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.
Brazilian Journal of Psychiatry
March 1, 2015
Flávia de Lima Osório, Rafael Faria Sanches, Ligia Ribeiro Horta de Macedo et al.
486 citations
A single dose of ayahuasca produces fast-acting reductions in anxiety and depression symptoms in people diagnosed with a depressive disorder.
Journal of Clinical Psychopharmacology
December 11, 2015
Rafael Faria Sanches, Flávia de Lima Osório, Rafael G. Dos Santos et al.
468 citations
A single oral dose of ayahuasca, an Amazonian brew containing dimethyltryptamine and harmine, produced fast-acting and sustained reductions in depression severity among 17 patients with recurrent depression. Scores on the Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, and Brief Psychiatric Rating Scale decreased significantly from 80 minutes through 21 days after intake. Brain imaging showed increased blood flow in the left nucleus accumbens, right insula, and left subgenual area—regions involved in mood regulation. Vomiting occurred in 47% of participants, but no other adverse effects were reported. The authors suggest ayahuasca may have antidepressant properties but call for replication in randomized, double-blind, placebo-controlled trials.
Archives of General Psychiatry
February 1, 2008
J.f.w. Deakin, Jane Lees, Shane Mckie et al.
315 citations
Ketamine, which blocks NMDA glutamate receptors and secondarily increases glutamate release, produces psychosis-like symptoms. Using fMRI, a double-blind crossover study with 33 healthy men found that ketamine caused a rapid decrease in ventromedial frontal cortex activity that predicted dissociative effects, and increased activity in posterior cingulate, thalamus, and temporal regions that correlated with psychosis scores. Pretreatment with lamotrigine, a glutamate release inhibitor, prevented many brain changes and symptoms. The findings suggest ketamine's effects involve increased glutamate release and may model two core psychosis processes: abnormal perceptions and impaired cognitive-emotional evaluation.
Therapeutic Advances in Psychopharmacology
March 18, 2016
Rafael G. Dos Santos, Flávia de Lima Osório, José Alexandre S. Crippa et al.
306 citations
A systematic review of clinical trials from 1990 to 2015 examined the therapeutic potential of ayahuasca, psilocybin, and LSD for mood and anxiety disorders and drug dependence. Six trials met inclusion criteria. The reviewed studies suggest beneficial effects for treatment-resistant depression, anxiety and depression associated with life-threatening diseases, and tobacco and alcohol dependence. All drugs were well tolerated. However, all studies had small sample sizes, and half were open-label, proof-of-concept studies. The authors conclude these substances may be useful pharmacological tools, but randomized, double-blind, placebo-controlled studies with more patients are needed to replicate preliminary findings.
Human Brain Mapping
September 16, 2011
Dráulio Barros de Araújo, Sidarta Ribeiro, Guillermo Cecchi et al.
241 citations
Ayahuasca, a hallucinogenic brew containing serotonergic agonists and reuptake inhibitors, triggers vivid visual imagery during ceremonies. Using functional magnetic resonance imaging while participants performed a closed-eyes imagery task, the brew produced a robust increase in activation across occipital, temporal, and frontal brain areas. In the primary visual area, activation levels matched those of natural image viewing with eyes open. This effect correlated with individual perceptual changes measured by psychiatric scales. Activity in areas BA30 and BA37, linked to episodic memory and contextual associations, was also potentiated. Modulation of BA10, involved in prospective imagination and working memory, was detected. The findings suggest Ayahuasca seeings arise from an extensive network for vision, memory, and intention, lending a sense of reality to inner experiences.
Expert Review of Clinical Pharmacology
August 13, 2018
Rafael G. Dos Santos, José Carlos Bouso, Miguel Ángel Alcázar‐córcoles et al.
231 citations
Serotonergic hallucinogens/psychedelics such as ayahuasca, psilocybin, and LSD show promise for reducing anxiety, depression, and substance dependence. Psilocybin and LSD reduced anxiety and depression in cancer patients and symptoms of alcohol and tobacco dependence; ayahuasca reduced depression symptoms in treatment-resistant depression. However, many studies were open-label, few were randomized controlled trials, most had small sample sizes and short duration. Single or few doses appear well tolerated, but long-term studies are lacking. New RCTs with larger samples and longer duration are needed to confirm these findings.
European Neuropsychopharmacology
January 16, 2015
José Carlos Bouso, Fernanda Palhano-Fontes, Antoni Rodrı́guez-fornells et al.
221 citations
Regular use of the psychedelic brew ayahuasca is associated with thinning of the posterior cingulate cortex (PCC), a key hub of the default mode network. In a comparison of 22 regular ayahuasca users and 22 matched controls, MRI scans revealed significant cortical thinning in midline brain structures among users. The degree of thinning correlated with both the intensity and duration of ayahuasca use and with scores on self-transcendence, a personality trait linked to spirituality and transpersonal feelings. While direct causation cannot be established, the findings suggest that sustained psychedelic use may induce structural brain changes underlying attentional processes, self-referential thought, and previously reported personality shifts in long-term users.
The International Journal of Neuropsychopharmacology
May 17, 2017
Frederic Sampedro, Mario de la Fuente Revenga, Marta Valle et al.
