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.
PLoS ONE
February 18, 2015
Fernanda Palhano-Fontes, Kátia C. Andrade, Luís Fernando Tófoli et al.
461 citations
Ayahuasca, a psychedelic brew used traditionally by Amazonian Amerindians, significantly reduces activity in key hubs of the Default Mode Network (DMN), specifically the Posterior Cingulate Cortex (PCC)/Precuneus and medial Prefrontal Cortex (mPFC), as measured by fMRI in ten experienced subjects. Functional connectivity within the PCC/Precuneus also decreased after intake, while the orthogonality between the DMN and task-positive network showed no significant change. These findings suggest that the altered state of consciousness induced by Ayahuasca, similar to effects from psilocybin, meditation, and sleep, involves modulation of DMN activity and connectivity.
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.
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
Ayahuasca, a psychedelic brew, alters brain chemistry and connectivity in ways that may explain its lasting psychological effects. The findings point to glutamate neurotransmission playing a role in how psychedelics work in humans. Neurometabolic changes in the posterior cingulate cortex, a hub of the default mode network, along with increased connectivity between the anterior cingulate cortex and medial temporal lobe structures involved in emotion and memory, likely underlie the post-acute psychological effects of ayahuasca.
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.
Scientific Reports
August 1, 2017
Aline Viol, Fernanda Palhano-Fontes, Heloisa Onias et al.
154 citations
The entropic brain hypothesis suggests that psychedelic experiences arise from increased randomness in the brain's functional connectivity. Analyzing resting-state fMRI data from human subjects before and after ingesting ayahuasca, a psychedelic beverage used in Amazonian religious and scientific contexts, researchers found that the Shannon entropy of the brain's degree distribution increased, indicating greater disorder in network connections. Local integration within brain networks increased while global integration decreased. These findings align with the entropic brain hypothesis and relate to users' reports of 'mind-expansion.'
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.
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.
Science Advances
June 14, 2023
Leor Roseman, Christopher Timmermann, Daniel Golkowski et al.
65 citations
The effects of mind-altering drugs on brain function arise from complex interactions with multiple neurotransmitter systems, not just one. By linking the distribution of 19 neurotransmitter receptors and transporters (measured with PET) to changes in functional connectivity (measured with fMRI) caused by 10 drugs—anesthetics (propofol, sevoflurane, ketamine), psychedelics (LSD, psilocybin, DMT, ayahuasca), and others (MDMA, modafinil, methylphenidate)—the work shows a many-to-many mapping between drug effects and neurotransmitter systems. The drugs' impacts follow hierarchical gradients of brain structure and function, and regional susceptibility to drug-induced changes mirrors susceptibility to structural alterations from brain disorders.
Brazilian Journal of Psychiatry
November 21, 2018
Flávia S. Da Silva, Erick Allan Dos Santos Silva, Geovan Menezes de Sousa et al.
46 citations
Ayahuasca shows promise as an antidepressant, and these findings support its validation for treating mood disorders, including early-onset depression in adolescents. The results encourage further research into psychedelic drugs as therapeutic tools for mood disorders.
Journal of Psychopharmacology
February 1, 2022
Isabel Wießner, Marcelo Falchi-Carvalho, Lucas Oliveira Maia et al.
43 citations
A randomized, double-blind, placebo-controlled crossover study gave 24 healthy volunteers 50 micrograms of LSD or an inactive placebo and tested creativity near the drug's peak using multiple tasks. LSD changed creativity in three ways: it increased novelty, surprise, originality, and semantic distances (pattern break); decreased utility, convergent thinking, and marginally elaboration (disorganization); and increased symbolic thinking and ambiguity (meaning). The findings suggest LSD shifts cognitive resources away from normal patterns toward new ones, and that LSD-induced symbolic thinking might aid psychedelic-assisted therapy.
Entropy
January 30, 2019
Aline Viol, Fernanda Palhano-Fontes, Heloisa Onias et al.
37 citations
A new network metric, geodesic entropy, measures the Shannon entropy of distances from one node to all others in a network, characterizing how much influence a node has based on the overall network structure. Applied to resting-state functional brain networks of humans, the metric differentiates ordinary consciousness from the altered state induced by Ayahuasca ingestion. On average, functional networks from subjects in the altered state show larger geodesic entropy than those in the ordinary state, suggesting the metric can reveal differences in brain network organization across states of consciousness.
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.
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.
bioRxiv (Cold Spring Harbor Laboratory)
December 6, 2019
Felipe Augusto Cini da Silva, Isis M. Ornelas, Encarni Marcos et al.
9 citations
preprint
A single dose of d-LSD, a potent serotonergic agonist, increased preference for novel objects in young and adult rats several days after treatment, but did not increase preference in old animals unless followed by a 6-day exposure to enriched environment, which rescued novelty preference to young levels. Mass spectrometry-based proteomics in human brain organoids treated with d-LSD showed upregulation of proteins from the presynaptic active zone. A computational model of synaptic connectivity in the hippocampus and prefrontal cortex suggests that d-LSD enhances novelty preference by combining local synaptic changes in mnemonic and executive regions with alterations of long-range synapses, and that better pattern separation within enriched environment explains its synergy with d-LSD in rescuing novelty preference in old animals. These results advance the use of d-LSD in cognitive enhancement.
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)
July 13, 2022
Andrea I. Luppi, Justine Y. Hansen, R. Adapa et al.
5 citations
preprint
Psychoactive drugs reshape brain function by engaging multiple neurotransmitter systems simultaneously. By mapping the distribution of 19 neurotransmitter receptors and transporters (via PET) and the connectivity changes caused by 10 drugs (anesthetics, psychedelics, and stimulants), the study shows that drug effects are organized along hierarchical gradients of brain structure and function. Additionally, brain regions susceptible to drug-induced changes are also vulnerable to structural alterations from brain disorders. These findings reveal systematic links between molecular neurochemistry and large-scale functional reorganization.
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.
Journal of Physics Complexity
March 1, 2023
Aline Viol, G. M. Viswanathan, Oleksandra Soldatkina et al.
4 citations
The physical basis of consciousness is a central open question in science. This work compares resting-state functional brain networks of individuals before and after ingesting the psychedelic brew Ayahuasca. Using a measure called pairwise information parity, which quantifies statistical symmetries between brain region connections across the entire network, the authors found an increase in average information parity under psychedelic influence. Notably, information parity between regions of the limbic system and frontal cortex was consistently higher for all individuals while under the influence. These findings suggest that the resemblance of statistical influences between pairs of brain region activities tends to increase under Ayahuasca, possibly as a mechanism to maintain network functional resilience.
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.
Brazilian Journal of Psychiatry
October 7, 2020
Rafael G. Dos Santos, Dráulio Barros de Araújo, Rafael Faria Sanches et al.
2 citations
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