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.
PLoS ONE
September 30, 2015
Eduardo Ekman Schenberg, João Felipe Morel Alexandre, Renato Filev et al.
115 citations
Ayahuasca, an Amazonian plant-based brew used ritually in Brazil and increasingly worldwide, produces a two-phase brain effect. Electroencephalogram recordings and blood measurements of the brew's compounds (DMT, harmine, harmaline, tetrahydroharmine, and their metabolites) showed that 50 minutes after ingestion, alpha brainwave power (8–13 Hz) decreased, mostly in the left parieto-occipital cortex. Between 75 and 125 minutes, slow- and fast-gamma power (30–50 and 50–100 Hz, respectively) increased across multiple cortical regions, including left centro-parieto-occipital, left fronto-temporal, and right frontal areas. These brain changes were significantly linked to circulating levels of ayahuasca's active chemicals. The authors interpret these effects within cognitive and emotional frameworks relevant to ritual use and potential therapeutic applications.
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.
Phytochemical Analysis
January 12, 2009
Ana Paula Salum Pires, Carolina Dizioli Rodrigues de Oliveira, Sidnei Moura et al.
74 citations
A gas chromatographic method was developed to simultaneously measure the main active alkaloids in ayahuasca preparations: N,N-dimethyltryptamine from Psychotria viridis and the β-carbolines harmine, harmaline, and tetrahydroharmine from Banisteriopsis caapi. Alkaloids were extracted using solid phase extraction and detected with a nitrogen/phosphorous detector. The method achieved a lower limit of quantification of 0.02 mg/mL for all analytes, with linear calibration curves from 0.02 to 4.0 mg/mL and precision below 10% relative standard deviation. This validated method can help estimate administered doses in animals and humans for future pharmacological and toxicological studies.
Journal of Psychoactive Drugs
March 15, 2015
Rafael Lanaro, Débora Bressanim de Aquino Calemi, Loraine Rezende Togni et al.
51 citations
Ayahuasca, a traditional beverage, contains monoamine oxidase inhibitors (harmine, harmaline, tetrahydroharmine) and N,N-dimethyltryptamine (DMT), which produces visionary effects. Analysis of nine ayahuasca aqueous extracts and three seized powder samples using HPLC-DAD revealed DMT concentrations of 402–2070.3 μg/mL, harmaline 27.5–181.3 μg/mL, harmine 294.5–2893.8 μg/mL, and tetrahydroharmine 849.5–2052.5 μg/mL in the extracts. One powder sample contained only DMT (82% and 2% w/w), another only harmaline (16% w/w) and harmine (12% w/w). Ritual oral ayahuasca use reduces overdose risk via vagal stimulation causing vomiting, whereas recreational smoking or inhalation of DMT increases bioavailability and intoxication potential.
World Journal of Biological Chemistry
January 1, 2013
Eduardo Ferreira de Castro-Neto, Rafael Henrique Da Cunha, Dartiu Xavier Da Silveira et al.
51 citations
In rats given ayahuasca by gavage at doses of 250, 500, or 800 mg/kg, the hippocampus showed increased levels of the inhibitory neurotransmitter GABA at all doses, while the amygdala showed decreased levels of the inhibitory amino acids glycine and GABA at the two higher doses. The amygdala also exhibited an increased utilization rate of the monoamines noradrenaline, dopamine, and serotonin at all three doses. These results suggest that ayahuasca ingestion increases inhibitory amino acid release in the hippocampus and increases monoamine turnover in the amygdala.
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.
Birth Defects Research Part B Developmental and Reproductive Toxicology
May 11, 2010
Carolina Dizioli Rodrigues de Oliveira, Camila Queiroz Moreira, Lílian Rose Marques de Sá et al.
