Ayahuasca, Personality and Acute Psychological Effects in Neo-Shamanic and Religious Settings in Uruguay.

This study is an interdisciplinary research into Uruguayan ayahuasca users belonging to one neo-shamanic and one Santo Daime group. The study involved the chemical analysis of ayahuasca samples, an ethnographic description of the two traditions and rituals, and the application of psychometric scales to measure personality differences, and the acute psychological effects during an ayahuasca ritual. Personality measurements showed lower scores for Santo Daime in Neuroticism-Anxiety, Dependence, Low Self-Esteem, Anger and Restlessness. These differences may be related to the presence of participants under treatment in the neo-shamanic group and/or to the protective effects of a church religion such as Santo Daime. Regarding acute effects, the neo-shamanic group showed higher scores in Somesthesia and Perception, which can be related to the high-arousal ritual setting. Chemical analysis for the ayahuasca samples showed a typical composition of alkaloids. No adulterants were found. The sample from the neo-shamanic group displayed a higher ß-carbolines:DMT ratio compared to the Santo Daime sample, which could be related to the higher effects observed for Somesthesia for the neo-shamanic group. Significant positive correlations between some personality traits and acute effects were found only in the neo-shamanic group, which may be related to the more individualistic approach of this tradition.

Ayahuasca Ritual, Personality and Sociality: Observational Research Conducted in a Substance Use Disorder Rehabilitation Center in Uruguay.

The current article presents a mixed qualitative-quantitative observational study of the effect of ayahuasca ritual on subjective experiences and personality traits on participants of a center specialized in the treatment of substance use disorder in Uruguay. When comparing the psychological traits of ayahuasca participants to a control group, quantitative results using the Zuckerman-Kuhlman-Aluja Personality Questionnaire showed statistically significant higher scores in Impulsive Sensation Seeking, Boredom Susceptibility, and Social Warmth scales. Qualitative analysis of ayahuasca experiences resulted in five main categories: emotional experiences (including social emotions such as love and empathy), corporal experiences, spiritual/transcendental experiences, personal experiences, and visions. Last, qualitative descriptions provide support for the importance of social interactions in the phenomenological manifestations of the psychedelic experience. Both quantitative and qualitative results suggest that the combination of social interactions and the pharmacological action of ayahuasca could facilitate the manifestation of social emotions during the ritual, and may contribute to the long-term increase of empathic and social aspects of personality.

Immunological Modulation and Control of Parasitaemia by Ayahuasca Compounds: Therapeutic Potential for Chagas's Disease.

Ayahuasca is a psychoactive and psychedelic decoct composed mainly of Banisteriopsis caapi and Psychotria viridis plant species. The beverage is rich in alkaloids and it is ritualistically used by several indigenous communities of South America as a natural medicine. There are also reports in the literature indicating the prophylaxis potential of Ayahuasca alkaloids against internal parasites. In the present study, Ayahuasca exhibited moderate in vitro activity against Trypanosoma cruzi trypomastigotes (IC50 95.78 µg/mL) compared to the reference drug benznidazole (IC50 2.03 µg/mL). The ß-carboline alkaloid harmine (HRE), isolated from B. caapi, was considered active against the trypomastigotes forms (IC50 6.37), and the tryptamine N, N-dimethyltryptamine (DMT), isolated from P. viridis was also moderately active with IC50 of 21.02 µg/mL. Regarding the in vivo evaluations, no collateral effects were observed. The HRE alone demonstrated the highest trypanocidal activity in a dose-responsive manner (10 and 100 mg/kg). The Ayahuasca and the association between HRE and DMT worsened the parasitaemia, suggesting a modulation of the immunological response during the T. cruzi infection, especially by increasing total Immunoglobulin (IgG) and IgG1 antibody levels. The in silico molecular docking revealed HRE binding with low energy at two sites of the Trypanothione reductase enzyme (TR), which are absent in humans, and thus considered a promissory target for drug discovery. In conclusion, Ayahuasca compounds seem to not be toxic at the concentrations of the in vivo evaluations and can promote trypanocidal effect in multi targets, including control of parasitaemia, immunological modulation and TR enzymatic inhibition, which might benefit the treatments of patients with Chagas' disease. Moreover, the present study also provides scientific information to support the prophylactic potential of Ayahuasca against internal parasites.

