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 Psychology
June 4, 2019
Raíssa Nóbrega de Almeida, Ana Cecília de Menezes Galvão, Flávia Santos Da Silva et al.
173 citations
A single dose of ayahuasca increased serum brain-derived neurotrophic factor (BDNF) levels in both healthy controls and patients with treatment-resistant depression 48 hours after ingestion, compared with placebo. Baseline BDNF levels did not predict major depression or clinical characteristics, but lower BDNF was linked to hypocortisolemia. Among patients, only those who received ayahuasca showed a negative correlation between BDNF levels and depressive symptoms at 48 hours. The findings suggest a potential link between ayahuasca's antidepressant effects and changes in BDNF, supporting further investigation into psychedelics for depression.
Psychopharmacology
January 11, 2021
Nicole Leite Galvão‐coelho, Wolfgang Marx, Maria González et al.
143 citations
Classic serotonergic psychedelics such as psilocybin, LSD, and ayahuasca may improve mood and reduce depressive symptoms more than placebo, with effects appearing within hours and lasting up to 60 days. A meta-analysis of 12 randomized controlled trials involving 257 participants (124 healthy volunteers and 133 patients with mood disorders) found moderate significant effect sizes favoring psychedelics for acute mood improvements in both groups and for longer-term mood benefits in patients. For patients with mood disorders, significant reductions in depressive symptoms were seen acutely, at 2–7 days, and at 16–60 days after treatment. Although unblinding and expectancy are concerns, the strength, speed, and durability of effects support further placebo-controlled trials.
Journal of Psychopharmacology
July 10, 2020
Nicole Leite Galvão‐coelho, Ana Cecília de Menezes Galvão, Raíssa Nóbrega de Almeida et al.
124 citations
In a double-blind placebo-controlled trial, people with treatment-resistant depression had higher baseline levels of C-reactive protein than healthy controls, and a negative correlation between C-reactive protein and cortisol was observed. Ayahuasca, but not placebo, reduced C-reactive protein levels in both patients and healthy controls 48 hours after ingestion. Among patients treated with ayahuasca, larger reductions in C-reactive protein correlated with lower depressive symptoms. No significant changes were found for interleukin 6 or brain-derived neurotrophic factor, and these biomarkers did not predict antidepressant response or remission. The findings clarify biological mechanisms underlying ayahuasca's antidepressant effects.
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.
Front Pharmacol
April 21, 2021
Daniel Perkins, Violeta Schubert, Hana Šimonová et al.
73 citations
A large international survey of ayahuasca drinkers found that the context and setting in which ayahuasca is consumed—including preparation, guidance, and integration support—are strongly associated with mental health and wellbeing outcomes. Participants who reported professional or traditional guidance, structured preparation, and post-session integration were more likely to experience improvements in mood, reductions in anxiety, and overall psychological wellbeing. The findings suggest that the benefits of ayahuasca are not solely due to the substance itself but are significantly influenced by the surrounding environmental and support factors. Negative or null outcomes were more common among those who lacked such structured support.
Journal of Affective Disorders Reports
February 6, 2021
Jerome Sarris, Daniel Perkins, Lachlan Cribb et al.
72 citations
Among 1,571 people who reported depression and 1,125 who reported anxiety at the time of consuming ayahuasca, 78% of those with depression said their symptoms were 'very much' improved (46%) or 'completely resolved' (32%), while 70% of those with anxiety reported 'very much' improvement (54%) or complete resolution (16%). Greater improvement was linked to mystical experiences, more ayahuasca sessions, and personal psychological insights. A small minority—2.7% with depression and 4.5% with anxiety—reported worsened symptoms. The authors note this cross-sectional survey cannot establish treatment efficacy and call for randomized controlled trials.
Drug and Alcohol Review
July 25, 2021
Daniel Perkins, Emérita Sátiro Opaleye, Hana Šimonová et al.
54 citations
People who consumed ayahuasca in naturalistic settings reported lower current use of alcohol and other drugs, including risky drinking, compared to those who used it less often. The more times ayahuasca was consumed, the stronger the association with never or rarely drinking alcohol and not using a range of drugs in the past month. These effects were greater for individuals with a prior substance use disorder. The strength of subjective spiritual experience, number of personal insights gained, and drinking ayahuasca with an ayahuasca church were also linked to lower substance use in some analyses. The associations remained after adjusting for religious or social group effects.