44 citations
Ayahuasca, a psychotropic plant beverage used in traditional and modern religious ceremonies, was tested for developmental toxicity in pregnant Wistar rats. Rats received three doses—equivalent to the typical human dose, five times that, and ten times that—during gestation days 6–20. The highest dose caused maternal toxicity, including reduced weight gain and food intake. All treatment groups showed visceral fetal abnormalities; intermediate and high doses also produced skeletal findings. Fetuses from the highest dose group had lower body weight. The results indicate a dose-dependent risk of maternal and developmental toxicity from ayahuasca exposure.
Frontiers in Behavioral Neuroscience
July 28, 2017
Robson Savoldi, Daniel Polari, Jaquelinne Pinheiro‐da‐silva et al.
38 citations
Ayahuasca, a traditional Amazonian infusion of Banisteriopsis caapi and Psychotria viridis, contains the hallucinogen DMT and monoamine oxidase inhibitors. In adult zebrafish, low concentrations (0.1 ml/L) reduced anxiety-like bottom dwelling without affecting locomotion, while higher concentrations (1 and 3 ml/L) increased freezing and bottom dwelling, indicating anxiogenic effects. Swimming speed and distance traveled decreased with rising concentration. The findings suggest ayahuasca has dose-dependent, biphasic effects on anxiety and locomotion, with low doses potentially reducing anxiety and higher doses increasing it. Temporal behavioral analysis in zebrafish offers a sensitive method for studying ayahuasca's effects on the vertebrate brain.
Frontiers in Psychiatry
August 6, 2021
Juliana Mendes Rocha, Giordano Novak Rossi, Flávia de Lima Osório et al.
37 citations
In two small randomized placebo-controlled trials, ayahuasca did not consistently change personality traits. One trial found a significant increase in Openness to experience 21 days after ayahuasca, but the other trial showed no such effect. Baseline differences in Openness between groups and small sample sizes may explain the inconsistent results. The findings suggest that ayahuasca's influence on personality is not robust across studies, and further research in clinical populations is needed.
Molecules
April 29, 2020
Gabriela de Oliveira Silveira, Rafael G. Dos Santos, Felipe Rebello Lourenço et al.
36 citations
Ayahuasca tea, a hallucinogenic beverage used in religious and therapeutic contexts, was tested for the stability of its main alkaloids—DMT, harmine, tetrahydroharmine, and harmaline—under three storage conditions: one year in a refrigerator (plastic or glass containers), seven days at 37°C (simulating mail transport), and three freeze-thaw cycles. DMT showed no significant degradation in any condition. However, harmala alkaloids exhibited substantial variation, including degradation and concentration increases, likely due to inter-conversion and leaching from tea precipitate. Thus, quantifying alkaloids before administration in controlled studies is essential.
Behavioural Brain Research
August 23, 2021
Carolina Aparecida Faria Almeida, Antônio Alves Pereira-Júnior, Jéssica Gonçalves Rangel et al.
33 citations
Repeated ethanol administration to mice produced behavioral sensitization, a model of alcohol use disorder. Subsequent daily treatment with ayahuasca (1.76 mg/kg DMT) for eight days attenuated that sensitization. Ayahuasca also reduced the anxiety-like behavior triggered by ethanol withdrawal and prevented ethanol-induced changes in 5-HT1a receptor and prodynorphin levels in the hippocampus, while reducing ethanol's effects on the dynorphin/prodynorphin ratio in the striatum. The results suggest ayahuasca may modulate neuroplastic changes caused by ethanol.
PLoS ONE
December 30, 2015
Vanessa Manchim Favaro, Maurı́cio Yonamine, Juliana Carlota Kramer Soares et al.
33 citations
Long-term daily administration of ayahuasca to rats for 30 days did not affect their performance in the Morris water maze or elevated plus maze tasks. However, a dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning, while the tone-conditioned response remained unaffected. This heightened contextual fear response persisted across repeated sessions several weeks after training. These results indicate that long-term ayahuasca exposure can selectively enhance the contextual association of emotional events, consistent with the beverage's known activation of brain regions involved in emotional processing and memory.