Evaluation of the In Vitro Wound-Healing Potential of Ayahuasca.

Ayahuasca is an Amazonian drink, which contains ß-carboline alkaloids and N,N-dimethyltryptamine. The aim of this study was to evaluate the healing potential of decoctions of a commercial mixture, four individual plants and four mixtures of two plants used in the ayahuasca preparation. Thus, the cytotoxic potential of the samples was evaluated and a wound-healing assay was performed with a NHDF cell line. Subsequently, a parallel artificial membrane permeability assay was also performed, to verify if any psychoactive compound could be absorbed by skin fibroblasts. The integrity and permeability of the cell layer were also evaluated, using the transepithelial electrical resistance assay and Lucifer yellow permeability assay, respectively. The compounds absorbed by the cell layer were quantified by high-performance liquid chromatography coupled to a diode array detector. The results showed that only one sample showed cytotoxicity and all the others promoted the migration of skin fibroblasts. Additionally, it was also verified that ß-carbolynic alkaloids and N,N-dimethyltriptamine were not absorbed by the cell layer, and in general, did not interfere with its permeability and integrity. To the best of our knowledge, this is the first study where ayahuasca's wound-healing potential was evaluated.

Components of Banisteriopsis caapi, a Plant Used in the Preparation of the Psychoactive Ayahuasca, Induce Anti-Inflammatory Effects in Microglial Cells.

Banisteriopsis caapi is used to prepare the psychoactive beverage ayahuasca, and both have therapeutic potential for the treatment of many central nervous system (CNS) conditions. This study aimed to isolate new bioactive compounds from B. caapi extract and evaluate their biological activity, and that of the known ß-carboline components of the plant (harmine, harmaline, and tetrahydroharmine), in BV-2 microglial cells, the in vivo activation of which is implicated in the physiopathology of CNS disorders. B. caapi extract was fractionated using semipreparative liquid chromatography (HPLC-DAD) and the exact masses ([M + H]+m/z) of the compounds in the 5 isolated fractions were determined by high-resolution LC-MS/MS: F1 (174.0918 and 233.1289), F2 (353.1722), F3 (304.3001), F4 (188.1081), and F5 (205.0785). Harmine (75.5-302 µM) significantly decreased cell viability after 2 h of treatment and increased the number of necrotic cells and production of reactive oxygen species at equal or lower concentrations after 24 h. F4 did not impact viability but was also cytotoxic after 24 h. Most treatments reduced proinflammatory cytokine production (IL-2, IL-6, IL-17, and/or TNF), especially harmaline and F5 at 2.5 µM and higher concentrations, tetrahydroharmine (9.3 µM and higher), and F5 (10.7 µM and higher). The results suggest that the compounds found in B. caapi extract have anti-inflammatory potential that could be explored for the development of treatments for neurodegenerative diseases.

Ayahuasca Lyophilization (Freeze-drying) Protocol with Pre- and Post-procedure Alkaloids Quantification.

Ayahuasca is a psychoactive brew from the decoction of different Amazonian plants, traditionally used in several cultures, religions, and rituals. Scientific studies with ayahuasca are rapidly increasing due to its subjective effects and therapeutic potential. Although ayahuasca is traditionally used in its liquid presentation, lyophilized (freeze-dried) ayahuasca is often used in scientific experimentation settings. However, there is no standard process or guideline to freeze-dry ayahuasca nor comparison of the chemical profile between the liquid and freeze-dried presentations. Therefore, we describe a reproducible five-day protocol for ayahuasca lyophilization with alkaloids quantification by liquid chromatography coupled to tandem mass spectrometry of both the liquid and the final freeze-dried ayahuasca. By the end of the protocol, approximately 295 g of freeze-dried extract with similar alkaloids concentration were obtained from two liters of ayahuasca (dry matter: 14.75 %). The final extract was stored for three years inside a vacuum desiccator (approximately 6°C) with its texture quality preserved. Further studies should address the impact of different storage conditions and the lyophilization on the alkaloids' quantity of the freeze-dried ayahuasca, especially the use of heat in regards to the ß-carbolines.

