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This paper focuses on a single case of ayahuasca-assisted grief therapy for the prevention of complicated grief, conducted within a clinical trial. The participant, a woman in her thirties who lost her father to cancer, completed a 9-session process of Meaning Reconstruction Therapy (MRT) organised around two ayahuasca sessions. Following each psychedelic experience, she also completed a psychedelic integration session. The case study investigates the effect of the intervention, the observed changes in the participant, and the potential processes of change which may account for this improvement. The analysis relies on a qualitative narrative approach to examine the content of each therapy session, as well as on the psychometric measures completed at baseline, post-treatment, and at the three-month follow-up. These results are linked to emerging theories in the field, with a particular focus on the role of meaning reconstruction, psychological flexibility, and a continuing bond with the deceased. [ABSTRACT FROM AUTHOR]

Background: There is ongoing research into the potential use of psychedelics and 3,4-methylenedioxy-methamphetamine (MDMA) as alternatives to commonly used medications for treating major depressive and anxiety disorders. Aims: We aimed to assess the efficacy of psychedelics and MDMA in managing depressive and anxiety symptoms and evaluate their safety profiles. Methods: We searched five databases for randomized controlled trials of psychedelics and MDMA targeting depressive and anxiety symptoms and conducted a meta-analysis using a random effects model when possible. The review protocol is registered in PROSPERO under CRD42022341325. Results: Psilocybin induced a rapid and sustained reduction in depressive and anxiety symptoms in patients with major depressive disorder and in patients with life-threatening cancer. MDMA induced a decrease in depressive symptoms in patients with life-threatening cancer, autism spectrum disorder, and post-traumatic stress disorder. MDMA's effect size was either negligible or negative in reducing generalized anxiety symptoms, but MDMA reduced social anxiety symptoms. Ayahuasca induced a reduction in depressive symptoms in individuals with treatment-resistant major depressive and personality disorders. Lysergic acid diethylamide (LSD) induced a decrease in anxiety symptoms in individuals with life-threatening cancer. Psilocybin's adverse effects were noticeable for elevated blood pressure, headaches, and panic attacks. For MDMA, elevated blood pressure, headaches, panic attacks, and feeling cold were noticeable. Conclusions: Psychedelics (psilocybin, ayahuasca, and LSD) and MDMA have the potential to induce a reduction in depressive and anxiety symptoms. Adverse effects are noticed. Rigorous randomized controlled studies with larger sample sizes utilizing instruments with better reliability and validity are warranted. [ABSTRACT FROM AUTHOR]

Recent years have witnessed an unprecedented increase in the search for the use of psychedelics in improving physical and mental health. Anaesthesia has evolved since very early times, born from the need to eliminate pain and reduce suffering and there are reports of the use of anaesthetics to achieve mystical states since the nineteenth century. Nowadays, the renaissance of psychedelics in anaesthesia has been inspired by their potential in the treatment of chronic pain syndromes, palliative care and in the emergency department and pre‐hospital care with the administration of psychedelics in cases of ischaemia, given their potential in neuroprotection. Although there are already some published protocols for the administration of psychedelics in patients with mental illness, little has been addressed concerning non‐mental medical applications. In this sense, in patients with multiple comorbidities, functional limitations and polymedicated, the anaesthetist may play a fundamental role, not only in clinical practice, but also in translational research. This article focuses on the description of psychedelics, with a particular focus on dimethyltryptamine (DMT) and ayahuasca pharmacology, effects, safety and toxicity. A detailed description of the role of the anaesthetist in clinical and experimental research is provided, from participant's screening to preparation and dosing session, expected adverse effects and how to manage them, based on the protocol and standard procedures of a current study with neuroimaging during the psychedelic experience. Specific considerations regarding the management of psychedelic toxicity are also provided as well as future directions for safe psychedelic use in clinical practice. [ABSTRACT FROM AUTHOR]

Although the tobacco plant has been employed as a medicinal and sacred herb by Indigenous cultures across the Americas, its usage drastically changed after the 15th-century colonial arrival; its large-scale commodification and global marketing once brought to Europe lead to hedonic and addictive uses harmful to health. As a consequence, tobacco smoking is now one of the largest public health problems worldwide. However, in the Peruvian Amazon, a region of origin of tobacco species, Indigenous healers still know how to use the plant for therapeutic purposes. Due to a general disregard of Indigenous knowledge and stigma, these uses have however not so far been clinically investigated. We hence conducted for the first time a clinical field study assessing a sample of patients treated by a traditional healer specialized in tobacco in the Peruvian Amazon (observational design, pilot study, N = 27). The study was conducted within a transdisciplinary and multi-epistemic medical frame, in close partnership with an Amazonian healer. We used validated self-report scales to quantitatively assess mental health variables before and after the weeklong treatment, and mixed-methods to report experienced effects. Paired-samples t-tests comparing pre- and post-treatment scores revealed significant reductions in anxiety, depression, perceived stress, and general symptom indicators. Experienced effects included initial physical discomfort, followed by psychologically or existentially/spiritually significant insights. Our findings point to a sophisticated therapeutic approach based on Indigenous knowledge of tobacco applications, which should be further investigated. The study also contributes to the burgeoning scientific field on therapeutic uses of contentious psychoactive plants. [ABSTRACT FROM AUTHOR]

Emerging evidence indicates that ayahuasca consumption may have beneficial mental health effects. This study undertakes the largest analysis to date of associations between naturalistic ayahuasca use and current mental health status via an online cross-sectional survey. The sample included 7,576 participants (average age 41, 47% female) who had consumed ayahuasca in religious, traditional, or non-traditional settings in over 50 countries. Bivariate analysis, multivariate linear regressions and generalized structural equation modeling were used to explore associations between ayahuasca use variables, current mental health (K10, SF-12 MCS), and psychological well-being change (PWG). The number of ayahuasca uses was found to be positively associated with current mental health status (all measures), and this remained highly significant in multivariate models, with little evidence of associations diminishing over time. Variables such as the strength of the mystical experience, self-insights, and community/social variables were also positively associated with current mental health and PWG, while acute extreme fear and integration difficulties were negatively associated. Findings suggest that naturalistic ayahuasca use is associated with better current mental health status and enhanced psychological wellbeing for individuals with and without a history of mental illness, independent of community effects, with certain variables contributing positively or negatively to these effects. [ABSTRACT FROM AUTHOR]

The article discusses the unique features and therapeutic potential of N,N-dimethyltryptamine (DMT) beyond classical psychedelics. It highlights DMT's distinct effects, receptor interactions, lack of tolerance, and potential therapeutic applications in mental health treatment. The text also explores DMT's endogenous production in the human body, its unique phenomenology, pharmacokinetic properties, mechanisms of action, and effects on neuroplasticity. While research on DMT is still in its early stages, the compound shows promise as a valuable candidate for psychedelic therapeutics, offering different treatment outcomes compared to other psychedelics. [Extracted from the article]