205 citations
A single dose of ayahuasca reduced glutamate+glutamine, creatine, and N-acetylaspartate+N-acetylaspartylglutamate in the posterior cingulate cortex of 16 healthy volunteers, measured post-acutely with magnetic resonance spectroscopy. Connectivity increased between the posterior and anterior cingulate cortex, and between the anterior cingulate cortex and limbic structures in the right medial temporal lobe. Reduced glutamate+glutamine correlated with higher scores on the nonjudging subscale of the Five Facets Mindfulness Questionnaire, and increased anterior cingulate cortex-medial temporal lobe connectivity correlated with higher self-compassion scores. Post-acute neural changes predicted sustained elevations in nonjudging two months later, suggesting glutamate neurotransmission and altered default mode network connectivity underlie ayahuasca's psychological effects.
Current Neuropharmacology
March 2, 2018
Jonathan Hamill, Jaime E. C. Hallak, Serdar Dursun et al.
179 citations
Ayahuasca is a traditional Amazonian brew made from Banisteriopsis caapi vine and Psychotria viridis leaves, containing beta-carboline alkaloids and the hallucinogen DMT. Originally used by indigenous shamans for spiritual and healing purposes, it has been incorporated into folk medicine and religious ceremonies in Brazil and is now also used recreationally in Europe and North America. This review summarizes ayahuasca's behavioral and physiological effects, safety profile, proposed mechanisms, and potential clinical uses for psychiatric disorders and addictions. The side effect profile appears relatively mild, but more detailed studies are needed. Some researchers advocate relaxing government regulations to allow comprehensive clinical trials.
Therapeutic Advances in Psychopharmacology
February 23, 2017
Rafael G. Dos Santos, José Carlos Bouso, Jaime E. C. Hallak
167 citations
Ayahuasca, a hallucinogenic brew from the Northwestern Amazon, contains DMT, which acts on serotonin 5-HT2A receptors similarly to LSD and psilocybin. Controlled use of these substances is rarely linked to psychotic episodes, but little is known about use outside controlled settings. A systematic review of case reports identified three case series and two case reports of psychotic episodes after ayahuasca use, and three case reports after DMT use. Many cases involved individuals with personal or family histories of psychosis or other drug use, though some episodes occurred in people without such histories. Overall, psychotic episodes appear rare in both ritual and recreational settings. Psychiatric screening before hallucinogen administration in controlled settings may reduce adverse reactions; individuals with personal or family histories of psychotic illness or mania should avoid hallucinogens.
Brazilian Journal of Psychiatry
March 1, 2016
Rafael G. Dos Santos, Flávia de Lima Osório, José Alexandre S. Crippa et al.
158 citations
Ayahuasca and its alkaloids show promise as potential treatments for anxiety and depression, offering a possible alternative to current drugs that often have adverse effects. The abstract calls for further investigation into these compounds to develop more effective and safer therapies.
Neuroscience & Biobehavioral Reviews
February 13, 2018
José Carlos Bouso, Rafael G. Dos Santos, Miguel Ángel Alcázar‐córcoles et al.
135 citations
Psychedelics significantly enhance personality traits, particularly openness to experience. In a sample of 500 participants, those who used hallucinogens reported a 60% increase in openness, linked to serotonergic activity affecting the posterior cingulate cortex. This suggests that psychedelics influence neurotransmitter receptors, shaping behavior and personality. The findings align with clinical psychology principles, highlighting the potential for these substances in therapeutic settings. Chemical synthesis of alkaloids in psychedelics may provide valuable insights into human psychology and behavior modification.
Scientific Reports
March 5, 2020
José Carlos Bouso, Daniel Jiménez‐garrido, María de Lourdes Gómez-sousa et al.
111 citations
Ayahuasca, a hallucinogenic decoction used in traditional Amazonian medicine, may have therapeutic benefits for psychiatric disorders. In a study of 40 first-time users, nearly half (45%) initially met criteria for a psychiatric disorder; after ayahuasca use, more than 80% of those showed clinical improvements that persisted at 6 months. Questionnaires indicated significant reductions in depression and psychopathology. Long-term users (n=23) had lower depression scores and higher self-transcendence and quality of life compared to first-time users. The authors suggest further controlled and observational studies are warranted to assess risks and benefits.
Journal of Psychoactive Drugs
May 26, 2016
Amanda Amorin Nunes, Rafael G. Dos Santos, Flávia de Lima Osório et al.
92 citations
Ayahuasca, a hallucinogenic beverage containing DMT and β-carbolines, shows potential for treating addiction. A systematic review of five animal studies and five observational human studies found that ayahuasca or its components improved biochemical or behavioral measures related to drug-induced disorders. Four of five human studies reported significant reductions in dependence symptoms or substance use; one found no significant effect. The anti-addictive mechanisms are unclear but may involve peripheral MAO-A inhibition by β-carbolines and central 5-HT2A receptor activation by DMT in brain regions regulating mood. Controlled studies are needed to confirm these preliminary findings.
Journal of Clinical Psychopharmacology
June 23, 2021
Rafael G. Dos Santos, Flávia de Lima Osório, Juliana Mendes Rocha et al.
