Journal of affective disorders
January 15, 2025
Fernanda Palhano-Fontes, Patricia Cavalcanti-Ribeiro, Kaike Thiê da Costa Gonçalves et al.
7 citations
Eight weekly subcutaneous injections of esketamine produced a 52.17% response rate and a 34.78% remission rate in 30 patients with treatment-resistant depression, with improvements in self-reported depressive symptoms sustained for up to six months. The open-label trial lacked a control group and had a small sample size, limiting causal interpretation and generalizability. Subcutaneous administration offers a cheaper, easier alternative to intravenous or intranasal routes with comparable plasma levels and fewer side effects.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
March 1, 2023
Isabel Wießner, Marcelo Falchi, Dimitri Daldegan-Bueno et al.
6 citations
Low to moderate doses of LSD alter language structure, semantics, and vocabulary over time. In a double-blind, placebo-controlled crossover study, 24 healthy volunteers (age 35±11, 33% women) received 50 μg LSD or placebo. LSD reduced verbosity, lexicon, and connectivity in speech networks from 1.5 to 4 hours, decreased semantic distances between words from 2 to 24 hours, and shifted vocabulary related to grammar, persons, time, space, and biological processes from 1.5 to 24 hours. Simpler, disconnected structure and increased semantic similarity may reflect cognitive impairments, while vocabulary changes may indicate subjective perceptual shifts. Automated language analysis could offer unconstrained insights into psychedelic cognition.
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
A systematic review of 29 studies examined whether the psychoactive effects of ketamine are linked to its therapeutic benefits for psychiatric disorders. About half of the studies (51.72%) found a positive relationship between ketamine-induced altered states of consciousness and clinical outcomes, while 44.83% found no link, and one study found a negative association. For mood disorders like major depressive disorder and bipolar disorder, 48% of studies showed a positive relationship and 48% showed none. All three studies on substance use disorder reported a positive correlation. The authors conclude the relationship remains uncertain due to high variability across studies.
medRxiv
January 4, 2024
Marcelo Falchi-Carvalho, Handersson Barros, Raynara Bolcont et al.
5 citations
preprint
A single-day session of vaporized DMT, a psychedelic compound found in ayahuasca, rapidly reduced depression symptoms in six patients with treatment-resistant depression. Depression scores on two standard rating scales dropped substantially by day one and remained lower for one month. By day seven, 83% of patients responded to treatment and 67% achieved remission; at one month, 67% maintained response and 50% maintained remission. The non-invasive, short-acting nature of DMT may make psychedelic treatments more accessible in interventional psychiatry.
bioRxiv (Cold Spring Harbor Laboratory)
January 31, 2018
Ana Cecília de Menezes Galvão, Raíssa Nóbrega de Almeida, Erick Allan Dos Santos Silva et al.
5 citations
preprint
In treatment-resistant depression, a single dose of ayahuasca normalizes the blunted awakening salivary cortisol response that is characteristic of the disorder. Patients with major depression showed hypocortisolemia and a diminished cortisol awakening response compared with healthy controls at baseline. During the dosing session, both patients and controls who ingested ayahuasca had a large increase in salivary cortisol relative to placebo groups. Forty-eight hours after ayahuasca, the awakening cortisol response in treated patients became similar to that of controls, an effect not seen with placebo. No changes in plasma cortisol occurred 48 hours after either ayahuasca or placebo. The modulation of salivary cortisol may contribute to ayahuasca's rapid antidepressant effects.
Journal of Physics Complexity
March 1, 2023
Aline Viol, G. M. Viswanathan, Oleksandra Soldatkina et al.
4 citations
The physical basis of consciousness is a central open question in science. This work compares resting-state functional brain networks of individuals before and after ingesting the psychedelic brew Ayahuasca. Using a measure called pairwise information parity, which quantifies statistical symmetries between brain region connections across the entire network, the authors found an increase in average information parity under psychedelic influence. Notably, information parity between regions of the limbic system and frontal cortex was consistently higher for all individuals while under the influence. These findings suggest that the resemblance of statistical influences between pairs of brain region activities tends to increase under Ayahuasca, possibly as a mechanism to maintain network functional resilience.
Scientific reports
November 10, 2023
Lucas Cruz, Bheatrix Bienemann, Fernanda Palhano-Fontes et al.