Psychedelics have recently (re)emerged as therapeutics of high potential for multiple mental health conditions, including substance use disorders (SUDs). Despite early mid-20th century anecdotal reports and pilot studies demonstrating the possibility of these substances in efficaciously treating conditions such as alcohol and opioid use disorders, legal restrictions and social stigma have historically hindered further research into this area. Nevertheless, concurrent with the rise in SUDs and other mental health conditions, researchers have again turned their attention to these compounds, searching for differing pharmacological targets as well as more holistic treatments that might increase patient adherence and efficacy. The aim of this review is to examine the emerging evidence-based data with regards to the therapeutic treatment of SUDs with the psychedelic compounds psilocybin, ketamine, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), ayahuasca, ibogaine and peyote. [ABSTRACT FROM AUTHOR]

BACKGROUND: Refugees and immigrants can experience complex stressors from the process of immigration that can have lasting and severe long-term mental health consequences. Experiences after ayahuasca ingestion are shown to produce positive effects on psychological wellbeing and mental health, including anecdotal reports of improved symptoms of trauma and related disorders. However, data on the longitudinal health impact of naturalistic ayahuasca use in Middle Eastern and North African (MENA) immigrant and refugee populations is limited. AIMS: The current longitudinal online survey study was conducted to gather prospective data on ceremonial ayahuasca use in a group (N = 15) of primarily female MENA immigrants and refugees and to provide further insight into the patterns and outcomes surrounding that use. The study sought to assess self-reported changes in physical and mental health, well-being, and psychological functioning, examine relationships between aspects of individual mindset (e.g., psychedelic preparedness) prior to ayahuasca use and observed outcomes during (e.g., subjective drug effects) and afterwards (i.e., persisting effects), characterize risks and negative experiences, and describe trauma exposure and personal history. RESULTS/OUTCOMES: Our findings revealed ceremonial use of ayahuasca is associated with significant improvements in mental health, well-being, and psychological functioning, including reductions in depression, anxiety, and shame, and increases in cognitive reappraisal and self-compassion. Most participants reported no lasting adverse effects and experienced notable positive behavioral changes persisting months after ingestion. CONCLUSION/INTERPRETATION: While preliminary, results suggest naturalistic ayahuasca use might hold therapeutic potential for MENA populations exposed to trauma prior to and during the process of migration.

N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic that induces a rapid and transient altered state of consciousness when inhaled or injected via bolus administration. Its marked and novel subjective effects make DMT a powerful tool for the neuroscientific study of consciousness and preliminary results show its potential role in treating mental health conditions. In a within-subjects, placebo-controlled study, we investigated a novel method of DMT administration involving a bolus injection paired with a constant-rate infusion, with the goal of extending the DMT experience. Pharmacokinetic parameters of DMT estimated from plasma data of a previous study of bolus intravenous DMT were used to derive dose regimens necessary to keep subjects in steady levels of immersion into the DMT experience over an extended period of 30 min, and four dose regimens consisting of a bolus loading dose and a slow-rate infusion were tested in eleven healthy volunteers (seven male, four female, mean age ± SD = 37.09 ± 8.93 years). The present method is effective for extending the DMT experience in a stable and tolerable fashion. While subjective effects were maintained over the period of active infusion, anxiety ratings remained low and heart rate habituated within 15 min, indicating psychological and physiological safety of extended DMT. Plasma DMT concentrations increased consistently starting 10 min into DMT administration, whereas psychological effects plateaued into the desired steady state, suggesting the development of acute psychological tolerance to DMT. Taken together, these findings demonstrate the safety and effectiveness of continuous IV DMT administration, laying the groundwork for the further development of this method of administration for basic and clinical research.

Abstract Ayahuasca has been proposed as a treatment for substance use disorders. However, because of its hallucinogenic properties, studies investigating its abuse potential are needed. The aim of the present study was to investigate voluntary ayahuasca drinking in male mice using a two-bottle choice procedure. Male mice were exposed to two bottles, one of water and one of ayahuasca (0.01, 0.03 or 0.1 mg/ml), for 15 h/day, under 3 protocols (acquisition): (1) every other day access; (2) access every 3 days; (3) access every 5 days. Animals were then submitted to a 14-day drug-free period, followed by 3 re-exposure phases (same conditions as during acquisition), with 7 drug-free days between each. Regardless of the ayahuasca concentration, animals showed a preference for ayahuasca over water when exposed to ayahuasca every other day during the acquisition and re-exposure phases. Extending the period between ayahuasca exposures changed the expression of ayahuasca preference, with the longest break (every 5 days) being associated with preference for water over ayahuasca (i.e., ayahuasca aversion), an effect that was more predominantly observed at higher ayahuasca concentrations. A significant interaction was observed between frequency of exposure to ayahuasca and ayahuasca concentration for total ayahuasca intake during the later re-exposure phase. Our findings show that both the frequency of exposure and the ayahuasca concentration are critical when determining ayahuasca preference in a two-bottle choice model in mice, which can help guide therapeutic/ritualistic ayahuasca use.

Ayahuasca is a brew traditionally prepared with a mixture of Psychotria viridis leaves and Banisteriopsis caapi vine and has demonstrated therapeutic properties for depression. Knowledge of the brew composition is important to improve the therapeutic potential and decrease side effects if ayahuasca becomes an option for refractory depression treatment. Ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) was applied to analyze 126 ayahuasca samples collected from different ayahuasqueiro groups and geographic origins. We were able to observe a differentiation in the metabolite composition of ayahuasca samples prepared by diverse ayahuasqueiro groups. These samples presented different antioxidant effects based on FRAP and ORAC assays. Exploratory statistical analysis demonstrated a trend of separating the samples according to the religious group. The most important identified compounds for differentiation of the brew prepared by distinct religious groups are glycosylated and/or phenolic compounds. The comparison based on the mode of ayahuasca preparation presented more variability than the comparison based on the botanical variety of B. caapi used. We conclude that ayahuasca samples prepared with “caupuri” or “tucunacá” separately exhibited differences in the analysis of L-glutamate and the metabolism of arginine and proline. This suggests that a possible variation in this pathway could explain the occurrence of swollen stem nodes in “caupuri,” one of the B. caapi varieties. [ABSTRACT FROM AUTHOR]