Beyond the Psychoactive Effects of Ayahuasca: Cultural and Pharmacological Relevance of Its Emetic and Purging Properties.

The herbal preparation ayahuasca has been an important part of ritual and healing practices, deployed to access invisible worlds in several indigenous groups in the Amazon basin and among mestizo populations of South America. The preparation is usually known to be composed of two main plants, Banisteriopsis caapi and Psychotria viridis, which produce both hallucinogenic and potent purging and emetic effects; currently, these are considered its major pharmacological activities. In recent decades, the psychoactive and visionary effect of ayahuasca has been highly sought after by the shamanic tourism community, which led to the popularization of ayahuasca use globally and to a cultural distancing from its traditional cosmological meanings, including that of purging and emesis. Further, the field of ethnobotany and ethnopharmacology has also produced relatively limited data linking the phytochemical diversity of ayahuasca with the different degrees of its purging and emetic versus psychoactive effects. Similarly, scientific interest has also principally addressed the psychological and mental health effects of ayahuasca, overlooking the cultural and pharmacological importance of the purging and emetic activity. The aim of this review is therefore to shed light on the understudied purging and emetic effect of ayahuasca herbal preparation. It firstly focuses on reviewing the cultural relevance of emesis and purging in the context of Amazonian traditions. Secondly, on the basis of the main known phytochemicals described in the ayahuasca formula, a comprehensive pharmacological evaluation of their emetic and purging properties is presented.

Teacher plants - Indigenous Peruvian-Amazonian dietary practices as a method for using psychoactives.

ETHNOPHARMACOLOGICAL RELEVANCE: Indigenous groups of the Amazon have developed intricate methods for the application of psychoactives, among which particularly the dieta or diet method of Peruvian-Amazonian traditional medicine stands out. It is a retreat-like intervention involving lengthy periods of social, behavioural, and alimentary restrictions, while ingesting specially prepared plant substances. The interplay of the dietary conditions and plants ingested sensitizes the dieter to receive healing, strength, guidance, and knowledge. From a clinical scientific point of view, the method has remained largely underexplored, but seems more pertinent than ever given the increasing interest in Amazonian psychoactive preparations including ayahuasca (Banisteriopsis caapi) and the burgeoning field of psychedelic-assisted therapies in general. AIM OF THE STUDY: This study offers a descriptive account and emic interpretation of the Peruvian-Amazonian dieta. More specifically we document in detail the procedure, its context and purpose of application, effects, modes of action, adverse effects, and risks, from the perspectives of a sample of Peruvian traditional healers. The Peruvian-Amazonian dieta is a multi-purpose method for making use of medicinal plants, many of which (but not all), are psychoactive; the current work especially focuses on its therapeutic applications in conjunction with psychoactives. METHODS: We interviewed 16 healers working in the Ucayali, San Martín, and Loreto provinces of Peru using a semi-structured interview approach. Interviews were audio-recorded and transcribed verbatim. The extensive data derived from these interviews were analysed by means of computer-assisted manifest qualitative content analysis using a theory-advancing approach. Over 500 coded text segments were categorized, resulting in 7 main theme clusters and corresponding sub-themes. RESULTS: The interviewed healers described a complex intervention with multifaceted applications (treatment, prevention, training) and effects in various domains (body, mind, spirit, energy). The process was portrayed as transformative, with benefits attributed to the effects of the so-called teacher plants in conjunction with the diet's conditions, along with the skill of the healer guiding the intervention. Further, a detailed risk assessment revealed sophisticated safety measures and tools designed to address adverse responses. The importance of adequate training of the healer that administers the diet was particularly highlighted in this context. CONCLUSIONS: The dieta is a central therapeutic concept and tool in Peruvian-Amazonian traditional medicine and a unique method for using psychoactive plants. Multidisciplinary health research that includes traditional treatment methods from Indigenous cultures, Amazonian and other, should not be neglected in the current global interest in psychedelic therapies; such research may in the long-term contribute to a more inclusive psychedelic research paradigm as well as healthcare practice in countries where rich traditional healing systems exist, and perhaps beyond. It may also contribute to the recognition of the Indigenous healers as not only historical forerunners, but also current leading experts in psychedelic medicine.