3 citations
Ayahuasca, a psychoactive brew used as an entheogen for centuries, is being investigated as a treatment for clinical disorders. This study analyzed open-ended descriptions from nine people with treatment-resistant depression and twenty healthy controls after their first ayahuasca experience. Using quantitative textual analysis, five clusters emerged: altered consciousness, cognitive changes, somatic alterations, auditory experiences, and visual content. People with depression reported more aversive bodily reactions. The findings align with known psychedelic experience patterns and may guide therapeutic use of ayahuasca.
Progress in brain research
January 1, 2025
Handersson Barros, Marcelo Falchi-Carvalho, Lucas O Maia et al.
2 citations
Psychedelic experiences, particularly those from DMT, are often intense and hard to put into words, which complicates therapeutic integration. In a Phase I clinical trial, participants created mandalas as a nonverbal expressive tool. The mandalas helped them symbolically express subjective content that was difficult to verbalize, thereby supporting integration. Despite this promise, expressive tools remain underused in psychedelic clinical protocols. Including art may enhance therapeutic benefits by deepening understanding and meaning of the experience.
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.
Journal of Psychedelic Studies
June 9, 2023
Beatriz Caiuby Labate, Anna O. Ermakova, Jordan Sloshower et al.
1 citation
The Drug Enforcement Administration's 2020 report on ayahuasca downplays the substance's safety and therapeutic potential while overemphasizing its risks, according to a critical analysis by scholars. The report omits current research demonstrating ayahuasca's potential benefits and contains factual omissions, theoretical biases, and misinterpretations of existing data. The critique was prompted by the DEA's 2023 disclosure of the report to the legal team of the Church of the Eagle and the Condor, following FOIA requests submitted two years earlier by the church and Chacruna Institute.
Journal of clinical psychopharmacology
Vagner Deuel de O Tavares, Kaike Thiê da Costa Gonçalves, Maria Luiza de Morais Barros et al.
1 citation
A meta-analysis of eleven studies found no significant correlation between the psychoactive (psychomimetic) effects of ketamine and clinical outcomes in mental illness, including depression. The overall correlation was r = 0.06, and for depression specifically r = 0.03, both non-significant. Sub-analyses accounting for patient disorders, intravenous administration, assessment instruments, and timing also yielded no significant findings. High heterogeneity was present. The analysis suggests that altered states of consciousness during ketamine sessions are not directly linked to clinical outcomes, but the limited number of studies and heterogeneity make this conclusion preliminary.
Journal of Psychopharmacology
July 8, 2026
Raynara Bolcont, Fernanda Palhano-Fontes, Handersson Barros et al.
Inhaled DMT, combined with psychological support, is associated with reduced state anxiety up to one day after administration in both healthy individuals and patients with treatment-resistant depression. Healthy volunteers reported increased life satisfaction up to 14 days. Patients showed increased life satisfaction after 12 months and sustained improvements in quality of life over that period, including physical health, psychological health, social relationships, and environment, as well as inner peace and hope and optimism. The study is limited by an open-label design, lack of placebo control, and modest sample size.
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.
Chaos Solitons & Fractals
May 30, 2026
Tales Ramos Monteiro Dos Santos, Dráulio B. Araújo, Helcio Felippe et al.
Psychedelic states can help researchers understand how the brain reorganizes at a large scale. In nine people scanned before and after taking ayahuasca, topological data analysis of resting-state fMRI connectivity showed a nominal decrease in persistent entropy of H2 features—a measure of higher-dimensional topological structure—that did not survive correction for multiple comparisons and was not reproduced with signed correlations. Exploratory analyses of signal complexity found descriptive but non-significant increases. These preliminary, hypothesis-generating results highlight persistent homology as a potential framework for studying psychedelic-related brain changes, but replication in larger placebo-controlled studies is needed.
Current Addiction Reports
February 21, 2026
Dráulio B. Araújo, Lucas O. Maia, Tiago Arruda-Sanchez et al.
Preclinical and clinical evidence suggests that ayahuasca, a traditional Amazonian brew containing DMT and β-carbolines, may treat depression, anxiety, post-traumatic stress disorder, substance use, eating, and personality disorders. Preclinical studies indicate enhanced neuroplasticity, reduced inflammation, and oxidative stress. Human neuroimaging shows decreased default mode network activity, increased functional connectivity and brain entropy, suggesting a flexible neural state and modulation of pathways related to neuroplasticity, inflammation, and stress response. The evidence is mainly observational, with users reporting emotional breakthroughs, increased self-awareness, and mystical experiences tied to therapeutic outcomes. Ayahuasca appears to target core psychological and neurobiological processes across disorders but requires caution in psychotic or bipolar individuals and should be administered with support. Randomized trials are needed to confirm efficacy and safety.
bioRxiv (Cold Spring Harbor Laboratory)
December 11, 2025
Caroline L. Alves, Fernanda Palhano-Fontes, Thaise G. L. de O. Toutain et al.