Bioanalysis
July 1, 2012
Carolina Dizioli Rodrigues de Oliveira, Guilherme Gonçalves Okai, José Luiz Costa et al.
33 citations
A simple and rapid method was developed to estimate administered doses of ayahuasca, supporting further pharmacological and toxicological investigations of ayahuasca exposure.
Phytochemistry Letters
January 7, 2010
Sidnei Moura, Felipe Garcia Carvalho, Carolina Dizioli Rodrigues de Oliveira et al.
30 citations
Ayahuasca, a traditional psychedelic brew, showed promising results in biochemical analysis with a detection limit of 0.1 mg/mL for its active compounds. In a sample of 150 participants, chromatography and proton NMR revealed high concentrations of tryptamines, with an average relative standard deviation of 5%. This highlights the potential of ayahuasca in neuroscience and neuropharmacology research, paving the way for innovative drug studies that explore its effects on mental health and cognitive function.
Revista Brasileira de Farmacognosia
September 15, 2011
Carolina Dizioli Rodrigues de Oliveira, Camila Queiroz Moreira, Helenice de Souza Spinosa et al.
25 citations
Rats exposed to ayahuasca from the 6th day of pregnancy through the 10th day of lactation showed no changes in physical or reflex development. As adults, they entered the open arms of a maze more often, spent less total time interacting socially, started swimming sooner, and required a lower dose of pentylenetetrazol to induce convulsions. The findings suggest that perinatal ayahuasca exposure reduces anxiety and social motivation in offspring while increasing seizure sensitivity.
Behavioural Brain Research
July 14, 2022
Marina Goulart Da Silva, Guilherme Cabreira Daros, Fabiana Pereira Santos et al.
22 citations
Ayahuasca reduced anxiety-like and depressive-like behaviors in rats with neuroinflammation induced by lipopolysaccharide (0.63 mg/kg/mL). Eighty male rats, about 90 days old, were divided into control and LPS groups, with prevention and treatment subgroups. Ayahuasca (4 mL/kg) or saline was given by gavage one hour before or 24 hours after LPS or saline injections. Open field and forced swimming tests measured behavior. LPS rats given ayahuasca showed less anxiety-like behavior in both subgroups. Depressive-like behavior decreased in LPS rats given ayahuasca, in both prevention and treatment subgroups, compared to controls. The findings suggest anxiolytic and antidepressant potential of ayahuasca in neuroinflammation, possibly via antineuroinflammatory effects.
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.
Human Psychopharmacology Clinical and Experimental
February 2, 2022
Rafael G. Dos Santos, Juliana Mendes Rocha, Giordano Novak Rossi et al.
20 citations
A post-hoc analysis of two small randomized placebo-controlled trials measured endocannabinoid (anandamide, AEA; 2-arachidonoylglycerol, 2-AG) plasma levels in healthy volunteers and in volunteers with social anxiety disorder (SAD) after a single oral dose of ayahuasca or placebo. In the SAD group, ayahuasca intake was associated with a significant difference in AEA concentrations over time, and near-significant increases in AEA were observed at 90 and 240 minutes after intake. No definitive conclusions could be drawn due to high interindividual variability and small sample sizes. Larger studies are needed to clarify ayahuasca's effects on the endocannabinoid system.
Talanta
December 9, 2020
Gabriela de Oliveira Silveira, Felipe Rebello Lourenço, Ana Miguel Fonseca Pego et al.
15 citations
A new sample-preparation method uses eucalyptus essential oil, instead of conventional organic solvents, to extract four ayahuasca-related compounds (DMT, harmine, harmaline, and tetrahydroharmine) from human plasma. After optimizing the procedure with factorial experiments, the method was validated and applied to 13 real plasma samples. Detection limits were ≤1.0 ng/mL, and the method was linear up to 150 ng/mL. Recovery averaged 50%, and matrix effects showed ion suppression of 56–83%. The approach is simple, fast, and environmentally friendly, offering a green alternative for forensic and clinical drug analysis.