Effects of Ayahuasca on the Recognition of Facial Expressions of Emotions in Naive Healthy Volunteers: A Pilot, Proof-of-Concept, Randomized Controlled Trial.

BACKGROUND: The recognition of emotions in facial expressions (REFE) is a core aspect of social cognition. Previous studies with the serotonergic hallucinogens lysergic acid diethylamide and psilocybin showed that these drugs reduced the recognition of negative (fear) faces in healthy volunteers. This trial assessed the acute and prolonged effects of a single dose of ayahuasca on the REFE. METHODS: Twenty-two healthy volunteers participated in a pilot, proof-of-concept, randomized trial. Study variables included a REFE task performed before and 4 hours after drug intake, subjective effects (self-reports/observer impressions), tolerability measures (cardiovascular measures, self-reports), and brain-derived neurotrophic factor plasma levels. The REFE task was applied again 1, 7, 14, and 21 days and 3 months after drug intake. Stability of ayahuasca alkaloids during the study was also assessed (room temperature, 18 months). FINDINGS: Compared with placebo, ayahuasca did not modify the REFE. No significant effects were observed on cardiovascular measures and brain-derived neurotrophic factor levels. Volunteers reported visual effects, tranquility/relaxation, and well-being, with few reports of transient anxiety/confusion. Ayahuasca was well tolerated, producing mainly nausea, gastrointestinal discomfort, and vomiting. A significant time-dependent deterioration of alkaloids was observed, especially for dimethyltryptamine. CONCLUSIONS: Absence of significant effects on the REFE task could be due to lack of effects of ayahuasca (at the doses used), alkaloid degradation, learning effects, and the high educational level of the sample. Further trials with different samples are needed to better understand the effects of ayahuasca and other serotonergic hallucinogens on the REFE. Future trials should improve methods to guarantee the stability of ayahuasca alkaloids.

Examining changes in personality following shamanic ceremonial use of ayahuasca.

The present study examines the association between the ceremonial use of ayahuasca-a decoction combining the Banistereopsis caapi vine and N,N-Dimethyltryptamine-containing plants-and changes in personality traits as conceived by the Five-Factor model (FFM). We also examine the degree to which demographic characteristics, baseline personality, and acute post-ayahuasca experiences affect personality change. Participants recruited from three ayahuasca healing and spiritual centers in South and Central America (N = 256) completed self-report measures of personality at three timepoints (Baseline, Post, 3-month Follow-up). Informant-report measures of the FFM were also obtained (N = 110). Linear mixed models were used to examine changes in personality and the moderation of those changes by covariates. The most pronounced change was a reduction in Neuroticism dzself-reportT1-T2 = - 1.00; dzself-reportT1-T3 = - .85; dzinformant-reportT1-T3 = - .62), reflected in self- and informant-report data. Moderation of personality change by baseline personality, acute experiences, and purgative experiences was also observed.

Acute Psychological Adverse Reactions in First-Time Ritual Ayahuasca Users: A Prospective Case Series.

BACKGROUND: In recent decades, ritualistic use of ayahuasca has spread throughout the world. Retrospective studies have suggested a good psychological safety profile, but prospective studies involving ceremony ayahuasca-naive participants are lacking. METHODS: We conducted the study using a subsample from a previous study, for which first-time ceremony ayahuasca participants were recruited. The subsample consisted of 7 subjects who experienced acute and challenging psychological reactions. The semistructured Mini-International Neuropsychiatric Interview and psychometric questionnaires were administered before participants attended the ayahuasca ceremony and at 1 and 6 months after exposure. Subjective experiences were also recorded. RESULTS: Seven subjects from a sample of 40 reported having experienced intense challenging psychological effects during the ayahuasca ceremony. Four of those 7 subjects met the diagnostic criteria for 1 or more psychiatric disorder before the ayahuasca ceremony. One month after the ceremony, 2 of those subjects no longer showed psychiatric symptoms, whereas the symptoms of the other 2 were reduced considerably. Those results persisted at the 6-month follow-up. Inappropriate setting/context (poor guiding skills and screening) contributed to some of the challenging reactions. Most of the participants (6 of 7) did not take ayahuasca again during the study period. CONCLUSIONS: Based on the cases reported here, we suggest that although it is possible that participating in ayahuasca ceremonies may entail acute psychological negative reactions, those challenging experiences can also have positive long-term effects. Prospective research on the safety profile of ayahuasca and how it is affected by the context of different practices and safety strategies is therefore necessary.