Australian & New Zealand Journal of Psychiatry
March 21, 2021
Daniel Perkins, Jerome Sarris, Susan L. Rossell et al.
53 citations
Psychedelic substances such as psilocybin, ayahuasca, LSD, and MDMA are gaining renewed medical interest due to the need for new psychiatric treatments and promising study results. This viewpoint reflects on the Royal Australian and New Zealand College of Psychiatrists' Clinical Memorandum on Psychedelics and notes regulatory developments, including applications for down-scheduling and access approvals. The authors argue that rigorous research is needed to assess benefits, safety, and therapeutic mechanisms. They summarize recent findings on mechanisms of action and the psychedelic-assisted psychotherapy model, suggesting medicinal psychedelics could become a new class of psychiatric treatments when used under medical supervision with psychotherapeutic support. However, sufficiently powered trials and safety protocols are required before clinical use, and untrained practitioner access could be harmful.
Brazilian Journal of Psychiatry
November 21, 2018
Flávia S. Da Silva, Erick Allan Dos Santos Silva, Geovan Menezes de Sousa et al.
46 citations
In a juvenile marmoset model of depression, a single dose of ayahuasca reversed stress-induced hypocortisolemia within 24 hours, reduced stereotypic scratching in males, increased feeding in males, and restored body weight in both sexes, with behavioral effects lasting up to 14 days. Saline vehicle did not produce these effects. The findings suggest ayahuasca may have rapid and sustained antidepressant properties, supporting further research into psychedelics for early-onset depression.
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.
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.
Current Opinion in Psychiatry
November 15, 2021
Jerome Sarris, Diego Pinzon Rubiano, Kimberley Day et al.
12 citations
Serotonergic psychedelics, including psilocybin, ayahuasca, LSD, and MDMA, show promise for treating mood disorders and PTSD, often combined with psychotherapy. Psilocybin with psychological support has been effective for depression, including treatment-resistant cases, in randomized placebo-controlled trials. LSD has shown anxiolytic effects, and MDMA has Phase III evidence for PTSD. Microdosing has not been found to improve mood in a controlled trial. Challenges remain with blinding, small sample sizes, and lack of definitive Phase III studies (except MDMA for PTSD). Further research into novel formulations, pharmacogenomics, microbiome interactions, and inflammatory pathways is needed.
January 1, 2021
Fernanda Palhano-Fontes, Sérgio Mota-Rolim, Bruno Lobão‐soares et al.
11 citations
Ayahuasca shows promise as a potent alternative medicine for treating depression and anxiety. In a study involving 100 participants, 70% reported significant mood improvements after just one session, outperforming traditional antidepressants. Biochemical analysis revealed that ayahuasca influences neurotransmitter receptors, potentially reshaping behavior and emotional well-being. Participants also noted reduced symptoms of anxiety, highlighting its potential in psychiatry. This suggests psychedelics could play a vital role in future drug studies, offering new avenues for mental health treatment beyond conventional methods.
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, 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.
Frontiers in Behavioral Neuroscience
June 11, 2021
Maria Bernardete Cordeiro de Sousa, Maria Lara Porpino de Meiroz Grilo, Nicole Leite Galvão‐coelho
7 citations
Marmosets, studied in their natural habitat using non-invasive fecal hormone measurements, are mainly monogamous, live in stable social groups with female competition and male cooperation, and form social bonds similar to humans, making them a potential model for social stress disorders. Laboratory studies confirm these behaviors and show sexually dimorphic responses to challenges influenced by age and social context. Their good adaptation to captivity, twin births, small size, and life cycle advantages have led to their use as animal models for psychiatric diseases like major depression. Juvenile marmosets have been used to develop a depression model and test Ayahuasca as an alternative treatment, with positive results encouraging further studies.
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.
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.
bioRxiv (Cold Spring Harbor Laboratory)
January 25, 2018
Flávia Santos Da Silva, Erick Allan Dos Santos Silva, Geovan Menezes de Sousa et al.
4 citations
preprint
In a juvenile model of depression using common marmosets, a single dose of ayahuasca reversed depressive-like symptoms within 24 hours, including recovery of cortisol levels, reduced stereotypic scratching in males, increased feeding, and restored body weight in both sexes. The effects lasted 14 days. The study suggests ayahuasca produces faster and more durable antidepressant effects than the tricyclic antidepressant nortriptyline, supporting its potential as a treatment for early-age depression.
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.