Human brain effects of DMT assessed via EEG-fMRI.

Psychedelics have attracted medical interest, but their effects on human brain function are incompletely understood. In a comprehensive, within-subjects, placebo-controlled design, we acquired multimodal neuroimaging [i.e., EEG-fMRI (electroencephalography-functional MRI)] data to assess the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT) on brain function in 20 healthy volunteers. Simultaneous EEG-fMRI was acquired prior to, during, and after a bolus IV administration of 20 mg DMT, and, separately, placebo. At dosages consistent with the present study, DMT, a serotonin 2A receptor (5-HT2AR) agonist, induces a deeply immersive and radically altered state of consciousness. DMT is thus a useful research tool for probing the neural correlates of conscious experience. Here, fMRI results revealed robust increases in global functional connectivity (GFC), network disintegration and desegregation, and a compression of the principal cortical gradient under DMT. GFC × subjective intensity maps correlated with independent positron emission tomography (PET)-derived 5-HT2AR maps, and both overlapped with meta-analytical data implying human-specific psychological functions. Changes in major EEG-measured neurophysiological properties correlated with specific changes in various fMRI metrics, enriching our understanding of the neural basis of DMT's effects. The present findings advance on previous work by confirming a predominant action of DMT-and likely other 5-HT2AR agonist psychedelics-on the brain's transmodal association pole, i.e., the neurodevelopmentally and evolutionarily recent cortex that is associated with species-specific psychological advancements, and high expression of 5-HT2A receptors.

Shared functional connectome fingerprints following ritualistic ayahuasca intake.

The knowledge that brain functional connectomes are unique and reliable has enabled behaviourally relevant inferences at a subject level. However, whether such "fingerprints" persist under altered states of consciousness is unknown. Ayahuasca is a potent serotonergic psychedelic which produces a widespread dysregulation of functional connectivity. Used communally in religious ceremonies, its shared use may highlight relevant novel interactions between mental state and functional connectome (FC) idiosyncrasy. Using 7T fMRI, we assessed resting-state static and dynamic FCs for 21 Santo Daime members after collective ayahuasca intake in an acute, within-subject study. Here, connectome fingerprinting revealed FCs showed reduced idiosyncrasy, accompanied by a spatiotemporal reallocation of keypoint edges. Importantly, we show that interindividual differences in higher-order FC motifs are relevant to experiential phenotypes, given that they can predict perceptual drug effects. Collectively, our findings offer an example of how individualised connectivity markers can be used to trace a subject's FC across altered states of consciousness.

Long-term ayahuasca use is associated with preserved global cognitive function and improved memory: a cross-sectional study with ritual users.

Although several studies have been conducted to elucidate the relationship between psychedelic consumption and cognition, few have focused on understanding the long-term use influence of these substances on these variables, especially in ritualistic contexts.  To verify the influence of ritualistic ayahuasca consumption on the cognition of experienced ayahuasca religious users (> 20 years) and beginners (< 3 years), which participated in rituals of the Centro Luz Divina (CLD), a Santo Daime church in Brazil. Observational, descriptive, and cross-sectional study was carried out in which 48 people participated divided into three groups: (a) experienced ayahuasca users (n = 16), (b) beginner ayahuasca users (n = 16) and (c) control group (n = 16). All groups were matched by sex, age, and education and contained 8 women and 8 men. Cognition was assessed with the WASI (intelligence quotient), Digit Span (verbal working memory), Corsi Block-Tapping Task (visuospatial-related and working memory), Rey-Osterrieth Complex Figure test (visual perception, immediate memory), and Wisconsin Card Sorting and Five Digit Test (executive functions). Groups were homogenous in terms of sociodemographic characteristics, with participants presenting average intellectual performance. There was no evidence of cognitive decline amongst ayahuasca users. The experienced group showed higher scores compared to the less experienced group in the Digit Span and Corsi Block-Tapping tasks, which assess working verbal and visuospatial memories respectively. We confirmed the botanical identities of Psychotria viridis and Banisteriopsis caapi and the presence of the alkaloids both in the plants and in the brew. Short and long-term ayahuasca consumption does not seem to alter human cognition, while long-term use seems to be associated with improvements in aspects of working memory when compared with short-term use.