Despite increasing interest in psychedelics and their potential therapeutic effects, research on inhaled N,N-Dimethyltryptamine (DMT) remains limited. Inhaled DMT has a reputation for rapid, dramatic onset and a brief duration, but correlates of use frequency remain poorly understood. A sample recruited from relevant internet sites, including nearly 400 people who had inhaled DMT, reported substance use histories, motivations for use, DMT sources, risk perceptions, and other variables. Generally, participants reported initiation motivated by curiosity about DMT’s effects, interest in psychedelics more broadly, and potential spiritual benefits. Those who had used other psychoactive substances (especially ayahuasca) and who had extracted DMT themselves reported inhaled DMT more frequently. Most (>60%) reported obtaining DMT from a friend and claimed it was “slightly difficult” to procure. Participants most commonly inhaled DMT from a glass pipe, in private homes, frequently alone or in small groups. Salient positives associated with inhaling DMT included psychologically cleansing or cathartic experiences. Associated challenges concerned difficult integration, aversive experiences, or “bad trips.” Participants rated DMT as very or slightly safe. These data underscore the need for continued work on this topic to inform education and harm reduction efforts, particularly as the molecule’s reputation for ameliorative effects receives media coverage. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionIn the early twentieth century, ayahuasca gained popularity in northern Brazil, causing political tension due to moral hostility. However, over the course of the century, despite the proscription of DMT and the intensification of the ‘War on Drugs’, three phases of cumulative political gains eventually led to the full regulation of ayahuasca, in 2010. How was this achieved?This paper provides a comprehensive reassessment of the existing literature on ayahuasca in Brazil, utilizing social movement theory. Emphasis is placed on framing methods, or how movements strategically present their aims to particular audiences, in order to effect political change.First, ayahuasca churches constructed a religious frame that emphasized their Christian pedigree. Second, when harassment intensified, ayahuasca was reframed as a charitable endeavour. Finally, in the transition to democracy, the religions added a scientific frame, collaborating with the state to review scientific evidence and establish policy parameters for regulation.Framing ayahuasca as Christian and focusing on charity and science were neither straightforward nor unproblematic, but did allow ayahuasca groups to successfully avoid persecution, establish relationships with powerful actors, and eventually achieve full regulation. This case study provides unique insights into the role of social movements in successful drug policy reform, especially how movements can strategically adapt to and influence prevailing moral codes, resulting in concrete political victories. [ABSTRACT FROM AUTHOR]

Background: In recent years, both meditation and psychedelics have attracted rapidly increasing scientific interest. While the current state of evidence suggests the promising potential of psychedelics, such as psilocybin, to enhance meditative training, it remains equivocal whether these effects are specifically bound to psilocybin or if other classical psychedelics might show synergistic effects with meditation practice. One particularly promising candidate is N,N -dimethyltryptamine (DMT), an active ingredient of ayahuasca. Aim: This study aims to investigate the effect of the psychedelic substance DMT, combined with the monoamine oxidase inhibitor harmine (DMT-harmine), on meditative states, compared to meditation with a placebo. Method: Forty experienced meditators (18 females and 22 males) participated in a double-blind, placebo-controlled study over a 3-day meditation retreat, receiving either placebo or DMT-harmine. Participants' levels of mindfulness, compassion, insight, and transcendence were assessed before, during, and after the meditation group retreat, using psychometric questionnaires. Results: Compared to meditation with a placebo, meditators who received DMT and harmine self-attributed greater levels of mystical-type experiences, non-dual awareness, and emotional breakthrough during the acute substance effects and, when corrected for baseline differences, greater psychological insight 1 day later. Mindfulness and compassion were not significantly different in the DMT-harmine group compared to placebo. At 1-month follow-up, the meditators who received DMT and harmine rated their experience as significantly more personally meaningful, spiritually significant, and well-being-enhancing than the meditators who received placebo. Conclusion: Investigating the impact of DMT-harmine on meditators in a naturalistic mindfulness group retreat, this placebo-controlled study highlights the specific effects of psychedelics during meditation. Trial registration: ClinicalTrials.gov identifier NCT05780216. [ABSTRACT FROM AUTHOR]

Background: Harmine is a component of the hallucinogenic brew, Ayahuasca, which also contains the psychoactive compound, N, N -dimethyltryptamine. Whether pharmaceutical-grade harmine hydrochloride (HCl) has psychoactive effects, the doses at which these might occur, and the dose-response relationship to side effects and safety in humans are unknown. Methods: We conducted a Phase 1, open-label single ascending dose trial in healthy adults with normal body mass index and no prior psychiatric illness. The primary goal was to determine the maximum tolerated dose (MTD) of oral pharmaceutical-grade harmine HCl and to characterize safety and tolerability. A secondary goal was to ascertain whether any oral dose has psychoactive effects. Results: Thirty-four adult participants, aged 18–55 years, were screened for study eligibility. Twenty-five participants met eligibility criteria and were randomized to a single dose of 100, 200, 300, or 500 mg of harmine HCl, respectively, using a continuous reassessment method. The most common adverse events (AEs) observed were gastrointestinal and/or neurological, dose-related, and of mild to moderate severity. The MTD was determined to be between 100 and 200 mg and is weight-based, with 90% of those participants receiving >2.7 mg/kg experiencing a dose-limiting toxicity. No serious AEs of harmine HCl were identified. Conclusions: Harmine HCl can be orally administered to healthy participants in doses <2.7 mg/kg with minimal or no AEs. Doses >2.7 mg/kg are associated with vomiting, drowsiness, and limited psychoactivity. This study is the first to systematically characterize the psychoactive effects of pharmaceutical quality harmine in healthy participants. [ABSTRACT FROM AUTHOR]

The potent hallucinogen N,N-dimethyltryptamine (DMT) has garnered significant interest in recent years due to its profound effects on consciousness and its therapeutic psychopotential. DMT is an integral (but not exclusive) psychoactive alkaloid in the Amazonian plant-based brew ayahuasca, in which admixture of several β-carboline monoamine oxidase A (MAO-A) inhibitors potentiate the activity of oral DMT, while possibly contributing in other respects to the complex psychopharmacology of ayahuasca. Irrespective of the route of administration, DMT alters perception, mood, and cognition, presumably through agonism at serotonin (5-HT) 1A/2A/2C receptors in brain, with additional actions at other receptor types possibly contributing to its overall psychoactive effects. Due to rapid first pass metabolism, DMT is nearly inactive orally, but co-administration with β-carbolines or synthetic MAO-A inhibitors (MAOIs) greatly increase its bioavailability and duration of action. The synergistic effects of DMT and MAOIs in ayahuasca or synthetic formulations may promote neuroplasticity, which presumably underlies their promising therapeutic efficacy in clinical trials for neuropsychiatric disorders, including depression, addiction, and post-traumatic stress disorder. Advances in neuroimaging techniques are elucidating the neural correlates of DMT-induced altered states of consciousness, revealing alterations in brain activity, functional connectivity, and network dynamics. In this comprehensive narrative review, we present a synthesis of current knowledge on the pharmacology and neuroscience of DMT, β-carbolines, and ayahuasca, which should inform future research aiming to harness their full therapeutic potential. [ABSTRACT FROM AUTHOR]

