda Palhano-Fontes, Thaise G. L. de O. Toutain et al.
Abstract Ayahuasca profoundly alters conscious experience, yet robust, time-resolved EEG markers of its network-level effects remain limited. We combined machine learning with complex-network analysis to quantify how functional connectivity reorganizes across time and hemispheres in resting-state EEG from a randomized, double-blind, placebo-controlled trial including three 5-min sessions:...
Journal of Psychopharmacology
December 4, 2025
Natan Silva-Costa, Jéssica Andrade Pessoa, Kátia Cristina Andrade et al.
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,...
Nature Communications
August 13, 2025
William Wong, Rubén Herzog, Kátia Cristine Andrade et al.
10 citations
Magneto/electroencephalography (M/EEG) studies of dreaming are an essential paradigm in the investigation of neurocognitive processes of human consciousness during sleep, but they are limited by the number of observations that can be collected per study. Dream research also involves substantial methodological and conceptual variability, which poses problems for the integration of results. To...
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
June 17, 2025
Isabel Wießner, Marcelo Falchi-Carvalho, Sophie Laborde et al.
7 citations
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...
Nature Medicine
June 3, 2025
Chloé Pronovost-Morgan, Kyle T. Greenway, Leor Roseman et al.
26 citations
Psychedelic substances exhibit complex interactions with the 'set and setting' of use, that is, the mental state of the user and the environment in which a psychedelic experience takes place. Despite these contextual variables' known importance, psychedelic research has lacked methodological rigor in reporting extra-pharmacological factors. This study aimed to generate consensus-based...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
May 1, 2025
Marcelo Falchi-Carvalho, Fernanda Palhano-Fontes, Isabel Wießner et al.
35 citations
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...
Psychedelic medicine (New Rochelle, N.Y.)
March 1, 2025
Marcelo Falchi-Carvalho, Handersson Barros, Raynara Bolcont et al.
16 citations
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)...
Journal of Affective Disorders
January 15, 2025
Fernanda Palhano-Fontes, Patrícia Cavalcanti-Ribeiro, Kaike Thiê da Costa Gonçalves et al.
7 citations
Ketamine has gained prominence as one of the most effective therapeutic options in unipolar treatment-resistant depression (TRD). However, most studies related to the antidepressant action of ketamine used intravenous (IV) or intranasal (IN) administration. The subcutaneous (SC) route of administration is a promising alternative, as it results in plasma levels comparable to IV, causes fewer...
Progress in Brain Research
2025
Handersson Barros, Marcelo Falchi-Carvalho, Lucas O. Maia et al.
2 citations
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...
Ponto Urbe
December 27, 2024
Beatriz Caiuby Labate, Anna O. Ermakova, Jordan Sloshower et al.
Em fevereiro de 2023, a Drug Enforcement Administration (DEA) divulgou um documento para a equipe jurídica que representa a Church of the Eagle and the Condor (“CEC”). Essa divulgação ocorreu dois anos depois que a igreja, em conjunto com o Chacruna Institute, enviou duas solicitações baseadas na lei de liberdade de informação [Freedom Of Information Act] à DEA e ao Departamento de Justiça...
European Archives of Psychiatry and Clinical Neuroscience
October 28, 2024
Kaike Thiê da Costa Gonçalves, Vagner Deuel O de Tavares, Maria Luiza de Morais Barros et al.
5 citations
This systematic review aims to elucidate the nexus between ketamine's psychoactive properties and its efficacy in treating a broad spectrum of psychiatric disorders. We searched three databases and used citation tracking to include 29 studies. Predominantly, mood disorders, including bipolar disorder (BD) and major depressive disorder (MDD) (MDD + BD: + n = 25 studies), a large part of them...
Journal of Psychiatric Research
August 1, 2024
Eduardo Igor Torquato Cardoso Lopes, Patrícia Cavalcanti-Ribeiro, Fernanda Palhano-Fontes et al.
9 citations
Therapeutics for suicide management is limited, taking weeks to work. This open-label clinical trial with 18 treatment-resistant depressive patients tested subcutaneous esketamine (8 weekly sessions) for suicidality. We noted a rapid and enduring effect of subcutaneous esketamine, lasting from one week to six months post-treatment, assessed by the Beck Inventory for Suicidality (BSI). There was...
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
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...
medRxiv
January 4, 2024
Marcelo Falchi-Carvalho, Handersson Barros, Raynara Bolcont et al.
5 citations
preprint
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,...