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 Gonzalez 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.
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.
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.
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.
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.
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.
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.
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.