Kinetic profile of N,N-dimethyltryptamine and ß-carbolines in saliva and serum after oral administration of ayahuasca in a religious context.

Ayahuasca is a beverage obtained from Banisteriopsis caapi plus Psychotria viridis. B. caapi contains the ß-carbolines harmine, harmaline, and tetrahydroharmine that are monoamine oxidase inhibitors and P. viridis contains N,N-dimethyltryptamine (DMT) that is responsible for the visionary effects of the beverage. Ayahuasca use is becoming a global phenomenon, and the recreational use of DMT and similar alkaloids has also increased in recent years; such uncontrolled use can lead to severe intoxications. In this investigation, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to study the kinetics of alkaloids over a 24 h period in saliva and serum of 14 volunteers who consumed ayahuasca twice a month in a religious context. We compared the area under the curve (AUC), maximum concentration (Cmax ), time to reach Cmax (Tmax ), mean residence time (MRT), and half-life (t1/2 ), as well as the serum/saliva ratios of these parameters. DMT and ß-carboline concentrations (Cmax ) and AUC were higher in saliva than in serum and the MRT was 1.5-3.0 times higher in serum. A generalized estimation equations (GEEs) model suggested that serum concentrations could be predicted by saliva concentrations, despite large individual variability in the saliva and serum alkaloid concentrations. The possibility of using saliva as a biological matrix to detect DMT, ß-carbolines, and their derivatives is very interesting because it allows fast noninvasive sample collection and could be useful for detecting similar alkaloids used recreationally that have considerable potential for intoxication.

Evaluation of the Cytotoxicity of Ayahuasca Beverages.

Ayahuasca is a beverage consumed at shamanic ceremonies and currently has gained popularity on recreational scenarios. It contains beta-carboline alkaloids and N,N-dimethyltryptamine, which possesses hallucinogenic effects. Only a few studies have elicited the psychoactive effects and the dose of such compounds on neurological dopaminergic cells or animals. In this work, we aimed to study the cytotoxic effects of these compounds present in ayahuasca beverages and on five different teas (Banisteriopsis caapi, Psychotria viridis, Peganum harmala, Mimosa tenuiflora and Dc Ab (commercial name)) preparations on dopaminergic immortalized cell lines. Moreover, a characterization of the derivative alkaloids was also performed. All the extracts were characterized by chromatographic systems and the effect of those compounds in cell viability and total protein levels were analyzed in N27 dopaminergic neurons cell line. This is the first article where cytotoxicity of ayahuasca tea is studied on neurological dopaminergic cells. Overall, results showed that both cell viability and protein contents decreased when cells were exposed to the individual compounds, as well as to the teas and to the two mixtures based on the traditional ayahuasca beverages.

Post-acute psychological effects of classical serotonergic psychedelics: a systematic review and meta-analysis.

BACKGROUND: Scientific interest in the therapeutic effects of classical psychedelics has increased in the past two decades. The psychological effects of these substances outside the period of acute intoxication have not been fully characterized. This study aimed to: (1) quantify the effects of psilocybin, ayahuasca, and lysergic acid diethylamide (LSD) on psychological outcomes in the post-acute period; (2) test moderators of these effects; and (3) evaluate adverse effects and risk of bias. METHODS: We conducted a systematic review and meta-analysis of experimental studies (single-group pre-post or randomized controlled trials) that involved administration of psilocybin, ayahuasca, or LSD to clinical or non-clinical samples and assessed psychological outcomes ⩾24 h post-administration. Effects were summarized by study design, timepoint, and outcome domain. RESULTS: A total of 34 studies (24 unique samples, n = 549, mean longest follow-up = 55.34 weeks) were included. Classical psychedelics showed significant within-group pre-post and between-group placebo-controlled effects on a range of outcomes including targeted symptoms within psychiatric samples, negative and positive affect-related measures, social outcomes, and existential/spiritual outcomes, with large between-group effect in these domains (Hedges' gs = 0.84 to 1.08). Moderator tests suggest some effects may be larger in clinical samples. Evidence of effects on big five personality traits and mindfulness was weak. There was no evidence of post-acute adverse effects. CONCLUSIONS: High risk of bias in several domains, heterogeneity across studies, and indications of publication bias for some models highlight the need for careful, large-scale, placebo-controlled randomized trials.

