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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.

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]

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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]

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]

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: 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]

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.

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.

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]

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]

Background: The classical psychedelics psilocybin, peyote, ayahuasca/ N, N-dimethyltryptamine, and lysergic acid diethylamide can temporarily produce altered states of consciousness, characterized by changes in sensory perception, thought, mood, and the sense of self-reality and meaning. It is important to have reliable instruments for quantifying these altered states in trials, due to a plausible link between the acute subjective experience and treatment outcome. Methods: We conducted a review of outcome measures applied in research on classical psychedelics to assess one or more dimensions of the acute subjective psychedelic experience. Three relevant databases were searched electronically. Two reviewers independently conducted article selection and data extraction regarding the instruments, dimensions, geography, population, and psychedelic substance investigated in the included studies. We identified the five most utilized instruments for the most recent 6 years, as well as the five most utilized instruments for each psychedelic. Results: We included 93 papers, which reported on 93 unique trials and utilized 17 different rating scales. Of these, the most utilized were the Five-Dimensional Altered States of Consciousness Questionnaire, visual analog or Likert scales specially developed for the trials, the Hallucinogen Rating Scale, the States of Consciousness Questionnaire, and the Abnormer Psychischer Zustand. Discussion: Considerable variability was found in the instruments utilized in clinical trials on classical psychedelics. We advise and encourage the development of a core outcome set for psychedelic research to enable altered state comparisons across compounds, participants, and settings. We further advise that instruments be designed to assess the "setting" of a psychedelic experience. [ABSTRACT FROM AUTHOR]

Music and psychedelics have been intertwined throughout the existence of Homo sapiens, from the early shamanic rituals of the Americas and Africa to the modern use of psychedelic‐assisted therapy for a variety of mental health conditions. Across such settings, music has been highly prized for its ability to guide the psychedelic experience. Here, we examine the interplay between music and psychedelics, starting by describing their association with the brain's functional hierarchy that is relied upon for music perception and its psychedelic‐induced manipulation, as well as an exploration of the limited research on their mechanistic neural overlap. We explore music's role in Western psychedelic therapy and the use of music in indigenous psychedelic rituals, with a specific focus on ayahuasca and the Santo Daime Church. Furthermore, we explore work relating to the evolution and onset of music and psychedelic use. Finally, we consider music's potential to lead to altered states of consciousness in the absence of psychedelics as well as the development of psychedelic music. Here, we provide an overview of several perspectives on the interaction between psychedelic use and music—a topic with growing interest given increasing excitement relating to the therapeutic efficacy of psychedelic interventions. [ABSTRACT FROM AUTHOR]

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Introduction: Despite an emerging understanding regarding the pivotal mechanistic role of subjective experiences that unfold during acute psychedelic states, very little has been done in the direction of better characterizing such experiences and determining their long-term impact. The present paper utilizes two cross-sectional studies for spotlighting -- for the first time in the literature -- the characteristics and outcomes of self-reported past experiences related to one's subjective sense of death during ayahuasca ceremonies, termed here Ayahuasca-induced Personal Death (APD) experiences. Methods: Study 1 (n = 54) reports the prevalence, demographics, intensity, and impact of APDs on attitudes toward death, explores whether APDs are related with psychopathology, and reveals their impact on environmental concerns. Study 2 is a larger study (n = 306) aiming at generalizing the basic study 1 results regarding APD experience, and in addition, examining whether APDs is associated with self-reported coping strategies and values in life. Results: Our results indicate that APDs occur to more than half of those participating in ayahuasca ceremonies, typically manifest as strong and transformative experiences, and are associated with an increased sense of transcending death (study 1), as well as the certainty in the continuation of consciousness after death (study 2). No associations were found between having undergone APD experiences and participants' demographics, personality type, and psychopathology. However, APDs were associated with increased self-reported environmental concern (study 1). These experiences also impact life in profound ways. APDs were found to be associated with increases in one's self-reported ability to cope with distress-causing life problems and the sense of fulfillment in life (study 2). Discussion: The study's findings highlight the prevalence, safety and potency of death experiences that occur during ayahuasca ceremonies, marking them as possible mechanisms for psychedelics' long-term salutatory effects in nonclinical populations. Thus, the present results join other efforts of tracking and characterizing the profound subjective experiences that occur during acute psychedelic states. [ABSTRACT FROM AUTHOR]

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.