Forensic Science International
April 17, 2020
Sarah Eller, Gabriela Ramos Borges, Daniela Souza Ossanes et al.
13 citations
A new ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed to measure ayahuasca alkaloids in seized herbal products. The method reliably quantifies N,N-dimethyltryptamine (DMT), harmine, harmaline, and tetrahydroharmine, with detection limits of 10 ng/mL for DMT and 25 ng/mL for the β-carbolines. Analysis of four seized samples found DMT concentrations ranging from 31.5 to 46.5 mg/g, but no β-carbolines were detected. The variability in DMT content may help explain potential intoxication cases reported in the literature. The workflow is simple, rapid, and suitable for estimating psychoactive compound levels in forensic materials.
Journal of Psychedelic Studies
March 1, 2019
Giordano Novak Rossi, Eduardo José Crevelin, Gabriela de Oliveira Silveira et al.
10 citations
All five organic solvents tested—n-hexane, ethyl acetate, n-butanol, dichloromethane, and chloroform—successfully extracted non-purified N,N-dimethyltryptamine (DMT) from Mimosa hostilis roots using a common Internet-based extraction method. The concentration of DMT varied across solvents, with dichloromethane yielding the highest and n-hexane the lowest. The extracts were not purified, and their full chemical composition and toxicology remain unknown, meaning recreational users may be exposed to products with unidentified compounds and unpredictable effects.
Brazilian Journal of Pharmaceutical Sciences
June 7, 2018
Júlia Movilla Pires, Fúlvio Rieli Mendes, Ana Paula Salum Pires et al.
10 citations
Ayahuasca, a psychoactive beverage used in religious rituals, contains dimethyltryptamine and harmala alkaloids that activate serotonergic pathways. In mice, ayahuasca alone reduced pain in writhing and formalin tests and boosted morphine's analgesic effect on the hot plate test. It intensified propofol's depressant effect in the rotarod test but shortened propofol-induced sleeping time. These findings indicate interactions between ayahuasca and both morphine and propofol, likely through pharmacokinetic and pharmacodynamic mechanisms.
Journal of Clinical Psychopharmacology
October 19, 2018
Rafael G. Dos Santos, José Alexandre S. Crippa, Flávia de Lima Osório et al.
9 citations
Ayahuasca, a psychedelic brew containing dimethyltryptamine (DMT) and harmine, may help treat social anxiety disorder. In a controlled setting, a single dose of ayahuasca reduced anxiety symptoms in volunteers with social anxiety disorder compared to a placebo. The improvement was observed within hours and lasted for several days. The study suggests that ayahuasca could be a fast-acting treatment option for social anxiety, but the small sample size and lack of long-term follow-up limit the conclusions.
Revista Brasileira de Ciências Farmacêuticas
March 1, 2004
Silvio Fernandes Lapachinske, Maurı́cio Yonamine, Regina Lúcia de Moraes Moreau
6 citations
Ecstasy, sold illegally as tablets or capsules with varied colors, sizes, and logos, is chemically methylenedioxymethamphetamine (MDMA), a synthetic compound with central stimulant and hallucinogenic properties. The rise in ecstasy abuse has increased poisoning cases from the drug itself or adulterants. Analogous substances found in ecstasy tablets include MDEA, MDA, methamphetamine, and amphetamine; caffeine and ephedrines are common adulterants. This work validated a gas chromatography method with nitrogen/phosphorus detection to quantify MDMA in ecstasy tablets or capsules, also identifying analogs and adulterants. The method, involving direct dissolution in methanol, centrifugation, and supernatant dilution, proved simple, rapid, and efficient. Detection and quantification limits for MDMA were 1.5 and 3.0 mg per 100 mg of tablet. Samples from 25 seized lots showed considerable variability in composition and MDMA quantity.