Antioxidant compounds from Banisteriopsis argyrophylla leaves as α-amylase, α-glucosidase, lipase, and glycation inhibitors.

Banisteriopsis argyrophylla belongs to the Malpighiaceae family, which is a species from Cerrado, also known as "cipó-prata" or "cipó-folha-de-prata." Several species of this family present biological potential. This work reports the chemical identification of the ethanol extract (EE) and its fractions from B. argyrophylla leaves and shows the analysis of the antioxidant activity and inhibitory effects on activities of α-amylase, α-glucosidase and lipase, and non-enzymatic glycation. The ethyl acetate fraction (EAF) and n-butanol fraction (BF) showed antioxidant activity, with IC50 values of 4.1 ± 0.1 and 4.8 ± 0.1 µg mL-1, respectively, by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, and IC50 values of 6046.3 ± 174.2 and 6264.2 ± 32.2 µmol Trolox eq g-1 by the oxygen radical absorbance capacity (ORAC) method. Furthermore, the DPPH method with these fractions presented electroactive species with antioxidant potential, as shown by the differential pulse voltammetry (DPV) method. The inhibitory effects of the EAF and BF were demonstrated by the following results: IC50 of 5.1 ± 0.3 and 2.5 ± 0.2 µg mL-1 for α-amylase, IC50 of 1093.5 ± 26.0 and 1250.8 ± 21.9 µg mL-1 for α-glucosidase, IC50 of 8.3 ± 4.1 and 4.4 ± 1.0 µg mL-1 for lipase, and IC50 of 1.3 ± 0.1 and 0.9 ± 0.1 µg mL-1 for glycation. Some bioactive compounds were identified by (-)-ESI-MS/MS, such as catechin, procyanidins, glycosylated flavonoids, kaempferol, and megastigmane glucosides. The antidiabetic activity of B.argyrophylla has been reported for the first time.

Modulatory effects of ayahuasca on personality structure in a traditional framework.

Ayahuasca is a psychoactive plant brew containing dimethyltryptamine (DMT) and monoamine oxidase inhibitors (MAOIs). It originates from the Amazon basin, where it is used primarily for ceremonial purposes. Ayahuasca tourists are now entering certain communities seeking alternative physical or psychological healing, as well as spiritual growth. RATIONALE: Recent evidence has shown that the similar acting psychedelic compound, psilocybin, facilitated long-term increases in trait openness following a single administration. OBJECTIVES: This paper assesses the impact of ayahuasca on personality in a traditional framework catering for ayahuasca tourists. METHOD: Within a mixed design, we examined the effect of ayahuasca on participants' personality (measured by the NEO Personality Inventory 3 questionnaire) across time (pre- to post-ayahuasca administration, and 6-month follow-up), relative to a comparison group (who did not ingest ayahuasca). RESULTS: The results demonstrated significant increases in agreeableness pre- and post-ayahuasca administration and significant reductions in neuroticism in 24 participants, relative to the comparison group. Both of these changes were sustained at 6-month follow-up, and trait level increases were also observed in openness at this stage. Additionally, greater perceived mystical experience (measured using the Mystical Experience Questionnaire 30) was associated with increased reductions in neuroticism. CONCLUSIONS: These findings, which indicate a positive mediating effect of ayahuasca on personality, support the growing literature suggesting potential therapeutic avenues for serotonergic psychedelics.

Changes in inflammatory biomarkers are related to the antidepressant effects of Ayahuasca.

