The Effects of Ayahuasca on Psychological Disorders: A Systematic Literature Review.

Ayahuasca is an original Amazonian brew made from the vines and leaves of Psychotroa viridis and Banisteriopsis caapi. Both P. viridis and B. caapi give this brew its unique psychedelic properties which have been revered over centuries. In recent years, ayahuasca has gained attention as a potential therapeutic tool for mental health disorders, including substance abuse and depression. The uniqueness of ayahuasca's therapeutic potential is that it is an amalgamation of its biochemical makeup and the ritual guided by a shaman, along with the interpretation of the participant of their experience. The boom of "ayahuasca tourism" has brought forth testimonies of feeling "cured" of depression, and substance abuse and an improvement in overall well-being. This systematic literature review focuses on summarizing the recently available research on the effectiveness of ayahuasca as a treatment for depression, anxiety, substance abuse, eating disorders, and post-traumatic stress disorder. It also focuses on understanding the effects it has on personality traits that play a significant role in the manifestation of the above-listed mental health conditions effects. Additionally, the review investigates the importance and role the ritual itself plays, often described as the "mystical experience". This systematic literature review aims to explore the current state of knowledge regarding the use of ayahuasca for numerous mental health conditions by analyzing medical research papers published no earlier than September 2017 to no later than May 2023 from Google Scholar and PubMed. A total of 43 articles met the criteria and were used for detailed analysis. This review will synthesize the findings of the studies, examining the potential therapeutic effects of ayahuasca on multiple mental health disorders, the significance of the "mystical experience," and the mechanisms of action underlying its effects. Through the review, ayahuasca proves to be a worthwhile therapeutic tool that if used in the right setting influences mind, body, and spirit. It is important to note that most studies used in this article relied on surveys and self-reporting proving to be a limitation as no clear standard has been achieved to test the efficacy of ayahuasca. The respect for the culture and origin needs to be retained as Western medicine dwells deeper into ayahuasca's benefits.

Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis.

We aim to systematically review and meta-analyze the effectiveness and safety of psychedelics [psilocybin, ayahuasca (active component DMT), LSD and MDMA] in treating symptoms of various mental disorders. Web of Science, Embase, EBSCO, and PubMed were searched up to February 2024 and 126 articles were finally included. Results showed that psilocybin has the largest number of articles on treating mood disorders (N = 28), followed by ayahuasca (N = 7) and LSD (N = 6). Overall, psychedelics have therapeutic effects on mental disorders such as depression and anxiety. Specifically, psilocybin (Hedges' g = -1.49, 95% CI [-1.67, -1.30]) showed the strongest therapeutic effect among four psychedelics, followed by ayahuasca (Hedges' g = -1.34, 95% CI [-1.86, -0.82]), MDMA (Hedges' g = -0.83, 95% CI [-1.33, -0.32]), and LSD (Hedges' g = -0.65, 95% CI [-1.03, -0.27]). A small amount of evidence also supports psychedelics improving tobacco addiction, eating disorders, sleep disorders, borderline personality disorder, obsessive-compulsive disorder, and body dysmorphic disorder. The most common adverse event with psychedelics was headache. Nearly a third of the articles reported that no participants reported lasting adverse effects. Our analyses suggest that psychedelics reduce negative mood, and have potential efficacy in other mental disorders, such as substance-use disorders and PTSD.

Trips Through the Skin: Reviewing Cutaneous Drug Reactions to Psychedelics and Hallucinogens.

Although psychedelic and hallucinogenic substances have gained popularity for therapeutic use, their dermatologic adverse effects are poorly characterized. This review characterizes the cutaneous reactions associated with psychedelic and hallucinogenic drugs. A review of PubMed and Scopus was conducted from the inception of databases to August 31, 2023. Search terms included drug names and classes (cannabis, MDMA, ecstasy, 3,4-methylenedioxymethamphetamine, psychedelics, hallucinogens, peyote, marijuana, lysergic acid diethylamide, LSD, ketamine, dimethyltryptamine, DMT, phencyclidine, PCP, dextromethorphan, psilocybin, and ayahuasca), and dermatosis terms (dermatitis, contact dermatitis, drug eruption, skin reaction, and urticaria). Studies were included if there was an association with a psychedelic or hallucinogenic and any cutaneous reaction; studies without both components were excluded. Twenty-two studies met inclusion criteria, describing reactions to cannabis (10 studies), MDMA (5 studies), ketamine (4 studies), and psilocybin (3 studies). Forty total patients were included. Among cannabis-related reactions, the most common reaction was type I hypersensitivity by topical exposure (n = 21). Three patients reported type IV hypersensitivity reactions to contact with cannabis or cannabis-derived oils, all of whom experienced vesicular contact dermatitis. Two additional patients presented with an erythema-multiforme-like reaction and acute generalized exanthematous pustulosis after systemic administration, respectively. MDMA was associated with acneiform eruptions (2 cases), an urticarial eruption, a guttate psoriasis-like reaction, a fixed drug eruption, and Stevens-Johnson syndrome (1 case). Four patients reported type I hypersensitivity reactions to ketamine. Four patients reported vesicular eruptions, cyanosis, or widespread jaundice to psilocybin. Of the cases, 8 patients had cutaneous reactions that resolved with drug cessation, 10 resolved with cessation plus treatment, and resolution in 7 cases was not reported. Zero studies were found describing other psychedelic or hallucinogenic compounds. Further research is required to characterize reactions and treatments linked to the variety of extant psychedelics and hallucinogens.