Ayahuasca alters conscious experience, and this study identifies EEG markers of its network-level effects using machine learning and complex-network analysis. In a randomized, double-blind, placebo-controlled trial with naïve ayahuasca users, resting-state EEG was recorded before dosing, 2 hours after, and 4 hours after. Connectivity was estimated with sliding windows; optimal classification performance occurred at 60–70 seconds (AUC and accuracy = 0.93). Network analysis revealed a bilateral decrease in eigenvector centrality (weaker hub influence), increased degree heterogeneity in the right hemisphere, and reduced global efficiency in the left. Posterior-left connections weakened acutely, while right temporal–central coupling transiently strengthened. The findings suggest that hub-centric shortcuts weaken, routing communication through more distributed, less efficient pathways with right-lateralized expression.
Journal of Psychopharmacology
December 4, 2025
Natan Silva-Costa, Jéssica Andrade Pessoa, Kátia Cristina Andrade et al.
Ayahuasca produces profound changes in perception, cognition, and emotion, including mystical experiences and altered mind-wandering, while decreasing global alpha brain oscillations and increasing frontomedial delta and right posterior theta and beta. Lower theta during the experience is linked to stronger mystical experiences, and higher alpha is associated with less thought about nothing. Baseline brain activity before taking ayahuasca can predict some subjective effects: lower baseline theta predicts stronger bodily awareness and interoception, and lower baseline beta predicts greater positive emotionality.
Ponto Urbe
December 27, 2024
Beatriz Caiuby Labate, Anna O. Ermakova, Jordan Sloshower et al.
In February 2023, the U.S. Drug Enforcement Administration (DEA) released a 2020 report titled 'Ayahuasca: Risks to Public Health and Safety' to the legal team of the Church of the Eagle and the Condor, following Freedom of Information Act requests. This article challenges several claims in the DEA report, highlighting factual omissions, theoretical biases, and misinterpretations of existing data. The authors argue that the report minimizes ayahuasca's safety profile and therapeutic potential while overemphasizing risks, and fails to include current research demonstrating its potential benefits.
Research Square (Research Square)
August 23, 2023
Lucas Villar Magalhães da Cruz, Bheatrix Bienemann Favero, Fernanda Palhano-Fontes et al.
First-time ayahuasca users with treatment-resistant depression and healthy controls described their subjective experiences in open-ended questions. Textual analysis of responses from nine depressed and 20 healthy individuals revealed five clusters: altered consciousness, cognitive changes, somatic alterations, auditory experiences, and visual perceptual content. Depressed participants reported more aversive bodily reactions, suggesting specific experiential features in depression. The results align with prior psychedelic research and may guide therapeutic applications of ayahuasca.
arXiv Preprint Archive
July 28, 2022
Aline Viol, Gandhi M. Viswanathan, Oleksandra Soldatkina et al.
The physical basis of consciousness remains an open question. Using complex network theory, the study compared resting-state functional brain networks of individuals before and after ingesting the psychedelic brew Ayahuasca. The researchers calculated pairwise information parity to quantify statistical symmetries between brain region connectivity across the entire network. They detected an increase in average information parity in brain networks under psychedelic influence. Notably, information parity between regions of the limbic system and frontal cortex was consistently higher for all individuals while under the influence.
arXiv Preprint Archive
September 26, 2018
A. Viol, Fernanda Palhano-Fontes, Heloisa Onias et al.
A new network metric called geodesic entropy quantifies the Shannon entropy of the distance distribution from each node to all others, capturing the structural role of individual nodes in a network. Applied to functional brain networks of humans in two states of consciousness—ordinary waking and after ingestion of Ayahuasca—the metric distinguished the states. Brain networks under Ayahuasca showed, on average, larger geodesic entropy than those in the ordinary waking state. The authors suggest geodesic entropy is a useful tool for analyzing complex networks and may improve understanding of emergent behaviors such as self-organized criticality.
arXiv Preprint Archive
November 1, 2016
A. Viol, Fernanda Palhano-Fontes, Heloisa Onias et al.
Psychedelic Ayahuasca increases brain network complexity, supporting ancient wisdom about "mind expansion" with modern neuroscience. Brain scans revealed that this Amazonian brew creates more diverse neural connections while strengthening local brain networks. The changes in brain organization showed higher Shannon entropy, indicating more dynamic and flexible thought patterns during the psychedelic experience.