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.

Background: Anxiety disorders are commonly diagnosed and cause substantial functional impairment. A mixture of pharmaco)logic and psychosocial treatments currently exists, but these treatments are not always tolerable and effective. For patients with anxiety resistant to standard therapy, psychedelics may be a promising alternative. This review assesses the therapeutic benefits and safety of psychedelics in treating anxiety disorders. Methods: We searched PubMed, Embase, PsycInfo, and CINAHL for clinical trials investigating psychedelics in patients with clinician-diagnosed generalized anxiety disorder, social anxiety disorder, specific phobia, separation anxiety disorder, selective mutism, panic disorder, agoraphobia, and anxiety attributable to another medical condition. We analyzed data from 9 indepen)dent psychedelic-assisted trials testing ayahuasca (1 study), ketamine (4 studies), lysergic acid diethylamide (LSD) (2 studies), 3,4- methylenedioxymethamphetamine (MDMA) (1 study), and psilocybin (1 study). Efficacy was assessed by measuring the change in outcome measures and the quality of life from baseline. Results: The reviewed studies demonstrated encouraging efficacy in reducing anxiety symptoms, increasing self-perception, and increasing social function in patients with generalized anxiety disorder, social anxiety disorder, or anxiety attributable to another medical condition while establishing feasibility and evidence of safety. For many patients, the therapeutic effects of the psychedelic treatment lasted weeks, and no severe adverse events were reported. Conclusion: Based on the evidence of symptom reduction and safety, the current literature (2011 to 2021) shows that psychedelics could be considered for treating clinician-diagnosed anxiety disorders. Psychedelics may provide an alternative therapeutic option for patients resistant to current standard treatments. [ABSTRACT FROM AUTHOR]

Ayahuasca is a hallucinogenic plant used throughout South America for religious, cultural and healing ceremonies. Previous studies have analysed it as a therapy method from either the microperspective, such as physiological and psychological effects of substance use, or the macroperspective, such as legal issues or cultural appropriation of ayahuasca by Westerners. There is a need to combine those two aspects to fully understand the effects of ayahuasca for therapists and clients in Western communities. By utilising an autoethnographic instrumental case study, we discuss the possible risk of ayahuasca gaining popularity in Western societies without an understanding of how the social context plays a tremendous part in healing using this method. We also discuss the risk of intrapsychic experiences brought about by ayahuasca that may deter individuals from seeking appropriate treatment. It is not our intention to present ayahuasca as an illegitimate or invalid method of healing; rather, we emphasise the importance of integrating micro‐ and macroperspectives in psychotherapy practice. We suggest that the metacognitive counselling approach be taken by both clients and therapists when adopting indigenous methods of therapy which may add a significantly positive effect. Although we hope this study offers realistic and lived experiences to generate pragmatic solutions for therapists and clients, we recognise that it is necessary to collect data from a larger number of both clients and therapists to better support our suggestion of the metacognitive counselling approach. [ABSTRACT FROM AUTHOR]

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 centres. Practitioners and ayahuasca centres are left with navigating globalized concepts of mental health and ethics while attempting to remain authentic to local ontologies of healing, care, and safety. [ABSTRACT FROM AUTHOR]

Background: In the context of increasing scientific interest in the potential therapeutic use of psychedelic agents and their underlying psychotherapeutic mechanisms, we undertake the first detailed assessment of insights and life and lifestyle changes associated with ayahuasca consumption. Methods: An international cross-sectional study of ayahuasca drinkers in a variety of settings was performed (n = 8907). Bivariate analysis and multivariate linear and logistic regressions were used to explore associations between a range of covariates and insights, life changes and lifestyle changes. The least absolute shrinkage and selection operator variable selection method (LASSO) was used to select the variables most relevant for inclusion in models assessing broader wellbeing and mental health associations. Results: Insights are almost universally reported as part of the ayahuasca experience and are highly valued by drinkers and strongly predictive of subsequent beneficial life and lifestyle changes. A range of personal, vocational, religious/spiritual and health-related life changes (attributed to ayahuasca) are also commonly identified, as are various beneficial lifestyle and health behavior changes. Demographic and ayahuasca drinking variables that are predictive of such phenomena are reported, along with associations between insights, life and lifestyle changes and perceived growth in psychological wellbeing and current mental health status (Kessler 10 and SF-12 MCS). Conclusion: Insights and subsequent life and lifestyle changes appear to have a central role in the transformative effects reported by individuals consuming ayahuasca, with these occurring across contexts of use and demographic groups. [ABSTRACT FROM AUTHOR]