Ayahuasca and Dimethyltryptamine Adverse Events and Toxicity Analysis: A Systematic Thematic Review.

The objective of this paper is to conduct a systematic thematic review of adverse events, safety, and toxicity of traditional ayahuasca plant preparations and its main psychoactive alkaloids (dimethyltryptamine [DMT], harmine, harmaline, and tetrahydroharmine), including discussing clinical considerations (within clinical trials or approved settings). A systematic literature search of preclinical, clinical, epidemiological, and pharmacovigilance data (as well as pertinent reviews and case studies) was conducted for articles using the electronic databases of PubMed and Web of Science (to 6 July 2023) and PsycINFO, ClinicalTrials.gov, and Embase (to 21 September 2022) and included articles in English in peer-reviewed journals. Additionally, reference lists were searched. Due to the breadth of the area covered, we presented the relevant data in a thematic format. Our searches revealed 78 relevant articles. Data showed that ayahuasca or DMT is generally safe; however, some adverse human events have been reported. Animal models using higher doses of ayahuasca have shown abortifacient and teratogenic effects. Isolated harmala alkaloid studies have also revealed evidence of potential toxicity at higher doses, which may increase with co-administration with certain medications. Harmaline revealed the most issues in preclinical models. Nevertheless, animal models involving higher-dose synthetic isolates may not necessarily be able to be extrapolated to human use of therapeutic doses of plant-based extracts. Serious adverse effects are rarely reported within healthy populations, indicating an acceptable safety profile for the traditional use of ayahuasca and DMT in controlled settings. Further randomized, controlled trials with judicious blinding, larger samples, and longer duration are needed.

Comparative study of sample preparation procedures to determine the main compounds in ayahuasca beverages by QuEChERS and high-performance liquid chromatography analysis.

INTRODUCTION: Ayahuasca is a psychoactive drink originally consumed by indigenous people of the Amazon. The lack of regulation of this drink leads to uncontrolled consumption, and it is often consumed in religious contexts. OBJECTIVE: The aim of this work is to compare three miniaturised extraction techniques for extracting the main ayahuasca compounds from beverages. METHODOLOGY: Three sample pretreatment techniques were evaluated (dispersive liquid-liquid microextraction [DLLME], microextraction by packed sorbent [MEPS] and QuEChERS [Quick, Easy, Cheap, Effective, Rugged and Safe]) for the simultaneous extraction of N,N-dimethyltryptamine (DMT), tetrahydroharmine (THH), harmine, harmaline, harmol and harmalol from ayahuasca beverage samples. Then, the most promising technique (QuEChERS) was chosen to pre-concentrate the analytes, subsequently detected by high-performance liquid chromatography coupled to a diode array detector (HPLC-DAD). RESULTS: The procedure was optimised, with the final conditions being 500 µL of extractor solvent, 85 mg of primary secondary amine (PSA) and 4 s of vortexing. The analytical method was validated, showing to be linear between 0.16 and 10 µg/mL for ß-carbolines and between 0.016 and 1 µg/mL for DMT, with coefficients of determination (R2) between 0.9968 and 0.9993. The limit of detection (LOD) and lower limit of quantification (LLOQ) were 0.16 µg/mL for all compounds, except for DMT (0.016 µg/mL) and extraction efficiencies varied between 60.2% and 88.0%. CONCLUSION: The analytical methodology proved to be accurate and precise, with good linearity, LODs and LLOQs. This method has been fully validated and successfully applied to ayahuasca beverage samples.

Default Mode Network Modulation by Psychedelics: A Systematic Review.