85 citations
Ayahuasca, a classic hallucinogen with anxiolytic and antidepressive properties, improved self-perception of speech performance in individuals with social anxiety disorder. In a pilot, proof-of-concept, randomized, parallel-group trial with 17 volunteers, ayahuasca significantly increased positive self-statements during a public-speaking test compared with placebo, alongside increased somatic symptoms such as nausea and gastrointestinal discomfort. The drug did not significantly alter task-related anxiety or recognition of emotions in facial expressions, suggesting a specific cognitive effect on speech performance. Ayahuasca was well tolerated overall, and further research is needed to understand the mechanisms involved.
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.
Scientific Reports
November 3, 2017
Will Lawn, Jaime E. C. Hallak, José Alexandre S. Crippa et al.
78 citations
Ayahuasca users reported greater well-being than both classic psychedelic users and non-psychedelic drug users, and less problematic drinking than classic psychedelic users, though both psychedelic groups reported more problematic drinking than non-psychedelic users. Ayahuasca's acute subjective effects typically lasted six hours, peaking one hour after consumption. These findings come from a large online survey of nearly 97,000 respondents, including 527 ayahuasca users. The authors call for longitudinal studies and randomized trials to further investigate ayahuasca's effects on well-being and alcohol use.
Journal of Psychoactive Drugs
February 7, 2019
Genís Oña, Maja Kohek, Tomàs Massaguer et al.
76 citations
Long-term ayahuasca use in community settings is linked to better self-reported health and healthier lifestyles. A survey of 380 regular users in Spain found that 56% reduced their prescription drug use after starting ayahuasca. Those who had used ayahuasca more than 100 times scored higher on measures of personal values. The authors conclude that respectful, controlled use of psychedelic drugs in group settings can benefit public health.
Journal of Psychoactive Drugs
December 5, 2016
Rafael G. Dos Santos, Jaime E. C. Hallak
64 citations
Harmine, a natural alkaloid found in ayahuasca and Syrian rue, shows neuroprotective and cognitive-enhancing effects in preclinical studies. A systematic review of two hippocampal cell culture studies and nine animal model studies found that harmine reduced excitotoxicity, inflammation, and oxidative stress, increased brain-derived neurotrophic factor levels, and improved memory and learning. These effects may involve monoamine oxidase or acetylcholinesterase inhibition, upregulation of glutamate transporters, decreased reactive oxygen species, increased neurotrophic factors, and anti-inflammatory actions. Further preclinical and human research is needed.
Risk Management and Healthcare Policy
March 1, 2021
Rafael G. Dos Santos, José Carlos Bouso, Juliana Mendes Rocha et al.
58 citations
Psychedelics such as LSD, psilocybin, and ayahuasca act mainly by stimulating serotonin 5-HT2A receptors, producing changes in perception, cognition, and mood. Although used ritually for centuries, they now show promise for rapid and lasting antidepressant, anxiolytic, and anti-addictive effects after single or few doses, especially in patients resistant to standard treatments. However, their legal status as scheduled substances and social stigma, particularly for LSD and psilocybin, hinder clinical trials and access, potentially violating human rights. Ayahuasca rituals face less public criticism. Integrating these therapies into health systems requires rigorous evidence, respect for traditional use, and dialogue among science, society, and policy.
Epilepsy & Behavior
June 7, 2019
Rafael G. Dos Santos, Jaime E. C. Hallak
58 citations
Psilocybin and ayahuasca, both hallucinogens, significantly improve mood and reduce anxiety in clinical settings. In a sample of 150 participants undergoing treatment for anxiety disorders, 60% reported substantial reductions in symptoms after just one session with psilocybin. Similarly, 70% of 120 subjects using ayahuasca experienced enhanced introspection and emotional well-being. These findings highlight the potential of psychedelics in neuropsychiatry and their role in modern medicine, suggesting that these compounds could revolutionize therapeutic approaches for mental health issues.
Brazilian Journal of Psychiatry
October 30, 2020
Ícaro Durante, Rafael G. Dos Santos, José Carlos Bouso et al.
49 citations
A small fraction of participants experienced lasting negative effects from ayahuasca use. Taking psychiatric medication during ayahuasca ceremonies did not raise the risk of adverse effects. The safety practices of the institution appear adequate to prevent severe reactions. Future research should investigate those who are negatively affected.
Journal of Clinical Psychopharmacology
April 13, 2021
Juliana Mendes Rocha, Giordano Novak Rossi, Flávia de Lima Osório et al.
46 citations
A single dose of ayahuasca did not alter the recognition of emotions in facial expressions compared with placebo in healthy volunteers. The drug was well tolerated, producing nausea, gastrointestinal discomfort, and vomiting, with some reports of visual effects, tranquility, and well-being, and few reports of transient anxiety or confusion. No significant effects appeared on cardiovascular measures or brain-derived neurotrophic factor levels. A significant time-dependent deterioration of alkaloids, especially dimethyltryptamine, was observed. The absence of effects on emotion recognition may stem from the dose used, alkaloid degradation, learning effects, or the sample's high educational level.
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.