BACKGROUND: Ayahuasca is a traditional Amazon brew and its potential antidepressant properties have recently been explored in scientific settings. We conducted a double-blind placebo-controlled trial of ayahuasca with treatment-resistant depression patients (n = 28) and healthy controls (n = 45). AIMS: We are evaluating the blood inflammatory biomarkers: C-reactive protein and interleukin 6, as a potential consequence of ayahuasca intake and their correlation with serum cortisol and brain-derived neurotrophic factor levels. Blood samples were collected at pre-treatment and 48 hours after substance ingestion to assess the concentration of inflammatory biomarkers, together with administration of the Montgomery-Åsberg Depression Rating Scale. RESULTS: At pre-treatment, patients showed higher C-reactive protein levels than healthy controls and a significant negative correlation between C-reactive protein and serum cortisol levels was revealed (rho = -0.40, n = 14). C-reactive protein in those patients was not correlated with Montgomery-Åsberg Depression Rating Scale scores. We observed a significant reduction of C-reactive protein levels across time in both patients and controls treated with ayahuasca, but not with placebo. Patients treated with ayahuasca showed a significant correlation (rho = + 0.57) between larger reductions of C-reactive protein and lower depressive symptoms at 48 hours after substance ingestion (Montgomery-Åsberg Depression Rating Scale). No significant result with respect to interleukin 6 and brain-derived neurotrophic factor was found. Furthermore, these biomarkers did not predict the antidepressant response or remission rates observed. CONCLUSIONS: These findings enhance the understanding of the biological mechanisms behind the observed antidepressant effects of ayahuasca and encourage further clinical trials in adults with depression.

Effects of ayahuasca on mental health and quality of life in naïve users: A longitudinal and cross-sectional study combination.

Ayahuasca is a hallucinogenic decoction used as a traditional medicine in several Amazonian regions. The ritualistic use of ayahuasca has spread throughout many countries, making it necessary to study its risks and benefits. Two sub-studies were designed for this investigation. In sub-study 1, a psychiatric interview and a battery of questionnaires were administered to subjects (n = 40) before their first ayahuasca use. Two follow-ups were conducted at 1 and 6 months. In sub-study 2, the same interview and battery of questionnaires were administered to long-term ayahuasca users (n = 23) and their scores were compared with those of the ayahuasca-naïve group. In the first assessment, nearly half (45%) of the naïve users were found to meet the diagnostic criteria for a psychiatric disorder. After the ayahuasca use, more than 80% of those subjects showed clinical improvements that persisted at 6 months. The questionnaires showed significant reductions in depression and psychopathology. Regarding sub-study 2, long-term users showed lower depression scores, and higher scores for self-transcendence and quality of life, as compared to their peers in sub-study 1. Further controlled and observational naturalistic studies assessing the eventual risks and potential benefits of ayahuasca are warranted.

Neuroprotective potential of Ayahuasca and untargeted metabolomics analyses: applicability to Parkinson's disease.