There has been a resurgence of interest in the use of psychedelic therapies for several mental and substance use disorders. Psilocybin, a "classic" serotonergic psychedelic, has emerged as one of the primary compounds of interest in clinical research. While research on psilocybin's potential mental health benefits has grown, data on the safety and efficacy of other serotonergic psychedelics remain limited. A comprehensive scoping review on the use of mescaline, ibogaine, ayahuasca, N,N-dimethyltryptamine (DMT), and lysergic acid diethylamide (LSD) in the treatment of mental and substance disorders was conducted. Independent reviewers screened titles, abstracts, and full texts and conducted data extraction. Seventy-seven studies met the inclusion criteria. There were 43 studies of LSD, 24 studies of ayahuasca, 5 studies of DMT, 5 studies of ibogaine, and 5 studies of mescaline. Commonly reported benefits included improved mood and anxiety symptoms, improved insight, reduced substance use, improved relationships, and decreased vegetative symptoms. Commonly reported adverse effects were psychological, neurological, physical, and gastrointestinal in nature. Serious adverse events (homicide and suicide) were reported in published studies of LSD. In conclusion, there is only low-level evidence to support the safety and efficacy of non-psilocybin serotonergic psychedelics in individuals with mental and substance use disorders. [ABSTRACT FROM AUTHOR]

Copyright of Actualités Pharmaceutiques is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Motivated by multiple factors collectively related to what is often termed the Psychedelic Renaissance, people increasingly consume psychedelics for recreational, medicinal, psychotherapeutic, and even spiritual or religious reasons. In the broader psychedelic ecosystem, ayahuasca (a psychoactive "tea" made from plants indigenous to the Amazon jungle) is becoming one of the more popular psychoactive substances. Ayahuasca churches, retreat centers, and informal "circles" are forming in multiple countries around the world; however, many people who want to drink ayahuasca travel to or near the Amazon, where they seek what they deem an authentic shamanic ayahuasca experience. The lure of authenticity draws people to the Amazon, where they encounter a rather diverse ayahuasca ecosystem. The limited historical and archaeological data suggest that this diversity predates colonialism; however, various factors including the tourists themselves are now agents of change. [ABSTRACT FROM AUTHOR]

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 β‐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. Ayahuasca is a psychoactive beverage from the Amazon, originally prepared from the leaves of Psychotria viridis and the stem of Banisteriopsis caapi. It contains the hallucinogenic N,N‐dimethyltryptamine. In this study, three extraction techniques (DLLME, MEPS, and QuEChERS) were studied. The QuEChERS technique proved to be the most effective in extracting the analytes (60%–88%). The proposed method was optimized and validated following international guidelines. This is the first QuEChERS method for the quantification of ayahuasca constituents. [ABSTRACT FROM AUTHOR]

Graphical Abstract

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.

Ayahuasca has gained the attention of researchers over the past decade as psychedelic-assisted therapy for MDMA and psilocybin have progressed through FDA approved clinical trials. In spite of the increase in research, there are relatively few clinical studies of ayahuasca and little qualitative research on the therapeutic or healing uses of psychedelics in general. The present study included 41 Western participants who were interviewed about their participation in facilitated group ayahuasca experiences (e.g., in shamanic, neoshamanic, spiritual, and religious settings). Participants were interviewed about their intentions for participating, along with the perceived impact of the experiences. In particular, we focused on impacts that participants perceived to be sustained and enduring. We identified an impressive range of beneficial impacts, including improvements in areas that are often a focus of psychotherapy, such as mental health and substance use, health behaviors, interpersonal relationships, sense of self, attitude. Extratherapeutic effects were also observed in areas such as changes in creativity, somatic sensations, physical health/pain, sense of connection to nature, spirituality, and concern for the greater good. Two participants also reported problematic experiences, apparently related to set and setting. Implications for research and practice, along with a humanistic framework for interpreting these findings is provided. [ABSTRACT FROM AUTHOR]

The opioid epidemic and limited access to treatment for opioid withdrawal (OW) and opioid use disorder (OUD) has led individuals to seek alternative treatments. This narrative review aims to educate clinicians on the mechanisms of action, toxicity, and applications of psychoactive plant-based substances patients may be using to self-treat OUD and OW. We specifically discuss ayahuasca, ibogaine, and kratom as they have the most evidence for applications in OUD and OW from the last decade (2012-2022). Evidence suggests these substances may have efficacy in treating OW and OUD through several therapeutic mechanisms including their unique pharmacodynamic effects, rituals performed around ingestion, and increased neuroplasticity. The current evidence for their therapeutic application in OUD and OW is primarily based on small observational studies or animal studies. High-quality, longitudinal studies are needed to clarify safety and efficacy of these substances in treatment of OW and OUD. [ABSTRACT FROM AUTHOR]

The psychedelic beverage ayahuasca is originally obtained by Banisteriopsis caapi (B. caapi) (BC) and Psychotria viridis (P. viridis) (PV). However, sometimes these plant species are replaced by others that mimic the original effects, such as Mimosa hostilis (M. hostilis) (MH) and Peganum harmala (P. harmala) (PH). Its worldwide consumption and the number of studies on its potential therapeutic effects has increased. This study aimed to evaluate the anticancer properties of ayahuasca in human colorectal adenocarcinoma cells. Thus, the maximum inhibitory concentration (IC50) of decoctions of MH, PH, and a mixture of these (MHPH) was determined. The activities of caspases 3 and 9 were evaluated, and the cell proliferation index was determined through immunocytochemical analysis (Ki-67). Two fluorescent probes were used to evaluate the production of oxidative stress and the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) was also evaluated. It was demonstrated that exposure to the extracts significantly induced apoptosis in Caco-2 cells, while decreasing cell proliferation. MH and MHPH samples significantly reduced oxidative stress and significantly increased glutathione peroxidase activity. No significant differences were found in SOD activity. Overall, it was demonstrated that the decoctions have a potential anticancer activity in Caco-2 cells. [ABSTRACT FROM AUTHOR]

Background: In recent years, there has been a growing interest in the therapeutic potential of classical psychedelics like ayahuasca for mental health improvement. Naturalistic studies at ayahuasca retreats have shown (short-term) improvements in mental well-being but understanding the psychological mechanisms is crucial. We are interested in psychological processes such as resilience, self-compassion, and personality traits. Additionally, it is unclear whether changes are solely due to ayahuasca or influenced by the social setting. To address this, a control group participating in a breathwork session, similar to ayahuasca retreats, was included. Methods: In this observational study, individuals who attended an ayahuasca retreat (n = 69) and individuals who participated in a breathwork session (n = 30) completed an online survey one week before (baseline) and one, six, and twelve weeks after they entered the retreat/session. The survey included a series of questionnaires, i.e., the World Health Organisation-Five Well-Being Index, 14-item Resilience Scale, Self-Compassion Scale–Short Form, and Big Five Inventory-10. A linear mixed model (LMM) was used to analyze the outcome data. Results: It was shown that well-being, resilience, and self-compassion increased and remained stable over 12 weeks compared to baseline, regardless of group (ayahuasca or breathwork). Older participants generally reported higher resilience and self-compassion. Self-compassion was also higher in the ayahuasca group overall. Neuroticism decreased in both groups, with lower scores in the ayahuasca group. Agreeableness increased over time, also not influenced by group membership, while there were no changes in extraversion, conscientiousness, or openness. Discussion: Both interventions improved well-being, aligning with prior research. Importantly, this study unveils a novel finding: both interventions enhance resilience and self-compassion for up to three months, offering promise for conditions marked by low well-being, resilience, and self-compassion like depression and anxiety-related disorders. While acknowledging its limitations (e.g., self-selected sample, no specific information of the ayahuasca brew or the breathwork technique), it emphasizes the need for controlled studies with control groups, attention to social contexts in research on these interventions, and to assess other variables like depth of altered states of consciousness that might explain improvement in psychological processes and wellbeing. [ABSTRACT FROM AUTHOR]