Psychedelics are a unique class of drug that commonly produce vivid hallucinations as well as profound psychological and mystical experiences. A grouping of interconnected brain regions characterized by increased temporal coherence at rest have been termed the Default Mode Network (DMN). The DMN has been the focus of numerous studies assessing its role in self-referencing, mind wandering, and autobiographical memories. Altered connectivity in the DMN has been associated with a range of neuropsychiatric conditions such as depression, anxiety, post-traumatic stress disorder, attention deficit hyperactive disorder, schizophrenia, and obsessive-compulsive disorder. To date, several studies have investigated how psychedelics modulate this network, but no comprehensive review, to our knowledge, has critically evaluated how major classical psychedelic agents-lysergic acid diethylamide, psilocybin, and ayahuasca-modulate the DMN. Here we present a systematic review of the knowledge base. Across psychedelics there is consistent acute disruption in resting state connectivity within the DMN and increased functional connectivity between canonical resting-state networks. Various models have been proposed to explain the cognitive mechanisms of psychedelics, and in one model DMN modulation is a central axiom. Although the DMN is consistently implicated in psychedelic studies, it is unclear how central the DMN is to the therapeutic potential of classical psychedelic agents. This article aims to provide the field with a comprehensive overview that can propel future research in such a way as to elucidate the neurocognitive mechanisms of psychedelics.

Understanding ayahuasca effects in major depressive disorder treatment through in vitro metabolomics and bioinformatics.

Emerging insights from metabolomic-based studies of major depression disorder (MDD) are mainly related to biochemical processes such as energy or oxidative stress, in addition to neurotransmission linked to specific metabolite intermediates. Hub metabolites represent nodes in the biochemical network playing a critical role in integrating the information flow in cells between metabolism and signaling pathways. Limited technical-scientific studies have been conducted to understand the effects of ayahuasca (Aya) administration in the metabolism considering MDD molecular context. Therefore, this work aims to investigate an in vitro primary astrocyte model by untargeted metabolomics of two cellular subfractions: secretome and intracellular content after pre-defined Aya treatments, based on DMT concentration. Mass spectrometry (MS)-based metabolomics data revealed significant hub metabolites, which were used to predict biochemical pathway alterations. Branched-chain amino acid (BCAA) metabolism, and vitamin B6 and B3 metabolism were associated to Aya treatment, as "housekeeping" pathways. Dopamine synthesis was overrepresented in the network results when considering the lowest tested DMT concentration (1 µmol L-1). Building reaction networks containing significant and differential metabolites, such as nicotinamide, L-DOPA, and L-leucine, is a useful approach to guide on dose decision and pathway selection in further analytical and molecular studies.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Report: Serotonergic Psychedelic Treatments for Major Depressive Disorder.

OBJECTIVE: Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence and provide a consensus recommendation for the clinical use of psychedelic treatments for major depressive disorder. METHODS: A systematic review was conducted to identify contemporary clinical trials of serotonergic psychedelics for the treatment of major depressive disorder and cancer-related depression. Studies published between January 1990 and July 2021 were identified using combinations of search terms, inspection of bibliographies and review of other psychedelic reviews and consensus statements. The levels of evidence for efficacy were graded according to the Canadian Network for Mood and Anxiety Treatments criteria. RESULTS: Only psilocybin and ayahuasca have contemporary clinical trials evaluating antidepressant effects. Two pilot studies showed preliminary positive effects of single-dose ayahuasca for treatment-resistant depression (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy and safety to an active comparator (escitalopram with supportive psychotherapy) in major depressive disorder, with additional randomized controlled trials showing efficacy specifically in cancer-related depression (Level 3 evidence). There was only one open-label trial of psilocybin in treatment-resistant unipolar depression (Level 4 evidence). Small sample sizes and functional unblinding were major limitations in all studies. Adverse events associated with psychedelics, including psychological (e.g., psychotomimetic effects) and physical (e.g., nausea, emesis and headaches) effects, were generally transient. CONCLUSIONS: There is currently only low-level evidence to support the efficacy and safety of psychedelics for major depressive disorder. In Canada, as of 2022, psilocybin remains an experimental option that is only available through clinical trials or the special access program. As such, Canadian Network for Mood and Anxiety Treatments considers psilocybin an experimental treatment and recommends its use primarily within clinical trials, or, less commonly, through the special access program in rare, special circumstances.

Ancient medicine for a modern disease: traditional Amazonian medicine to treat substance use disorders.

