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INTRODUCTION: Ayahuasca is a psychedelic brew originally used by Amazonian indigenous groups and in religious rituals. Pre-clinical and observational studies have demonstrated its possible potential as an antidepressant, and open- and placebo-controlled clinical trials corroborated these results. For it to become an approved treatment for depression, its safety and tolerability need to be assessed and documented. AREAS COVERED: We have gathered data regarding the occurrence of adverse events (AEs) in all reported randomized, placebo-controlled trials with healthy and clinical populations involving ayahuasca administration (n = 108 ayahuasca administrations). We systematically categorized these results, recorded their prevalence, and discussed the possible mechanisms related to their emergence. EXPERT OPINION: There were no reports of serious AEs, indicating a relative safety of ayahuasca administration in controlled settings. Most common AEs included nausea, vomiting, headaches, and transient increases in cardiovascular measurements. Ayahuasca research is still in its infancy, especially concerning the absence of large and robust clinical trials to verify its antidepressant effects. Dose standardization, legal prohibition of the possession of its alkaloids and how traditional communities will be compensated if ayahuasca becomes an approved medicine are the biggest obstacles to overcome for its future use in the therapeutic context.

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Abstract Ayahuasca (AYA) is a psychedelic beverage with therapeutic potential for many mood and anxiety disorders. Although there are some preclinical studies, no published reports have tested the behavioral effects of AYA gavage in animal models. This investigation aimed to characterize the behavior of Wistar rats after acute ingestion of AYA for 40 min in the open field test (OFT). The sample consisted of three experimental groups treated with different dosages of AYA (125, 250, or 500 mg kg-1) and a control group. Each group consisted of 10 participants. After gavage, the number of crossings of the OFT grid lines, latency to enter the central area of the device, grooming frequency, and time spent in the central perimeter of the device were immediately evaluated. Analyses were based on one-way ANOVA and a linear-regression mixture model for longitudinal data. AYA intake did not interfere with habituation. The 500 mg kg-1 group showed a decrease in the time spent in the center of the device and in the number of crossings compared to the control group in the last 10 min. These results suggest that gavage with AYA did not interfere with the results, and the behavioral effects were perceived only between 30 and 40 min after gavage. Taken together, the results indicate that three aspects should be considered in OFT studies of AYA acute effects: the moment when the observation starts, the observation period, and the AYA dosage.

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Ayahuasca is a beverage obtained from decoctions of the liana Banisteriopsis caapi plus the shrub Psychotria viridis. This beverage contains a combination of monoamine oxidase inhibitors (harmine, harmaline, and tetrahydroharmine) and N,N-dimethyltryptamine, the main substance responsible for its visionary effect. The ritualistic use of ayahuasca is becoming a global phenomenon. Most members of ayahuasca churches consume this beverage throughout their life, and many reports have discussed the therapeutic potential of this beverage. Ayahuasca is consumed orally, and the liver, as the major organ for the metabolism and detoxification of xenobiotics absorbed from the alimentary tract, may be susceptible to injury by compounds present in the ayahuasca decoction. In this study, we evaluated biochemical parameters related to hepatic damage in the serum of 22 volunteers who consumed ayahuasca twice a month or more for at least one year. There was no significant alteration in the following parameters: alanine aminotransferase, aspartate aminotransferase, bilirubin, creatinine, urea, lactate dehydrogenase, alkaline phosphatase, and gamma glutamyl transferase. These findings indicate that chronic ayahuasca consumption in a religious context apparently does not affect hepatic function.