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Intense interest surrounds current research on psychedelics, particularly regarding their potential in treating mental health disorders. Various studies suggest a link between the subjective effects produced by psychedelics and their therapeutic efficacy. Neuroimaging evidence indicates an association of changes in brain functional connectivity with the subjective effects of psychedelics. We conducted a review focusing on psychedelics and brain functional connectivity. The review focused on four psychedelic drugs: ayahuasca, psilocybin and LSD, and the entactogen MDMA. We conducted searches in databases of MEDLINE, Embase, APA PsycInfo and Scopus from inception to Jun 2023 by keywords related to functional connectivity and psychedelics. Using the PRISMA framework, we selected 24 articles from an initial pool of 492 for analysis. This scoping review and analysis investigated the effects of psychedelics on subjective experiences and brain functional connectivity in healthy individuals. The studies quantified subjective effects through psychometric scales, revealing significant experiences of altered consciousness, mood elevation, and mystical experiences induced by psychedelics. Neuroimaging results indicated alterations in the functional connectivity of psychedelics, with consistent findings across substances of decreased connectivity within the default mode network and increased sensory and thalamocortical connectivity. Correlations between these neurophysiological changes and subjective experiences were noted, suggesting a brain network basis of the psychedelics' neuropsychological impact. While the result of the review provides a potential neural mechanism of the subjective effects of psychedelics, direct clinical evidence is needed to advance their clinical outcomes. Our research serves as a foundation for further exploration of the therapeutic potential of psychedelics. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: In recent years, there has been a growing interest in the therapeutic potential of classical psychedelics like ayahuasca for mental health improvement. Naturalistic studies at ayahuasca retreats have shown (short-term) improvements in mental well-being but understanding the psychological mechanisms is crucial. We are interested in psychological processes such as resilience, self-compassion, and personality traits. Additionally, it is unclear whether changes are solely due to ayahuasca or influenced by the social setting. To address this, a control group participating in a breathwork session, similar to ayahuasca retreats, was included. Methods: In this observational study, individuals who attended an ayahuasca retreat (n = 69) and individuals who participated in a breathwork session (n = 30) completed an online survey one week before (baseline) and one, six, and twelve weeks after they entered the retreat/session. The survey included a series of questionnaires, i.e., the World Health Organisation-Five Well-Being Index, 14-item Resilience Scale, Self-Compassion Scale–Short Form, and Big Five Inventory-10. A linear mixed model (LMM) was used to analyze the outcome data. Results: It was shown that well-being, resilience, and self-compassion increased and remained stable over 12 weeks compared to baseline, regardless of group (ayahuasca or breathwork). Older participants generally reported higher resilience and self-compassion. Self-compassion was also higher in the ayahuasca group overall. Neuroticism decreased in both groups, with lower scores in the ayahuasca group. Agreeableness increased over time, also not influenced by group membership, while there were no changes in extraversion, conscientiousness, or openness. Discussion: Both interventions improved well-being, aligning with prior research. Importantly, this study unveils a novel finding: both interventions enhance resilience and self-compassion for up to three months, offering promise for conditions marked by low well-being, resilience, and self-compassion like depression and anxiety-related disorders. While acknowledging its limitations (e.g., self-selected sample, no specific information of the ayahuasca brew or the breathwork technique), it emphasizes the need for controlled studies with control groups, attention to social contexts in research on these interventions, and to assess other variables like depth of altered states of consciousness that might explain improvement in psychological processes and wellbeing.

Background: Refugees and immigrants can experience complex stressors from the process of immigration that can have lasting and severe long-term mental health consequences. Experiences after ayahuasca ingestion are shown to produce positive effects on psychological wellbeing and mental health, including anecdotal reports of improved symptoms of trauma and related disorders. However, data on the longitudinal health impact of naturalistic ayahuasca use in Middle Eastern and North African (MENA) immigrant and refugee populations is limited. Aims: The current longitudinal online survey study was conducted to gather prospective data on ceremonial ayahuasca use in a group (N = 15) of primarily female MENA immigrants and refugees and to provide further insight into the patterns and outcomes surrounding that use. The study sought to assess selfreported changes in physical and mental health, well-being, and psychological functioning, examine relationships between aspects of individual mindset (e.g., psychedelic preparedness) prior to ayahuasca use and observed outcomes during (e.g., subjective drug effects) and afterwards (i.e., persisting effects), characterize risks and negative experiences, and describe trauma exposure and personal history. Results/Outcomes: Our findings revealed ceremonial use of ayahuasca is associated with significant improvements in mental health, well-being, and psychological functioning, including reductions in depression, anxiety, and shame, and increases in cognitive reappraisal and self-compassion. Most participants reported no lasting adverse effects and experienced notable positive behavioral changes persisting months after ingestion. Conclusion/Interpretation: While preliminary, results suggest naturalistic ayahuasca use might hold therapeutic potential for MENA populations exposed to trauma prior to and during the process of migration. [ABSTRACT FROM AUTHOR]

In recent years, policymakers have proposed and implemented regulatory changes promoting the deprioritization, decriminalization, or state-level legalization of one or more psychedelic substances, usually referencing data from clinical trials as reasons to support liberalizing drug control policies. As psychedelic policies continue to be drafted, personal possession limits may be considered for inclusion in those regulations. If "allowable amount" limits are to be written into law to set personal possession limits, then such amounts should be more consistently related to psychedelic doses found to be safe and efficacious in clinical trials, existing data on moderate-high doses commonly used in various naturalistic settings, and the few studies that estimate psychedelic dose equivalence based on the intensity of subjective effects. In this commentary, we provide an evidence-informed table of typical moderate-high doses for seven commonly used psychedelic substances. These estimates of comparable moderate-high doses can be used to inform "allowable amount" values for psychedelic substances. When such limits are written into legislation, the adoption of evidence-informed comparable limits akin to those presented here would be an important first step toward ensuring greater parity and consistency in drug policy, relative to limits that have little or no scientific basis. [ABSTRACT FROM AUTHOR]