Background: There exists an underexploited opportunity to develop innovative therapeutic approaches to SUDs based upon the complementarity between modern and traditional health systems.Objectives: Illustrate the feasibility and potentiality of such an approach through the comprehensive description of Takiwasi Center's treatment model and program, where health concepts and practices from traditional Amazonian medicine work synergistically with modern psychotherapy and medicine in an intercultural dialog to assist in the rehabilitation of people suffering from SUDs.Methods: The description was built from a review of the literature, institutional data, participatory observation and unstructured interviews with staff, researchers and patients during treatment.Results: Since the foundation of the Takiwasi Center in 1992 in the peruvian Amazon, more than a thousand patients with different socio-cultural, ethnic and religious backgrounds have received residential treatment. We present how traditional Amazonian medicine techniques and health concepts cooperate to complement modern psychology in a therapeutic community setting and propose some hypotheses about the neurobiological, psycho-emotional and spiritual healing mechanisms triggered by the program to help people identify and heal the roots of their substance misuse and addictive behavior. We also summarize quantitative outcomes during treatment showing significant improvements in a wide variety of mental health indicators.Conclusion: Takiwasi Center's program is an option for people seeking non-conventional treatment who are sensitive to traditional Amazonian medicine practices and ready to explore the roots of their addiction. From this intercultural approach, some lessons could emerge toward a broader understanding of SUDs that may result in better patient care.

'Everybody's creating it along the way': ethical tensions among globalized ayahuasca shamanisms and therapeutic integration practices.

Ayahuasca has a variety of traditional uses, yet there is a growing global interest in its potential therapeutic benefits for mental health conditions. Novel approaches to psychotherapy are emerging to address the needs of ayahuasca users to prepare as well as to guide them in 'integrating' their powerful psychedelic experiences, yet there is little discussion on the ethical frameworks that may structure these therapeutic processes or the social and cultural assumptions that influence the assignment of ayahuasca as a medicine. Based on ethnographic fieldwork in San Martín and Loreto, Peru, I examine the varied social meanings and uses of ayahuasca in the Peruvian vegetalista tradition and the potential ethical tensions among curanderos, mental health practitioners, and ayahuasca retreat centers. Practitioners and ayahuasca centers are left with navigating globalized concepts of mental health and ethics while attempting to remain authentic to local ontologies of healing, care, and safety.

Psychedelic-inspired approaches for treating neurodegenerative disorders.

Psychedelics are increasingly being recognized for their potential to treat a wide range of brain disorders including depression, post-traumatic stress disorder (PTSD), and substance use disorder. Their broad therapeutic potential might result from an ability to rescue cortical atrophy common to many neuropsychiatric and neurodegenerative diseases by impacting neurotrophic factor gene expression, activating neuronal growth and survival mechanisms, and modulating the immune system. While the therapeutic potential of psychedelics has not yet been extended to neurodegenerative disorders, we provide evidence suggesting that approaches based on psychedelic science might prove useful for treating these diseases. The primary target of psychedelics, the 5-HT2A receptor, plays key roles in cortical neuron health and is dysregulated in Alzheimer's disease. Moreover, evidence suggests that psychedelics and related compounds could prove useful for treating the behavioral and psychological symptoms of dementia (BPSD). While more research is needed to probe the effects of psychedelics in models of neurodegenerative diseases, the robust effects of these compounds on structural and functional neuroplasticity and inflammation clearly warrant further investigation.

Effects of ayahuasca and its alkaloids on substance use disorders: an updated (2016-2020) systematic review of preclinical and human studies.

