Psychological Medicine
June 15, 2018
Fernanda Palhano-Fontes, Dayanna Barreto, Heloisa Onias et al.
827 citations
A single dose of ayahuasca reduced depression severity more than placebo in patients with treatment-resistant depression. Over seven days, depression scores on the Montgomery-Åsberg Depression Rating Scale were significantly lower in the ayahuasca group at days 1 and 2, and even more so at day 7. Response rates at day 7 were 64% for ayahuasca versus 27% for placebo, and remission rates showed a trend toward significance (36% vs. 7%). Effect sizes grew from day 1 to day 7, indicating sustained improvement. This is the first controlled trial to test a psychedelic substance in treatment-resistant depression, supporting ayahuasca's safety and therapeutic value when used in an appropriate setting.
Frontiers in Psychiatry
May 8, 2018
Ana Cecília de Menezes Galvão, Raíssa Nóbrega de Almeida, Erick Allan Dos Santos Silva et al.
102 citations
In treatment-resistant depression, a single dose of ayahuasca normalizes the blunted awakening salivary cortisol response observed in patients, bringing it to levels similar to those in healthy controls. During the dosing session, both patients and healthy volunteers who received ayahuasca showed higher increases in salivary cortisol than those who received placebo. No significant changes in plasma cortisol were detected 48 hours after dosing. These findings suggest that ayahuasca modulates salivary cortisol, a hormone involved in depression's etiology, and support further investigation into its antidepressant potential.
Frontiers in Pharmacology
November 19, 2019
Richard J. Zeifman, Fernanda Palhano-Fontes, Jaime E. C. Hallak et al.
79 citations
A single dose of ayahuasca, compared with placebo, was associated with medium-to-large reductions in suicidality among 29 adults with treatment-resistant depression. Suicidality was assessed by a psychiatrist before the intervention and at one, two, and seven days afterward. The between-group effect sizes (ayahuasca versus placebo) were medium at each time point (Cohen's d = 0.58, 0.56, and 0.67), and the within-group effect sizes for those receiving ayahuasca were large (Cohen's d = 1.33, 1.42, and 1.19). The group-by-time interaction was not statistically significant, suggesting the findings should be interpreted cautiously. The authors conclude that ayahuasca may hold potential as an intervention for suicidality, while noting important limitations and the need for further research.
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.
bioRxiv (Cold Spring Harbor Laboratory)
January 27, 2017
Fernanda Palhano-Fontes, Dayanna Barreto, Heloisa Onias et al.
22 citations
preprint
A single dose of ayahuasca produced significant antidepressant effects in patients with treatment-resistant depression compared to placebo. Depression severity, measured by the Montgomery–Åsberg Depression Rating Scale (MADRS), was significantly lower in the ayahuasca group at one, two, and seven days after dosing. Effect sizes increased over time, reaching a Cohen's d of 1.49 at day seven. Response rates were significantly higher in the ayahuasca group at day seven (64% vs. 27%), and remission rates were marginally significant (36% vs. 7%). This controlled trial supports the safety and therapeutic value of ayahuasca in treating depression.
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.
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 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.