The global use of certain classical psychedelics has increased in recent years, but little is known about their spectrum of toxicity within Australia. We aim to describe calls to New South Wales Poisons Information Centre relating to exposures to classical psychedelics including lysergic acid diethylamide, psilocybin, N,N-dimethyltryptamine, ayahuasca, mescaline and ibogaine. This is a retrospective observational study of calls to New South Wales Poisons Information Centre between January 2014 and December 2022. We identified exposures to classical psychedelics within New South Wales Poisons Information Centre database and measured the annual number of exposures, source of call (hospital, health care worker, member of the public), co-ingested substances, clinical features and advice given. There were 737 calls related to relevant psychedelic exposures; 352 (47.8 per cent) to lysergic acid diethylamide, 347 (47.0 per cent) to psilocybin, 28 (3.8 per cent) to N,N-dimethyltryptamine, 4 (0.5 per cent) to ayahuasca, 4 (0.5 per cent) to mescaline and 2 (0.3 per cent) to ibogaine. Cases were predominantly male (77.2 per cent) and aged between 20 and 74 years (65.6 per cent). Psychedelic calls more than doubled from 45 in 2014 to 105 in 2022 and 625 (85 per cent) of all calls were either from or referred to hospital. Co-ingestion of psychedelics with another substance occurred in 249 (33.8 per cent) of calls and the most frequent clinical features related to single substance psychedelic exposures were hallucinations (27.6 per cent), gastrointestinal symptoms (21.7 per cent) and tachycardia (18.1 per cent). Seizures occurred in 2.9 per cent of single substance psychedelic exposures. Increasing incidence of psychedelic exposure calls, including those reporting significant toxicity, likely reflects increasing community use. This may in part be driven by increasing interest in psychedelic assisted psychotherapy trials subsequently increasing public awareness. Relatively high poisoning severity contrasts with safety within clinical trials of psychedelic assisted psychotherapy that may relate to the uncontrolled nature of community use which is mitigated within clinical trial environments. Education about safe use may be useful. [ABSTRACT FROM AUTHOR]

Recent research into so-called psychedelic substances, such as psilocybin, ketamine, and mescaline analogues, has been hailed as a "renaissance" heralding a "paradigm shift" in psychiatry. There is hope that psychedelic-assisted therapy will be made more available to address mental and substance use health problems through existing systems of medicalization and legalization. There are important relational and epistemic concerns that must be addressed, however, before we might begin stewarding this class of substances into the medical landscape in a responsible, evidence-based manner. In this paper, we draw on our ethnographic and clinical research observations to argue that the ontological and relational commitments of traditional medicine (ayahuasca-related healing) and randomized controlled trial (RCT) (ketamine-assisted psychotherapy) practices have important and revealing overlaps; together, they bring attention to ideal ways of working with these substances, as well as to ideal forms of healthcare more generally, with implications for reimagining our healthcare system from the ground up. As such, more is needed than a circumscribed shift to a new epistemological orientation ("paradigm"). We conclude by promoting ideals in alignment with our data and observations—relationality, inter-being, and epistemological fluidity—and by exploring how these ideals might reshape the medical landscape. [ABSTRACT FROM AUTHOR]

Objective: This study aims to provide an overview of pharmacological trials that examine the neurocognitive effects of psychedelics among healthy individuals and patients with post-traumatic stress disorder (PTSD) or major depressive disorder (MDD). Methods: The Preferred Reporting Items for Systematic Reviews (PRISMA) was used as a guide to structure and report the findings for this review. A literature search included the MEDLINE database up until December 2022. We included randomized or open-label human studies of MDMA, psilocybin, mescaline, LSD, DMT, or cannabis reporting non-emotionally charged neurocognitive outcomes ("cold cognition") measured through validated neuropsychological tests. Results: A total of 43 full-text papers on MDMA (15), cannabis (12), LSD (6), psilocybin (9), DMT/ayahuasca (1), and mescaline (0) were included, mostly on healthy subjects. A single article on MDMA's effects on cognition in subjects with PTSD was included; there were no studies on psychedelics and neurocognition in MDD. Most of the studies on healthy subjects reported detrimental or neutral effects on cognition during the peak effect of psychedelics with a few exceptions (e.g., MDMA improved psychomotor function). Performance on the type of neurocognitive dimension (e.g., attention, memory, executive function, psychomotor) varies by type of psychedelic, dosage, and cognitive testing. Conclusions: Small samples and a lack of uniformed methods across studies preclude unequivocal conclusions on whether psychedelics enhance, decrease, or have no significant effect on cognitive performance. It is foreseen that psychedelics will soon become an available treatment for various psychiatric disorders. The acute and long-term effects on cognition caused by psychedelics should be assessed in future studies. [ABSTRACT FROM AUTHOR]

The human brain is an extraordinarily complex organ responsible for all aspects of cognition and control. Billions of neurons form connections with thousands of other neurons, resulting in trillions of synapses that create a vast and intricate network. This network is subjected to continuous remodeling that adapts to environmental and developmental changes. The resulting neuroplasticity is crucial to both healthy states and many forms of mental illness and neurodegeneration. This narrative review comprehensively examines N,N-dimethyltryptamine (DMT), a naturally occurring hallucinogen and psychedelic compound, focusing on its implications in promoting neuroplasticity via neuritogenesis. We examine DMT's pharmacology, including its interaction with serotonergic, sigma-1, and trace amine-associated receptors and their associated signaling pathways. The therapeutic potential of DMT in both animal models and clinical trials is discussed with impacts on perception, cognition, emotion, and consciousness. We uniquely focus on current directions centered on unveiling the direct mechanisms of DMT's therapeutic effects that demonstrate transformative effects on mental well-being, particularly for conditions like depression, anxiety, and post-traumatic stress disorder. We discuss the connection between DMT and neuroplasticity, offering the potential for forming new neural connections, improving learning, memory, and aiding recovery from brain injuries, including neurorehabilitation and neuroregeneration. The ultimate potential of DMT's therapeutic efficacy to enhance neurogenesis, especially for neurodegenerative conditions, is also discussed. [ABSTRACT FROM AUTHOR]

Information behaviour is a very productive research area in information science, although some study contexts are still little explored, such as religious and spiritual practices, particularly related to minority religions. Thus, this study investigated the information behaviour of religious leaders of Santo Daime, a religion originating in the Brazilian Amazon. Exploratory research with a qualitative approach and semi-structured interviews with four leaders of the doctrine were carried out. The most used sources of information were documents about the Daime religion, personal experience, contact with other leaders and the institution. Information was sought to guide the participants in their rituals, solve administrative problems, improve their knowledge and strengthen their faith. Used in a critical, reflective and creative way, it seeks coherence with the Daimist principles. The findings may contribute to the understanding of the information behaviour of this little-studied social group and the appreciation of cultural and religious diversity in society. [ABSTRACT FROM AUTHOR]

Qualitative studies and anecdotal reports suggest that experiences with ayahuasca, a psychedelic brew found in Central and South America, may be followed by individuals enduringly feeling more grateful and connected to nature. Yet, to date, these changes have been understudied. Here, participants (N = 54) completed validated surveys related to gratitude, nature relatedness, and nature appreciation one-week before, one-week after, and one-month after attending an ayahuasca retreat center. Compared to baseline, there was a significant increase in gratitude, nature relatedness, and nature appreciation at the one-week and one-month follow-ups. Ratings of mystical-type experiences and awe, but not ego dissolution, during participants’ ayahuasca sessions were weakly-to-moderately correlated with these increases. The number of ayahuasca ceremonies attended at the retreat was not related to change in outcomes, underscoring the importance of the quality rather than the quantity of the experiences in post-acute change. Lastly, participant age was negatively related to the occurrence of mystical-type experiences and awe, supporting literature indicating blunted psychedelic effects with increased age. In the context of study limitations, the results suggest that mystical-type experiences and awe occasioned by ayahuasca may be linked to prosocial changes in gratitude and relationships with nature that may be beneficial to mental health. [ABSTRACT FROM AUTHOR]

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.