Ayahuasca is a hallucinogenic/psychedelic traditionally used for ritual and therapeutic purposes. One such therapeutic use is related to Substance Use Disorders (SUDs). A previous systematic review of preclinical and human studies published until 2016 suggested that ayahuasca and its alkaloids have therapeutic effects in the treatment of SUDs. To conduct an update of this previous review. A systematic review of quantitative studies which analyzed the effects of ayahuasca and its alkaloids on drug use (primary outcome) and other measures (secondary outcomes) related to SUDs was conducted, including articles from 2016 to 2020. Nine studies (four preclinical, five observational) were included in the review. Preclinical studies in rodents reported reductions in amphetamine self-administration and anxiety, and in alcohol- and methylphenidate-induced conditioned place preference. Observational studies among healthy ritual ayahuasca users and patients with SUDs reported reductions in drug use, anxiety, and depression, and increases in quality of life and well-being. We replicated the findings of the previous review suggesting that ayahuasca and its alkaloids have therapeutic effects in the treatment of SUDs. However, translation of preclinical data to humans is limited, observational studies do not allow us to infer causality, and there is a lack of standardization on ayahuasca doses. Although promising, randomized, controlled trials are needed to better elucidate these results. The PROSPERO ID for this study is CRD42020192046.

Effects of ayahuasca on the endocannabinoid system of healthy volunteers and in volunteers with social anxiety disorder: Results from two pilot, proof-of-concept, randomized, placebo-controlled trials.

OBJECTIVE: To assess 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. METHODS: Post hoc analysis of endocannabinoid plasma levels (baseline, 90 and 240 min after drug intake) from two parallel-group, randomized, placebo-controlled trials. In Study 1, 20 healthy volunteers ingested ayahuasca (average 1.58 mg/ml dimethyltryptamine (DMT)) or placebo, and in Study 2, 17 volunteers with SAD received ayahuasca (average 0.680 mg/ml DMT) or placebo. RESULTS: A significant difference was observed in AEA concentrations in Study 2 after ayahuasca intake (Χ2 (2) = 6.5, p = 0.03, Friedman test), and near significant differences (increases) were observed between baseline and 90 (Z = 0, p = 0.06, Wilcoxon test) and 240 (Z = 10, p = 0.06) minutes after ayahuasca intake. CONCLUSIONS: Although our findings suggest that ayahuasca could modulate AEA levels in SAD patients, the high interindividual variability in both trials and the small samples preclude definitive conclusions. More research with larger samples is needed to better understand the effects of ayahuasca and other hallucinogens in the endocannabinoid system.

N,N-dimethyltryptamine and Amazonian ayahuasca plant medicine.

OBJECTIVE: Reports have indicated possible uses of ayahuasca for the treatment of conditions including depression, addictions, post-traumatic stress disorder, anxiety and specific psychoneuroendocrine immune system pathologies. The article assesses potential ayahuasca and N,N-dimethyltryptamine (DMT) integration with contemporary healthcare. The review also seeks to provide a summary of selected literature regarding the mechanisms of action of DMT and ayahuasca; and assess to what extent the state of research can explain reports of unusual phenomenology. DESIGN: A narrative review. RESULTS: Compounds in ayahuasca have been found to bind to serotonergic receptors, glutaminergic receptors, sigma-1 receptors, trace amine-associated receptors, and modulate BDNF expression and the dopaminergic system. Subjective effects are associated with increased delta and theta oscillations in amygdala and hippocampal regions, decreased alpha wave activity in the default mode network, and stimulations of vision-related brain regions particularly in the visual association cortex. Both biological processes and field of consciousness models have been proposed to explain subjective effects of DMT and ayahuasca, however, the evidence supporting the proposed models is not sufficient to make confident conclusions. Ayahuasca plant medicine and DMT represent potentially novel treatment modalities. CONCLUSIONS: Further research is required to clarify the mechanisms of action and develop treatments which can be made available to the general public. Integration between healthcare research institutions and reputable practitioners in the Amazon is recommended.

Ayahuasca may help to improve self-compassion and self-criticism capacities.