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Alucinógenos (ALU) são substâncias psicoativas que não induzem o indivíduo à dependência, possuem perfil de segurança de uso mais alto quando comparado a outras drogas e baixa capacidade de causar tolerância ao uso. Estudos recentes propõem o uso de ALU como tratamento a algumas doenças e transtornos relacionados ao sistema nervoso central, como a depressão, ansiedade e dependência. Dentre os ALU, a ayahuasca (AYA), cujo princípio ativo é a dimetiltriptamina (DMT), é uma bebida psicoativa amplamente utilizada pelas populações indígenas em rituais religiosos. Existem evidências de que pode ser eficaz no tratamento de dependência relacionada ao álcool e nicotina. No entanto, para a cocaína, a segunda droga ilícita mais utilizada no Brasil e na Europa, não existem muitos estudos. O objetivo deste trabalho foi avaliar o potencial da AYA em prevenir a expressão da sensibilização comportamental (SC) induzida pela cocaína e as repercussões neuroquímicas do tratamento em camundongos C57Bl/6. Para tanto, foi avaliada a influência da administração aguda de AYA (1,76; 3,0; 17,6; 30,0 mg/kg de DMT v.o.) na atividade locomotora dos animais em campo aberto (CA). Como não houve diferença estatística na distância percorrida durante a análise, as duas menores doses (1,76 e 3,0 mg/kg de DMT v.o.) foram escolhidas como doses iniciais para a realização do protocolo de prevenção à expressão da SC induzida pela cocaína. Inicialmente, os animais foram habituados no CA durante 3 dias consecutivos após a administração de solução salina 0,9% i.p. No 4o dia experimental, os animais receberam, durante 10 dias alternados, cocaína 10 mg/kg ou salina 0,9% i.p. e foram submetidos diretamente à avaliação da atividade locomotora no CA por 30 minutos. Vinte e quatro horas depois, receberam, durante 8 dias consecutivos, água ou AYA (1,76 ou 3,0 mg/kg de DMT v.o.) e após 30 minutos da administração, foram colocados no CA por 30 minutos para análise da atividade locomotora. No dia seguinte, os camundongos foram desafiados com uma administração de salina. E, no último dia experimental, foi realizado um desafio com cocaína, sempre colocando o animal no CA por 30 minutos. Nessas doses, a AYA não foi eficaz em prevenir a expressão da SC induzida pela cocaína. Dessa forma, avaliamos doses superiores de AYA (15, 30 e 45 mg/kg de DMT v.o.), as quais foram capazes de prevenir a expressão da SC à cocaína. Assim, o protocolo experimental foi novamente realizado com a menor dose (15 mg/kg de DMT v.o.), ao término do protocolo experimental, os animais foram eutanasiados e tiveram seu córtex pré-frontal, estriado e hipocampo dissecados para análise por immunoblotting dos receptores serotoninérgicos 5-HT1A e 5-HT2A. No entanto, não foram não observadas diferenças significativas ao comparar o nível proteico dos receptores nos grupos experimentais. Dessa forma, esses resultados sugerem que a AYA pode ser uma boa estratégia terapêutica para a dependência em cocaína, abrindo caminho para novos estudos

Psychedelics (PSY) are psychoactive substances that do not induce the individual to addiction, have a higher use safety profile when compared to other drugs and low ability to cause tolerance to use. Recent studies propose the use of PSY as a treatment for some diseases and disorders related to the central nervous system, such as depression, anxiety and addiction. Among the PSY, ayahuasca (AYA), whose active component is dimethyltryptamine (DMT), is a psychoactive drink widely used by indigenous populations in religious rituals. There is evidence that it may be effective in treating alcohol and nicotine addiction. However, for cocaine, the second most widely used illicit drug in Brazil and Europe, there are not many studies. The aim of this study was to evaluate the potential of AYA in preventing cocaine-induced behavioral sensitization (BS) expression and the neurochemical repercussions of this treatment in C57Bl/6 mice. Thus, we evaluated the influence of acute administration of AYA (1.76; 3.0; 17.6; 30.0 mg/kg of DMT, orally) on the locomotor activity of animals in the open field (OF). As there was no statistical difference in the distance travelled during the analysis, the two lowest doses (1.76 and 3.0 mg/kg of DMT, orally) were chosen as initial doses to perform the cocaine-induced expression prevention protocol. First, animals were habituated to OF for 3 consecutive days following administration of saline 0.9% i.p. On the fourth experimental day, the animals received for 10 alternate days cocaine 10 mg/kg or saline 0,9% i.p. and were directly submitted to the evaluation of locomotor activity in OF for 30 minutes. Twenty-four hours later they received, for 8 consecutive days, water or AYA (1.76 or 3.0 mg/kg of DMT, orally), and 30 minutes after administration, they were placed in the OF for 30 minutes for analysis of locomotor activity. The next day, the mice were challenged with saline administration. On the last experimental day, a cocaine challenge was performed, always placing the animal in the OF for 30 minutes. At these doses, AYA was not effective in preventing cocaine-induced expression of BS. Thus, we evaluated higher doses of AYA (15, 30 and 45 mg/kg of DMT, orally), which were able to prevent the expression of cocaine-induced BS. Thus, the experimental protocol was again performed with the lowest dose (15 mg/kg of DMT, orally). At the end of the experimental protocol, the animals were euthanized and their prefrontal cortex, striatum and hippocampus were dissected for serotonergic receptor 5-HT1A and 5-HT2A by immunoblotting. However, no significant differences were observed when comparing receptor protein level in the experimental groups. Thus, these results suggest that AYA may be a good therapeutic strategy for cocaine addiction, paving the way for further studies