Ayahuasca geleneksel olarak Amazon havzasındaki yerli topluluklar tarafından manevi, tıbbi ve şamanik amaçlarla yüzyıllardır kullanılan psikoaktif bir içecektir. Ayahuasca kelimesi tipik olarak hem bitkinin kendisine (Banisteriopsis caapi) hem de diğer bitkilerle birleştirildiğinde elde edilen ve genellikle psikedelik bileşik DMT (dimetiltriptamin) içeren içeceği ifade etmektedir. Ayahuascadaki ana bileşen harmin ve diğer MAO inhibitörlerini içeren Banisteriopsis caapi asmasıdır. Bu inhibitörler DMT’nin ağızdan alındığında emilmesini ve aktif olmasını sağlamaktadır. DMT çeşitli bitkilerde ve hatta insan vücudunda küçük miktarlarda bulunan güçlü bir halüsinojenik bileşiktir. DMT, ayahuasca asmasından elde edilen MAO inhibitörleri ile birleştiğinde aktif hale gelmekte ve genellikle derin iç gözlemsel, manevi/ruhsal ve bazen zorlayıcı olarak tanımlanan yoğun vizyoner deneyimler üretmektedir. Bu yönüyle yerli halklar ayahuascanın ruhlar dünyasıyla ve atalarının ruhlarıyla iletişim kurmalarına, manevi iç görü kazanmalarına olanak tanıyan güçlü bir araç olduğuna inanmaktadır. Genellikle manevi alemden rehberlik, bilgelik, kehanet ve şifa amaçlı kullanılmaktadır. Bunun yanı sıra ayahuasca ritüelleri insanları bir araya getiren toplumsal etkinliklerdir. Deneyimlerini paylaştıkça, birbirlerini destekledikçe ve şamanların bilgeliğinden faydalandıkça katılımcıların topluluk içindeki bağları güçlenmektedir. Törenler ayrıca kültürel geleneklerin ve öğretilerin genç nesillere aktarılmasına da yardımcı olmaktadır. Dolayısıyla ayahuasca yerli kimliğinin korunmasına hizmet eden bir vasıta olarak nitelendirilmektedir. Tüm bu yönleriyle ayahuasca Amazon Havzası’ndaki yerli toplumların dokusuna girift bir şekilde dokunmuş kültürel miras simgesi olarak görülmektedir. 19. yüzyıla gelindiğinde başta Amazon kauçuk patlaması olmak üzere birtakım olaylar ayahuasca kullanımının yerel/kültürel sınırları dışına çıkmasına neden olmuştur. Kauçuk işçilerinin evlerine dönüşlerinden bir müddet sonra da bölgedeki kentlerde senkretik ayahuasca inançları ortaya çıkmaya başlamıştır. 20. yüzyıla geldiğimizde ise Yerli gelenekleriyle Batılı uygulamalar arasındaki kültürel alışverişi kolaylaştıran küreselleşmenin etkisiyle senkretik ayahuasca inançları Amerika, Avrupa ve hatta Asya’nın birçok ülkesinde tezahür etmeye başlamıştır. Senkretik ayahuasca kiliselerinin yanı sıra vizyonlar aracılığıyla derin deneyimler ve iç görüler uyandırma konusundaki rolü nedeniyle maneviyat ve bilinç keşfinin alternatif biçimlerini arayan insanlar tarafından da ayahuasca kullanımına günümüzde oldukça rağbet gösterilmektedir. Bu noktada önemli bir husus gittikçe artan popülaritesiyle birlikte ayahuasca kullanımının uluslararasılaşması onu uyuşturucu yasaları ile karşı karşıya getiren bir dizi problem de ortaya çıkarmıştır. Nitekim ayahuasca günümüz modern yasal çerçeveleri bağlamında içerdiği halüsinojenik bileşik DMT’nin (dimetiltriptamin) varlığından dolayı narkotik maddeler başlığında da değerlendirilmektedir. Bu ikili durum ayahuascanın ağırlıklı olarak kültürel bir miras olarak mı yoksa narkotik bir uyuşturucu olarak mı sınıflandırılması gerektiğine dair sorgu ve tartışmaları da beraberinde getirmiştir. Tartışmanın bir tarafında yer alan devletlere göre uluslararası sözleşmeler gereği bu bitki narkotik kapsamında değerlendirilerek kullanımı dünya çapında yasaklanmalı veya kısıtlanmalıdır. Öte yandan antropologlara göre ise ayahuasca uyuşturucu bir madde olarak değil kültürel bir miras nazarıyla değerlendirilmeli ve buna dayalı bir muameleye tabi tutulmalıdır. Bu noktada uyuşturucu kontrolünün savunucuları yasa dışı narkotikleri engellemeyi amaçlayan uluslararası anlaşmalara bağlı kalma zorunluluğunun altını çizerken; kültürel mirasın savunucuları yerel hak ve gelenekleri korumanın gerekliliğini vurgulamaktadır. Bu çalışma ile amacımız kültürel miras ve narkotik sınıflandırma arasında karmaşık bir kavşakta bulunan ayahuasca hakkındaki tartışmaları uluslararası ilaç sözleşmeleri ile bunlara karşı çeşitli eleştiriler yönelten antropologların görüşleri çerçevesinde ele alıp incelemektir. Bu çerçevede araştırmamızda öncelikle ayahuascanın yerel/kültürel sınırları dışına çıkış süreci ile ilgili kısaca bilgi verilecektir. Ardından uluslararası uyuşturucu madde kullanımı yasaları ile ayahuasca üzerinde uzmanlaşmış antropologların fikirleri çerçevesinde bu bitkinin kullanımı etrafında şekillenen tartışmalar ele alınarak değerlendirilecektir. Ayahuasca kullanımının ülkemiz dahil olmak üzere dünya çapında gittikçe artan popüleritesine karşın konu hakkındaki tartışmalarla ilgili yeterli sayıda ve derinlikte çalışma bulunmaması bizi bu araştırmaya yönlendiren en önemli etkendir. Dolayısıyla bu çalışma ile alanımızın literatürüne önemli bir katkıda bulunmayı ummaktayız.