OBJECTIVE: Ayahuasca is a psychedelic brew that originated in the Amazon basin. The psychological effects of this drug are becoming better understood due to the growing research interest in identifying new potential therapeutic agents for the treatment of emotion dysregulation and other disorders. Previous studies suggest that ayahuasca enhances mindfulness-related capacities (decentering, non-judging, non-reacting and acceptance) and emotion regulation. The aim of the present exploratory study was to determine the effects of ayahuasca on self-compassion in a community sample. METHODS: We administered validated questionnaires (the Self-Compassion Scale-Short Form and Forms of Self-Criticism and Self-Reassurance) to evaluate pre-post changes in self-compassion and self-criticism/self-reassurance in 45 volunteers (27 women; 60%) before and after (≤24 h) an ayahuasca ceremony. Most participants (n = 29; 67.4%) had previously used ayahuasca. RESULTS: Ayahuasca resulted in significant improvements, with medium to large effect sizes (η2  = 0.184-0.276), in measures of self-compassion (p < 0.05), self-criticism (p < 0.01) and self-reassurance (p < 0.01). CONCLUSIONS: The findings of this study suggest that ayahuasca promotes well-being and self-compassion, which could have a therapeutic effect on individuals with negative affect and other psychopathological conditions. Large, controlled studies are needed to confirm these findings.

Classic psychedelics and alcohol use disorders: A systematic review of human and animal studies.

Classic psychedelics refer to substances such as lysergic acid diethylamide (LSD), psilocybin, ayahuasca, and mescaline, which induce altered states of consciousness by acting mainly on 5-HT2A receptors. Recently, the interest of psychedelics as pharmacological treatment for psychiatric disorders has increased significantly, including their use on problematic use of alcohol. This systematic review is aimed to analyse the last two decades of studies examining the relationship between classic psychedelics and alcohol consumption. We searched PubMed and PsycInfo for human and preclinical studies published between January 2000 to December 2021. The search identified 639 publications. After selection, 27 studies were included. Human studies (n = 20) generally show promising data and seem to indicate that classic psychedelics could help reduce alcohol consumption. Nevertheless, some of these studies present methodological concerns such as low number of participants, lack of control group or difficulty in determining the effect of classic psychedelics in isolation. On the other hand, preclinical studies (n = 7) investigating the effect of these compounds on voluntary alcohol consumption are scarce and show some conflicting data. Among these compounds, psilocybin seems to show the most consistent data indicating that this compound could be a potential candidate to treat alcohol use disorders. In the absence of understanding the biological and/or psychological mechanisms, more studies including methodological quality parameters are needed to finally determine the effects of classic psychedelics on alcohol consumption.

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.

Psychosocial and Drug Use Assessment of Regular vs. Non-Regular Ayahuasca Users in a Brazilian Sample: a Web-Based Survey.

Background: Preliminary evidence suggests that long-term ayahuasca use is associated with better psychosocial outcomes and less drug use; however, available data on the association between ayahuasca intake frequency and psychosocial outcomes is limited. Objectives: We sought to characterize and investigate the association of regular ayahuasca use, as compared to non-regular use, on licit (alcohol and tobacco) and illicit (cannabis, psychostimulants, psychedelics, and non-medical opioids) drug use and psychosocial outcomes. Methods: An online-based cross-sectional survey was taken among people who use ayahuasca in Brazil assessing sociodemographic, drug and ayahuasca use, anxiety and depression (HAD-S), intrinsic religiosity (IRI), negative and positive affects (PANAS), satisfaction with life (SWLS), and five quality of life domains (WHOQOL-Brief). Multivariate regressions for each psychosocial outcome and drug use were performed comparing regular to non-regular ayahuasca users while correcting for sociodemographic variables. Results: A total of 286 valid answers were retrieved, divided into people with regular (n = 101) and non-regular (n = 185) ayahuasca use. Groups had similar sociodemographic profiles and lifetime use of drugs. In the multivariate analysis, regular use of ayahuasca was associated with lower anxiety (B: -0.97), negative affect (B: -2.62), general (B: 0.22) and physical (B: 0.17) quality of life, higher intrinsic religiosity scores (B: 4.16), and less past-month licit (OR = 0.30) and illicit (OR = 0.49) use of substances. Conclusions: Our results show that ceremonial regular ayahuasca compared to non-regular use is associated with better psychosocial and mental health outcomes and less drug use. Studies with repeated ayahuasca administration and extended follow-ups are essential to clarify the nature of ayahuasca's therapeutic effects and to guide future clinical research.

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.