European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
January 1, 2023
Lucas Oliveira Maia, Dimitri Daldegan-Bueno, Isabel Wießner et al.
46 citations
Ayahuasca shows therapeutic potential for depression and substance use disorders, with growing preliminary evidence for grief, eating disorders, posttraumatic stress disorder, personality disorders, Parkinson's and Alzheimer's disease, and severe physical illnesses like cancer and chronic conditions. Long-term regular use does not appear detrimental and may benefit individual and collective health. The evidence for depression and substance use disorders is most consistent, while other conditions represent promising targets requiring further rigorous investigation.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
May 1, 2022
Isabel Wießner, Rodolfo Olivieri, Marcelo Falchi et al.
42 citations
A low dose of LSD (50 μg) produces both beneficial and detrimental cognitive effects 24 hours after administration. Compared to placebo, LSD sub-acutely improved visuospatial memory and phonological verbal fluency but impaired cognitive flexibility, as measured by fewer categories achieved and more perseveration on the Wisconsin Card Sorting Test. The findings suggest that LSD-assisted therapy might be explored for conditions involving memory and language decline, such as brain injury, stroke, or dementia, while also indicating a mixed 'afterglow and hangover' profile.
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).
Current Topics in Behavioral Neurosciences
January 1, 2022
Fernanda Palhano-Fontes, Bruno Lobão‐soares, Nicole Leite Galvão‐coelho et al.
25 citations
Ayahuasca, a psychedelic brew containing DMT and MAOIs, shows rapid antidepressant effects in clinical trials. Evidence from open and placebo-controlled studies indicates significant improvement starting as early as one day after administration. This article reviews the history, pharmacology, clinical trials, and behavioral markers of ayahuasca's antidepressant properties.
medRxiv
September 29, 2019
Lorenzo Pasquini, Fernanda Palhano-Fontes, Draulio B Araujo
24 citations
preprint
One day after a single session with the psychedelic ayahuasca, connectivity within and between brain networks that support interoception, emotion, and self-related thought is altered compared to placebo. In a randomized trial with 22 participants receiving ayahuasca and 21 receiving placebo, the ayahuasca group showed increased connectivity within the salience network, decreased connectivity within the default mode network, and increased connectivity between these two networks. Primary sensory networks were not affected. These connectivity changes correlated with acute subjective effects such as altered body awareness, volition, and affect. The findings suggest that ayahuasca induces subacute functional reorganization of higher-order cognitive brain networks.
Psychopharmacology
June 1, 2022
Isabel Wießner, Marcelo Falchi, Fernanda Palhano-Fontes et al.
22 citations
LSD alters the stream of thought in multiple ways, increasing chaos, meaning, and abstractness at different times after ingestion. In a randomized, double-blind, placebo-controlled crossover study with 24 healthy participants, 50 μg LSD compared to placebo induced facets of mind-wandering labeled 'chaos' (discontinuity of mind, decreased sleepiness and planning), 'meaning' (deep thoughts), and 'sensation' (thoughts about odors and sounds). LSD also increased free association for abstract words, reflecting an 'abstract flow.' Chaos was strongest from 2 to 6 hours after dosing, meaning from 2 to 4 hours, sensation at 2 hours, and abstract flow at 4 hours. The findings suggest a late therapeutic window around 4 hours for psycholytic therapy.
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.
Nature Medicine
April 1, 2026
Manesh Girn, Manoj K. Doss, Leor Roseman et al.
8 citations
Psychedelic drugs are being studied again for their therapeutic potential, but how they change brain function is not well understood. By combining 11 brain-scanning datasets from five different psychedelics (psilocybin, LSD, mescaline, DMT, and ayahuasca) across three continents, researchers found a common pattern: increased communication between brain networks that handle high-level thinking (default, frontoparietal, and limbic) and those that handle sensory input (visual and somatomotor). Key deep-brain regions (thalamus, caudate, putamen) and the cerebellum also changed how they connect with sensorimotor networks. Contrary to some earlier studies, reductions in within-network connectivity were weak to moderate and varied by drug. These findings help resolve previous inconsistencies and provide a comprehensive map of how psychedelics alter large-scale brain organization.
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 Affective Disorders
January 15, 2025
Fernanda Palhano-Fontes, Patrícia 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.
Frontiers in Psychiatry
January 1, 2022
Otto Simonsson, José Carlos Bouso, Florian Kurth et al.
6 citations
The corpus callosum, a brain structure connecting the two hemispheres, was thicker in the isthmus region among 22 ayahuasca users compared to 22 matched controls. A positive correlation was observed between callosal thickness in the rostral body and the number of past ayahuasca sessions, though neither finding survived correction for multiple comparisons. No brain region was thicker in controls than in ayahuasca users, and no region was negatively linked to ayahuasca use. This provides preliminary evidence of an association between ayahuasca use and callosal structure, but replication with larger samples and longitudinal designs is needed.
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.
Chaos Solitons & Fractals
May 30, 2026
Tales Ramos Monteiro Dos Santos, Draulio B Araujo, 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.
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.
Current Addiction Reports
February 21, 2026
Draulio B Araujo, 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.
Functional & integrative genomics
December 30, 2024
Vitor Trinca, Saura R Silva, João V A Almeida et al.
The plastid genome of Mimosa tenuiflora (Jurema-Preta) is 165,639 base pairs long with a typical quadripartite structure and 130 protein-coding genes. Its mitochondrial genome is 617,839 base pairs, contains 107 protein-coding genes, and shows complex structural rearrangements from large repeats, including transferred plastid genes and sequences from non-retroviral RNA mitoviruses. Comparative analysis across Fabaceae species indicates limited conservation, highlighting the dynamic evolution of plant mitochondrial genomes. Phylogenetic placement confirms M. tenuiflora within Caesalpinioideae, closely related to M. pigra and M. pudica. The genomic characterization provides insights for evolutionary studies, population genetics, and potential ethnopharmacological applications.