Survey-based studies suggest naturalistic psychedelic use provides mental health benefits similar to those observed in clinical trials. The current study sought to confirm these findings in a large group of psychedelic users and to conduct a novel examination of associations between amount of psychedelic use and behavioral outcomes, as well as frequency of harms ascribed to psychedelic use. A cross-sectional, online survey was completed by 2,510 adults reporting at least one lifetime psychedelic experience. Participants retrospectively completed a battery of instruments assessing depression, anxiety, and emotional well-being prior to and following psychedelic exposure. Participants also reported preferred psychedelic agent, number of uses, and harms attributed to psychedelic use. Psychedelic use was associated with significant improvements in depressive and anxious symptoms and with increased emotional well-being. These improvements increased in magnitude with increasing psychedelic exposure, with a ceiling effect. However, improvements were noted following a single lifetime use. Strong evidence for benefit of one preferred psychedelic agent over another was not observed, but enduring increases in factors related to mystical-experience and prosocial perspective taking associated with enhanced mental health. Thirteen percent of the survey sample (n = 330) endorsed at least one harm from psychedelic use, and these participants reported less mental health benefit. Results from the current study add to a growing database indicating that psychedelic use-even outside the context of clinical trials-may provide a wide range of mental health benefits, while also posing some risk for harm in a minority of individuals.

BackgroundRefugees and immigrants can experience complex stressors from the process of immigration that can have lasting and severe long-term mental health consequences. Experiences after ayahuasca ingestion are shown to produce positive effects on psychological wellbeing and mental health, including anecdotal reports of improved symptoms of trauma and related disorders. However, data on the longitudinal health impact of naturalistic ayahuasca use in Middle Eastern and North African (MENA) immigrant and refugee populations is limited.AimsThe current longitudinal online survey study was conducted to gather prospective data on ceremonial ayahuasca use in a group (N = 15) of primarily female MENA immigrants and refugees and to provide further insight into the patterns and outcomes surrounding that use. The study sought to assess self-reported changes in physical and mental health, well-being, and psychological functioning, examine relationships between aspects of individual mindset (e.g., psychedelic preparedness) prior to ayahuasca use and observed outcomes during (e.g., subjective drug effects) and afterwards (i.e., persisting effects), characterize risks and negative experiences, and describe trauma exposure and personal history.Results/OutcomesOur findings revealed ceremonial use of ayahuasca is associated with significant improvements in mental health, well-being, and psychological functioning, including reductions in depression, anxiety, and shame, and increases in cognitive reappraisal and self-compassion. Most participants reported no lasting adverse effects and experienced notable positive behavioral changes persisting months after ingestion.Conclusion/InterpretationWhile preliminary, results suggest naturalistic ayahuasca use might hold therapeutic potential for MENA populations exposed to trauma prior to and during the process of migration.

O aumento de casos de depressão na população mundial leva ao questionamento sobre a eficácia dos tratamentos farmacológicos e fomenta a busca por tratamentos alternativos. Estudos a respeito da ayahuasca e seus efeitos na depressão vêm sendo realizados. Por meio de uma revisão integrativa, a partir da questão norteadora: “Quais são os efeitos da ayahuasca em indivíduos com depressão?”, neste estudo buscou-se: (1) identificar potenciais usos terapêuticos do chá de ayahuasca; (2) analisar as características de segurança e riscos à saúde no seu uso; (3) investigar se o contexto do uso influencia seus efeitos. A busca de artigos foi realizada nas bases BVS e PubMed, produzidos entre 2017-2022, resultando em 8 artigos para análise. Os estudos evidenciaram efeitos antidepressivos advindos das interações neuroquímicas e das experiências psicológicas por meio da ayahuasca e apresentaram que a segurança e potencial terapêutico estão atrelados ao contexto de uso e à dosagem ingerida do chá.

Background: There is growing scientific evidence for the therapeutic benefits of the Amazonian plant-based psychedelic "ayahuasca" for neuropsychiatric disorders such as depression and anxiety. However, there are certain challenges when incorporating botanical ayahuasca into biomedical research and clinical therapy environments. Formulations inspired by ayahuasca, which contain specific and standardized active components, are a potential remedy. Methods: We investigated subjective acute and persisting effects of a novel formulation containing the reversible monoamine oxidase inhibitor harmine (orodispersible tablet containing 100 mg MAO-I) and N,N-dimethyltryptamine (incremental intranasal dosing of up to 100 mg DMT), compared with two other conditions, namely harmine alone and placebo, in a crossover RCT in 31 healthy male subjects. Results: DMT + harmine, but not harmine alone, induced a psychedelic experience assessed with the 5D-ASC rating scale [global score: F(2,60) = 80.21, p < 0.001] and acute experience sampling items over time, characterized by psychological insights [PIQ, F(2,58.5) = 28.514, p < 0.001], emotional breakthroughs [EBI, F(2,60) = 26.509, p < 0.001], and low scores on the challenging experience questionnaire [CEQ, F(2,60) = 12.84, p < 0.001]. Participants attributed personal and spiritual significance to the experience (GSR) with mainly positive persisting effects (PEQ) at 1- and 4-months follow-up. Acute drug effects correlated positively with persisting effects. We found no changes in trait measures of personality, psychological flexibility, or general well-being, and no increases in psychopathology (SCL-90-R) were reported. Discussion and Conclusion: Our results suggest that the experience induced by the standardized DMT + harmine formulation induces a phenomenologically rich psychedelic experience, demonstrates good psychological safety and tolerability, is well tolerated, and induces beneficial psychological processes that could possibly support psychotherapy. Further studies are required to investigate the psychotherapeutic potential in patients. [ABSTRACT FROM AUTHOR]

Classic psychedelics, including lysergic acid diethylamide (LSD), psilocybin, mescaline, N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), are potent psychoactive substances that have been studied for their physiological and psychological effects. However, our understanding of the potential interactions and outcomes when using these substances in combination with other drugs is limited. This systematic review aims to provide a comprehensive overview of the current research on drug–drug interactions between classic psychedelics and other drugs in humans. We conducted a thorough literature search using multiple databases, including PubMed, PsycINFO, Web of Science and other sources to supplement our search for relevant studies. A total of 7102 records were screened, and studies involving human data describing potential interactions (as well as the lack thereof) between classic psychedelics and other drugs were included. In total, we identified 52 studies from 36 reports published before September 2, 2023, encompassing 32 studies on LSD, 10 on psilocybin, 4 on mescaline, 3 on DMT, 2 on 5-MeO-DMT and 1 on ayahuasca. These studies provide insights into the interactions between classic psychedelics and a range of drugs, including antidepressants, antipsychotics, anxiolytics, mood stabilisers, recreational drugs and others. The findings revealed various effects when psychedelics were combined with other drugs, including both attenuated and potentiated effects, as well as instances where no changes were observed. Except for a few case reports, no serious adverse drug events were described in the included studies. An in-depth discussion of the results is presented, along with an exploration of the potential molecular pathways that underlie the observed effects. [ABSTRACT FROM AUTHOR]