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Background Ayahuasca is a botanical hallucinogenic preparation traditionally used by indigenous populations of Northwestern Amazonian countries for ritual and therapeutic purposes. It is rich in β-carboline alkaloids and N,N-dimethyltryptamine (DMT). Preclinical, observational, and experimental studies suggest that ayahuasca and its alkaloids have anxiolytic and antidepressive effects. We recently reported in an open-label trial that ayahuasca administration was associated with significant decreases in depression symptoms for 2-3 weeks after the experimental session in 17 patients with treatment-resistant major depressive disorder. Objectives To investigate if the experiment had any long-lasting effects on patients Methods Eight patients were interviewed 4 to 7 years after ayahuasca intake. Results Our results suggest that ayahuasca was well tolerated and that symptom reductions were limited to a few weeks. Importantly, most patients believed that the experience was among the most important of their lives, even 4-7 years later. Discussion To the best of our knowledge, this is the first long-term follow-up of a clinical sample that participated in an ayahuasca trial. Further studies with different and repeated dosing should be designed to further explore the antidepressive and anxiolytic effects of ayahuasca.

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ABSTRACT Ayahuasca is a beverage with psychoactive properties used in religious and ceremonial rituals by some religious groups. The main active components of ayahuasca are dimethyltryptamine and the harmala alkaloids with ß-carboline structure acting as monoamine oxidase A inhibitors. This combination produces a pronounced activation of serotonergic pathways and presents potential interaction with other psychotropics. The objective of this study was to investigate the possible interactions between ayahuasca and agents employed in general anesthesia. The pharmacological interactions between ayahuasca and morphine or propofol were evaluated in mice using doses of 12, 120 and 1200 mg/kg (0.1 to 10 times the average dose consumed by humans in religious rituals). Ayahuasca alone showed an antinociceptive effect in the writhing and formalin tests, and intensified the analgesic effect of morphine in the hot plate test. Concerning the pharmacological interactions between ayahuasca and propofol, the results were opposite; ayahuasca intensified the depressant effect of propofol in the rotarod test, but decreased the sleeping time induced by propofol. These set of results showed the occurrence of some interactions between ayahuasca and the drugs morphine and propofol, possibly by both pharmacokinetics and pharmacodynamics mechanisms

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The aim of this study was to evaluate the antimicrobial activity in vitro of ethanolic extracts of Banisteriopsis anisandra. Tests were performed using the extracts overlay method in the culture medium for phytopathogenic fungi Rhizoctonia solani and Fusarium oxysporum, and disk diffusion for the microorganisms Staphylococcus aureus and Candida albicans. Ethanolic extracts from leaves were prepared by maceration (extract I) and decoction (extract II) at 430.0, 215.0 and 107.5 mg/mL. The growth inhibition of R. solani and F. oxysporum was determined by calculating the mycelia growth speed rate (MGSR) and, in relation C. albicans and S. aureus, it was determined by measuring the inhibition halos. Extracts that caused significant inhibition were also tested at 86.0, 64.5, 43.0 and 21.5 mg/mL for C. albicans and S. aureus. Both extracts showed inhibitory activity on the microorganisms studied. Rizoctonia solani showed lower MGSR in the presence of extract II (107.5 mg/mL) and Fusarium oxysporum showed slight MGSR reduction in the presence of extract I (107.5 mg/mL) and II (107.5 and 215 mg/mL). Ethanolic extracts I and II inhibited the growth of C. albicans, with the highest rates of inhibition observed in the presence of extract II (215.0 mg/mL). For S. aureus, the highest inhibitory activity was observed in the presence of ethanolic extract II, prepared by decoction at 430.0 mg/mL. Results showed a promising antimicrobial activity of extracts of B. anisandra, which may contribute to further studies leading to a future development of medicines to treat human and plant diseases caused by these organisms.