ETHNOPHARMACOLOGY RELEVANCE: Ayahuasca is a tea produced through decoction of Amazonian plants. It has been used for centuries by indigenous people of South America. The beverage is considered to be an ethnomedicine, and it is traditionally used for the treatment of a wide range of diseases, including neurological illness. Besides, some scientific evidence suggests it may be applicable to Parkinson's disease (PD) treatment. Thus, Ayahuasca deserves in depth studies to clarify its potential role in this disease. AIM OF THE STUDY: This study aimed to use an untargeted metabolomics approach to evaluate the neuroprotective potential of the Ayahuasca beverage, the extracts from its matrix plants (Banisteriopsis caapi and Psychotria viridis), its fractions and its main alkaloids on the viability of SH-SY5Y neuroblastoma cells in an in vitro PD model. MATERIAL AND METHODS: The cytotoxicity of Ayahuasca, crude extracts, and fractions of B. caapi and P. viridis, as well as neuroprotection promoted by these samples in a 6-hydroxydopamine (6-OHDA)-induced neurodegeneration model, were evaluated by the MTT assay at two time-points: 48 h (T1) and 72 h (T2). The main alkaloids from Ayahuasca matrix plants, harmine (HRE) and N,N-dimethyltryptamine (DMT), were also isolated and evaluated. An untargeted metabolomics approach was developed to explore the chemical composition of samples with neuroprotective activity. Ultra-Performance Liquid Chromatography coupled to Electrospray Ionisation and Time-of-Flight (UPLC-ESI-TOF) metabolome data was treated and further analysed using multivariate statistical analyses (MSA): principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). The metabolites were dereplicated using the Dictionary of Natural Products and an in house database. The main alkaloids were also quantified by UPLC-MS/MS. RESULTS: The samples did not cause cytotoxicity in vitro and three of samples intensely increased cell viability at T1. The crude extracts, alkaloid fractions and HRE demonstrated remarkable neuroprotective effect at T2 while the hydroalcoholic fractions demonstrated this neuroprotective effect at T1 and T2. Several compounds from different classes, such as ß-carbolines and monoterpene indole alkaloids (MIAs) were revealed correlated with this property by MSA. Additionally, a total of 2419 compounds were detected in both ionisation modes. HRE showed potent neuroprotective action at 72 h, but it was not among the metabolites positively correlated with the most efficacious neuroprotective profile at either time (T1 and T2). Furthermore, DMT was statistically important to differentiate the dataset (VIP value > 1), although it did not exhibit sufficient neuroprotective activity by in vitro assay, neither a positive correlation with T1 and T2 neuroprotective profile, which corroborated the MSA results. CONCLUSION: The lower doses of the active samples stimulated neuronal cell proliferation and/or displayed the most efficacious neuroprotection profile, namely by preventing neuronal damage and improving cell viability against 6-OHDA-induced toxicity. Intriguingly, the hydroalcoholic fractions exhibited enhanced neuroprotective effects when compared to other samples and isolated alkaloids. This finding corroborates the significance of a holistic approach. The results demonstrate that Ayahuasca and its base plants have potential applicability for PD treatment and to prevent its progression differently from current drugs to treat PD.

Pesquisas com ayahuasca na psicologia: revisão de literatura sobre o potencial terapêutico / Research with ayahuasca in psychology: a literature review of its therapeutic potential

A Ayahuasca é uma bebida alucinógena utilizada em contexto religioso, sendo associada a melhorias na saúde mental dos usuários. O presente estudo teve como objetivo fazer um levantamento da produção de pesquisas que avaliam o seu potencial terapêutico no campo da Psicologia. Foi realizada uma revisão narrativa de literatura com os descritores "Psicologia" e "Ayahuasca" indexados no portal CAPES, nas plataformas Medline e Scielo. Foram obtidos 34 artigos e foram aplicados critérios de inclusão ­ serem escritos nas línguas portuguesa ou inglesa, e possuírem o descritor "Ayahuasca" no título ­ e de exclusão ­ não abordarem o uso terapêutico da ayahuasca como problema de pesquisa. Após a filtragem, obteve-se 8 artigos publicados entre 2006 e 2018, divididos em 10 estudos, sendo 7 de pesquisa básica e 3 de pesquisa aplicada. Conclui-se que a produção de estudos sobre a eficácia terapêutica da Ayahuasca e seus efeitos na saúde mental dos usuários é recente e escassa. É importante que estudos futuros abordem além de parâmetros psicopatológicos ou farmacológicos questões sociais e culturais atrelados ao uso de substâncias. É essencial que particularidades do ambiente no qual a substância foi ingerida e da história de vida do usuário sejam consideradas e investigadas minunciosamente

The Ayahuasca is a hallucinogenic drink used in religious context and its use is associated with improvements in mental health of users. This study aimed to do a survey of the researches that evaluate the therapeutic potential of Ayahuasca in Psychology. A narrative literature review was performed with the descriptors "Psychology" and "Ayahuasca" indexed on the CAPES portal, on Medline and Scielo platforms. Thirty-four articles were obtained and inclusion criteria were applied - written in Portuguese or English, and having the descriptor "Ayahuasca" in the title - and exclusion - not addressing the therapeutic use of ayahuasca as a research problem. After filtering, we obtained 8 articles published between 2006 and 2018, divided into 10 studies: 7 of basic research and 3 of applied research. It is concluded that the production of studies on the therapeutic efficacy of Ayahuasca and its effects on users' mental health is recent and scarce. It is important that future studies address beyond psychopathological or pharmacological parameters, analising social and cultural issues linked to substance use. It is essential that particularities of the environment in which the substance was taken and of the user's life history are considered and investigated in detail.