As the research field with psychedelic substances grows, it is expected to encompass a more extensive cohort of individuals presenting a spectrum of medical conditions, comorbidities, and unique physiological traits, thereby increasing the likelihood of potential adverse events. Furthermore, it is worth noting that there is a scarcity of the specialized literature regarding procedures to ensure the safe management of clinical trials involving psychedelics. Acknowledging this, our research team designed a series of protocols to standardize the care and management of adverse scenarios, ensuring the safety and well-being of research volunteers included in clinical trials conducted by the LEAPS (Laboratory for Studies with Hallucinogens and Psychedelics in Mental Health, linked to the University of São Paulo). These guidelines have been meticulously crafted based on the established guideline philosophy of Hospital das Clínicas de Ribeirão Preto (the university hospital of Universidade de São Paulo), consultation with specialists in the field, and a thorough review of the existing literature. The process resulted in protocols that have been tailored to specifically address the unique requirements and particularities of clinical research with psychedelic substances (in this case, ayahuasca and ibogaine). As a result, these guidelines aim to cover a range of potential issues, encompassing both psychiatric manifestations (e.g., panic attacks, suicidal behavior, and psychotic episodes) and clinical manifestations (e.g., hypertensive crisis and hypoglycemia). [ABSTRACT FROM AUTHOR]

Alcohol is the recreational drug most frequently consumed, and its high frequency of use can lead to worsening social, psychological, and domestic issues. The age group most susceptible to alcohol dependence is 18- to 24-year-old youths, demanding interventional tools to target early involvement risks. Ayahuasca seems to be a promising therapeutic tool since evidence suggests it presents potential for the treatment of depression, anxiety, and substance abuse, among other disorders. This study aimed to analyze subjective reports of university students with harmful alcohol use participating in a single-blind study evaluating the effects of one ayahuasca dose (1 mL/kg). Twenty-one days after ayahuasca administration, semi-structured interviews were conducted (n = 6) to identify peer psychological elements linked to its therapeutic potential. Subsequently, content analysis methodology was employed to define the main categories: Self-perception of experience, Positive Impacts (PI), Substances Use Pattern (SUP), Insights (I), Visual Effects, Transient Derealization, and Sleep Pattern. Among these, the most pertinent categories for this study were PI, SUP, and I, as, together, they suggest a potential link between insights and/or positive emotions and reduced alcohol consumption due to their internal transformation potential, which could be linked to a decrease in consumption. [ABSTRACT FROM AUTHOR]

This paper describes three case studies from an outpatient intercultural therapeutic program founded and run by Yaqui health professionals and traditional healers to serve members of the Yaqui tribe residing in Sonora, Mexico. This pilot therapeutic program has been designed specifically for Indigenous individuals, incorporating the ceremonial use of naturally derived psychedelics in addressing substance use disorders and other mental health issues. The program employs a community-based approach, integrating various traditional Indigenous healing practices like the sweatlodge (temazcal), medicinal plant preparations, and the ritualistic use of selected psychedelics from natural sources (such as ayahuasca, peyote, and secretions from Incilius alvarius). These approaches are complemented by culturally attuned group and individual psychotherapy sessions, as well as group sports, community meals, collaborative construction efforts for a permanent clinical infrastructure, and cultural engagements such as art, crafts, and collective music. To evaluate the program's efficacy, safety, and cultural implications, an ongoing observational study is being conducted by an international team of researchers. The preliminary results demonstrate therapeutic progress and improved psychometric outcomes observed in the three case studies presented, indicating promise for this intercultural therapeutic intervention. [ABSTRACT FROM AUTHOR]