O objetivo deste estudo foi avaliar a atividade antimicrobiana in vitro de extratos etanólicos de Banisteriopsis anisandra. Os testes foram realizados utilizando o método de sobreposição de extratos em meio de cultura para fungos fitopatogênicos Rhizoctonia solani e Fusarium oxysporum e de difusão em disco para os microrganismos Staphylococcus aureus e Candida albicans. Foram testados de extratos etanólicos de folhas preparados por maceração (extrato I) e decocção (extrato II), nas concentrações de 430,0; 215,0 e 107,5 mg/mL. A inibição do crescimento de R. solani e F. oxysporum foi determinada pelo cálculo do índice de velocidade de crescimento micelial (IVCM) e de C. albicans e S. aureus, por meio da medida da halos de inibição. Os extratos que causaram inibição significativa também foram testados nas concentrações de 86,0; 64,5; 43,0 e 21,5 mg/mL para C. albicans e S. aureus. Ambos os extratos mostraram atividade inibitória sobre os microrganismos estudados. Rizoctonia solani apresentou menor IVCM na presença do extrato II (107,5 mg/mL) e Fusarium oxysporum apresentou discreta redução no IVCM na presença do extrato I (107,5 mg/mL) e II (107,5 e 215 mg/mL). Extratos etanólicos I e II inibiram o crescimento de C. albicans, com as maiores taxas de inibição observadas na presença do extrato II (215,0 mg/mL). Para S. aureus a maior atividade inibitória foi observada na presença do extrato II, na concentração de 430 mg/mL. Os resultados mostraram promissora atividade antimicrobiana de extratos de B. anisandra, o que pode contribuir para estudos futuros visando o desenvolvimento de medicamentos para doenças humanas e de plantas causadas por estes microrganismos.

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Ayahuasca is an Amazonian psychoactive plant beverage containing the serotonergic 5-HT(2A) agonist N,N-dimethyltryptamine (DMT) and monoamine oxidase-inhibiting alkaloids (harmine, harmaline and tetrahydroharmine) that render it orally active. Ayahuasca ingestion is a central feature in several Brazilian syncretic churches that have expanded their activities to urban Brazil, Europe and North America. Members of these groups typically ingest ayahuasca at least twice per month. Prior research has shown that acute ayahuasca increases blood flow in prefrontal and temporal brain regions and that it elicits intense modifications in thought processes, perception and emotion. However, regular ayahuasca use does not seem to induce the pattern of addiction-related problems that characterize drugs of abuse. To study the impact of repeated ayahuasca use on general psychological well-being, mental health and cognition, here we assessed personality, psychopathology, life attitudes and neuropsychological performance in regular ayahuasca users (n = 127) and controls (n = 115) at baseline and 1 year later. Controls were actively participating in non-ayahuasca religions. Users showed higher Reward Dependence and Self-Transcendence and lower Harm Avoidance and Self-Directedness. They scored significantly lower on all psychopathology measures, showed better performance on the Stroop test, the Wisconsin Card Sorting Test and the Letter-Number Sequencing task from the WAIS-III, and better scores on the Frontal Systems Behavior Scale. Analysis of life attitudes showed higher scores on the Spiritual Orientation Inventory, the Purpose in Life Test and the Psychosocial Well-Being test. Despite the lower number of participants available at follow-up, overall differences with controls were maintained one year later. In conclusion, we found no evidence of psychological maladjustment, mental health deterioration or cognitive impairment in the ayahuasca-using group.

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