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.
Frontiers in Psychiatry
December 5, 2022
Geovan Menezes de Sousa, Vagner Deuel de Oliveira Tavares, Ana Cecília de Menezes Galvão et al.
14 citations
In a double-blind, placebo-controlled trial with 72 participants, ayahuasca's effects on depression-related biomarkers were examined two days after dosing. Larger reductions in depressive symptoms during the session were linked to higher serum cortisol levels in patients with treatment-resistant depression. Smaller changes in salivary cortisol during ayahuasca use were associated with higher brain-derived neurotrophic factor (BDNF) levels in patients who showed greater clinical improvement in depressive symptoms. No moderating effects were found for the cortisol awakening response, interleukin-6, or C-reactive protein in patients, nor for any biomarker in healthy controls or the placebo group. The findings suggest that acute emotional and physiological responses during ayahuasca sessions may influence key biomarkers of depression.
Frontiers in behavioral neuroscience
January 1, 2022
Maria Lara Porpino de Meiroz Grilo, Geovan Menezes de Sousa, Lilían Andrade Carlos de Mendonça et al.
12 citations
Repeated ayahuasca administration before and during social isolation prevented depressive-like behaviors and cortisol alterations in common marmosets. Animals given ayahuasca showed higher cortisol reactivity and fecal cortisol levels similar to family-group controls, no signs of anhedonia, and no increase in chronic stress-related behaviors, unlike isolated animals that received no intervention. The findings suggest ayahuasca promotes resilient responses and may have a prophylactic action against depression.
Journal of psychiatric research
August 1, 2024
Eduardo Igor Torquato Cardoso Lopes, Patrícia Cavalcanti-Ribeiro, Fernanda Palhano-Fontes et al.
9 citations
Subcutaneous esketamine injections given weekly for eight weeks produced a rapid and lasting reduction in suicidality among 18 adults with treatment-resistant depression. Suicidal thoughts dropped within 24 hours after the first dose and remained low throughout the eight-week treatment period. At six months after treatment ended, suicidality was still consistently lower. Clinician ratings showed significant improvement only after two sessions, and 61% of patients achieved remission from suicidal ideation. The findings suggest that weekly subcutaneous esketamine may be a cost-effective way to achieve fast and sustained anti-suicide effects, but controlled studies are needed to confirm these initial observations.
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.
Frontiers in neuroanatomy
January 1, 2025
Wigínio Gabriel de Lira-Bandeira, Lílian Andrade Carlos de Mendonça Batista, Andréa Silva de Medeiros Bandeira et al.
4 citations
Chronic social isolation in marmosets leads to significant shrinkage of neurons in the striatum, a brain region that integrates emotion, motivation, and movement. Ayahuasca, a psychoactive plant-based brew, given before and during isolation, prevented this neuronal volume loss. The caudate and putamen of socially isolated animals treated with ayahuasca showed neuron sizes comparable to those of family-housed controls, while untreated isolated animals had markedly smaller neurons. The findings suggest ayahuasca may act as a prophylactic buffer against stress-induced structural brain changes.
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.
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.
Translational Psychiatry
February 19, 2026
Luís Carlos Pereira, Wigínio Gabriel Lira-Bandeira, Andréa Silva Medeiros-Bandeira et al.
Chronic stress from social isolation in juvenile male marmosets reduces neuronal volume in the somatosensory cortex, a brain region implicated in depression. Ayahuasca, a psychedelic brew, given before and during isolation prevented this reduction, with treated animals showing neuronal volumes similar to non-stressed controls. Trends also suggested preserved cortical structure, though differences in neuronal density and overall cortical volume were not statistically significant. These results indicate ayahuasca may protect against stress-induced cortical atrophy and support further research into its therapeutic potential for stress-related psychiatric disorders, especially in adolescents.