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

Renewed interest in psychedelic substances in the 21st century has seen the exploration of psychedelic treatments for various psychiatric disorders including substance use disorder (SUD). This review aimed to assess the effectiveness of psychedelic treatments for people with SUD and those falling below diagnostic thresholds (i.e. substance misuse). We systematically searched 11 databases, trial registries, and psychedelic organization websites for empirical studies examining adults undergoing psychedelic treatment for SUD or substance misuse, published in the English language, between 2000 and 2021. Seven studies investigating treatment using psilocybin, ibogaine, and ayahuasca, alone or adjunct with psychotherapy reported across 10 papers were included. Measures of abstinence, substance use, psychological and psychosocial outcomes, craving, and withdrawal reported positive results, however, this data was scarce among studies examining a wide range of addictions including opioid, nicotine, alcohol, cocaine and unspecified substance. The qualitative synthesis from three studies described subjective experience of psychedelic-assisted treatments enhanced self-awareness, insight, and confidence. At present, there is no sufficient research evidence to suggest effectiveness of any of the psychedelics on any specific substance use disorder or substance misuse. Further research using rigorous effectiveness evaluation methods with larger sample sizes and longer-term follow-up is required. [ABSTRACT FROM AUTHOR]

For veterans with moral conflicts brought on by war work, evidence-based approaches designed for posttraumatic stress disorder tend not to attend to resulting spiritual and ethical forms of suffering. These "treatment-resistant" veterans are at high risk for self-harm. While new medical treatments are being developed, it is also clear that veterans themselves are experimenting in collective, ritualistic, and community-based ceremonial uses of psychedelic medicine. This article introduces the concept of altered states of combat (ASCombat) to refer to the specific mind-set soldiers experience in combat. As a preliminary analytical framework, we associate ASCombat to the widely studied altered states of consciousness as a way to advance understanding on the use and effectiveness of psychedelics and collective healing in the veteran population. The notion of ASCombat and typology is grounded in 4 years of veteran-engaged research in community-based healing approaches. The self-report of one case, by the veteran author of this article, provides suggestive materials for analysis, discussion, and future research. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

There has recently been a resurgence of interest in psychedelic compounds based on studies demonstrating their potential therapeutic applications in treating posttraumatic stress disorder, substance abuse disorders, and treatment-resistant depression. Despite promising efficacy observed in some clinical trials, the full range of biological effects and mechanism(s) of action of these compounds have yet to be fully established. Indeed, most studies to date have focused on assessing the psychological mechanisms of psychedelics, often neglecting the nonpsychological modes of action. However, it is important to understand that psychedelics may mediate their therapeutic effects through multi-faceted mechanisms, such as the modulation of brain network activity, neuronal plasticity, neuroendocrine function, glial cell regulation, epigenetic processes, and the gut-brain axis. This review provides a framework supporting the implementation of a multi-faceted approach, incorporating in silico, in vitro and in vivo modeling, to aid in the comprehensive understanding of the physiological effects of psychedelics and their potential for clinical application beyond the treatment of psychiatric disorders. We also provide an overview of the literature supporting the potential utility of psychedelics for the treatment of brain injury (e.g., stroke and traumatic brain injury), neurodegenerative diseases (e.g., Parkinson's and Alzheimer's diseases), and gut-brain axis dysfunction associated with psychiatric disorders (e.g., generalized anxiety disorder and major depressive disorder). To move the field forward, we outline advantageous experimental frameworks to explore these and other novel applications for psychedelics. [ABSTRACT FROM AUTHOR]

Introduction: Serotonergic psychedelics such as ayahuasca are reported to promote both structural and functional neural plasticity via partial 5-HT2A agonism. However, little is known about how these molecular mechanisms may extend to repeated psychedelic administration in humans, let alone neuroanatomy. While early evidence suggests localised changes to cortical thickness in long-term ayahuasca users, it is unknown how such findings may be reflected by largescale anatomical brain networks comprising cytoarchitecturally complex regions. Methods: Here, we examined the relationship between cortical gene expression markers of psychedelic action and brain morphometric change following repeated ayahuasca usage, using high-field 7 Tesla neuroimaging data derived from 24 members of an ayahuasca-using church (Santo Daime) and case-matched controls. Results: Using a morphometric similarity network (MSN) analysis, repeated ayahuasca use was associated with a spatially distributed cortical patterning of both structural differentiation in sensorimotor areas and de-differentiation in transmodal areas. Cortical MSN remodelling was found to be spatially correlated with dysregulation of 5-HT2A gene expression as well as a broader set of genes encoding target receptors pertinent to ayahuasca’s effects. Furthermore, these associations were similarly interrelated with altered gene expression of specific transcriptional factors and immediate early genes previously identified in preclinical assays as relevant to psychedelic-induced neuroplasticity. Conclusion: Taken together, these findings provide preliminary evidence that the molecular mechanisms of psychedelic action may scale up to a macroscale level of brain organisation in vivo. Closer attention to the role of cortical transcriptomics in structural-functional coupling may help account for the behavioural differences observed in experienced psychedelic users. [ABSTRACT FROM AUTHOR]

Rationale: The psychedelic effects of the traditional Amazonian botanical decoction known as ayahuasca are often attributed to agonism at brain serotonin 5-HT2A receptors by N,N-dimethyltryptamine (DMT). To reduce first pass metabolism of oral DMT, ayahuasca preparations additionally contain reversible monoamine oxidase A (MAO-A) inhibitors, namely β-carboline alkaloids such as harmine. However, there is lacking biochemical evidence to substantiate this pharmacokinetic potentiation of DMT in brain via systemic MAOA inhibition. Objectives: We measured the pharmacokinetic profile of harmine and/or DMT in rat brain, and tested for pharmacodynamic effects on brain glucose metabolism and DMT occupancy at brain serotonin 5-HT2A receptors. Methods: We first measured brain concentrations of harmine and DMT after treatment with harmine and/or DMT at low sub-cutaneous doses (1 mg/kg each) or harmine plus DMT at moderate doses (3 mg/kg each). In the same groups of rats, we also measured ex vivo the effects of these treatments on the availability of serotonin 5-HT2A receptors in frontal cortex. Finally, we explored effects of DMT and/or harmine (1 mg/kg each) on brain glucose metabolism with [18F]FDG-PET. Results: Results confirmed that co-administration of harmine inhibited the formation of the DMT metabolite indole-3-acetic acid (3-IAA) in brain, while correspondingly increasing the cerebral availability of DMT. However, we were unable to detect any significant occupancy by DMT at 5-HT2A receptors measured ex vivo, despite brain DMT concentrations as high as 11.3 μM. We did not observe significant effects of low dose DMT and/or harmine on cerebral [18F]FDG-PET uptake. Conclusion: These preliminary results call for further experiments to establish the dose-dependent effects of harmine/DMT on serotonin receptor occupancy and cerebral metabolism. [ABSTRACT FROM AUTHOR]

Increasing harvest and overexploitation of wild plants for non‐timber forest products can significantly affect population dynamics of harvested populations. While the most common approach to assess the effect of harvest and perturbation of vital rates is focused on the long‐term population growth rate, most management strategies are planned and implemented over the short‐term.We developed an integral projection model to investigate the effects of harvest on the demography and the short‐ and long‐term population dynamics of Banisteriopsis caapi in the Peruvian Amazon rainforest.Harvest had no significant effect on the size‐dependent growth of lianas, but survival rates increased with size. Harvest had a significant negative effect on size‐dependent survival where larger lianas experienced greater mortality rates under high harvest pressure than smaller lianas. In the populations under high harvest pressure, survival of smaller lianas was greater than that of populations with low harvest pressure. Harvest had no significant effect on clonal or sexual reproduction, but fertility was size‐dependent.The long‐term population growth rates of B. caapi populations under high harvest pressure were projected to decline at a rate of 1.3% whereas populations with low harvest pressure are expected to increase at 3.2%. However, before reaching equilibrium, over the short‐term, all B. caapi populations were in decline by 26% (high harvested population) and (low harvested population) 20.4% per year.Elasticity patterns were dominated by survival of larger lianas irrespective of harvest treatments. Life table response experiment analyses indicated that high harvest caused the 6% reduction in population growth rates by significantly reducing the survival of large lianas and increasing the survival‐growth of smaller lianas including vegetative reproductive individuals.Synthesis and applications. This study emphasizes how important it is for management strategies for B. caapi lianas experiencing anthropogenic harvest to prioritize the survival of larger size lianas and vegetative reproducing individuals, particularly in increased harvested systems often prone to multiple stressors. From an applied conservation perspective, our findings illustrate the importance of both prospective and retrospective perturbation analyses in population growth rates in understanding the population dynamics of lianas in general in response to human‐induced disturbance. [ABSTRACT FROM AUTHOR]

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.