A Systematic Review of the Neurocognitive Effects of Psychedelics in Healthy Populations: Implications for Depressive Disorders and Post-Traumatic Stress Disorder.

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.

Solvent-free parallel artificial liquid membrane extraction for drugs of abuse in plasma samples using LC-MS/MS.

BACKGROUND: Parallel artificial liquid membrane extraction (PALME) is a 96-well plate setup variant of liquid-phase microextraction. Basic or acidic analytes are extracted in neutral form from the sample, through a supported liquid membrane (SLM), and into aqueous acceptor. PALME is already considered a green extraction technique, but in the current conceptual work, we sought to make it even greener by replacing the use of organic solvents with essential oils (EO). PALME was combined with LC-MS/MS for analysis of plasma samples and multiple drugs of abuse with toxicological relevance (amphetamines, phenethylamines, synthetic cathinones, designer benzodiazepines, ayahuasca alkaloids, lysergic acid diethylamide, and ketamine). RESULTS: Fourteen EO were compared to organic solvents frequently used in PALME. The EO termed smart & sassy yielded the best analyte recovery for all drugs studied and was thus selected as SLM. Then, factorial screening and Box-Behnken were employed to optimize the technique. The extraction time, concentration of base, sample volume, and percentage of trioctylamine significantly impacted analyte recovery. The optimum values were defined as 120 min, 10 mmol/L of NaOH, 150 µL, and 0%, respectively. Once optimized, validation parameters were 1-100 ng mL-1 as linear range, accuracy ±16.4%, precision >83%, 1 ng mL-1 as limit of quantitation, 0.1-0.75 ng mL-1 as limit of detection, matrix effect <20%, and recovery 20-106%. Additionally, EO purchased from different production batches were tested and achieved acceptable reproducibility. Data were in compliance with requirements set by internationally accepted validation guidelines and the applicability of the technique was proven using authentic samples. SIGNIFICANCE: In this study, the use of an EO provided a solvent-free sample preparation technique suited to extract different classes of drugs of abuse from plasma samples, dismissing the use of hazardous organic solvents. The method also provided excellent sample clean-up, thus being a simple and efficient tool for toxicological applications that is in agreement with the principles of sustainable chemistry.

Psychedelic Therapy: A Primer for Primary Care Clinicians-Historical Perspective and Overview.

BACKGROUND: Psychedelic drugs have recently emerged as plausibly effective pharmacological agents for the management of depression, anxiety, and other neuropsychiatric conditions, including those that are treatment-resistent. The latter half of the 20th century marked a revolution in the treatment of mental illnesses, exemplified by the introduction of selective serotonin reuptake inhibitors and other pharmacological agents. Nevertheless, mental illness remains a major public health crisis, affecting nearly one billion individuals worldwide. AREAS OF UNCERTAINTY: Because of the decades-long status of several psychedelics as Schedule I drugs, there have not been very many large, double-blind, randomized controlled trials of psychedelics. Owing to small sample sizes, there may be rare yet serious adverse events that have not been reported in the clinical trials thus far. THERAPEUTIC ADVANCES: Esketamine, a dissociative hallucinogen drug, was approved for the management of major depressive disorder by the Food and Drug Administration in 2019. As of January 2024, two Phase III trials of 3,4-methylenedioxymethamphetamine (MDMA), a synthetic drug that inhibits the serotonin transporter, have been completed; the results indicate that MDMA is superior to existing pharmacological treatments for post-traumatic stress disorder. A phase III trial of psilocybin, a naturally occurring serotonin receptor partial agonist, is currently underway. The following series details the current state of research in psychedelic therapeutics, including lysergic acid diethylamide (LSD), N-N-dimethyltryptamine (DMT) and ayahuasca, psilocybin, ibogaine, MDMA, and ketamine. LIMITATIONS: While initial clinical trials of psychedelics for depression were very promising, trials of psilocybin with larger sample sizes (100+ participants) suggest that its remission rate is 25%-29%. This is about the same as the remission rate of antidepressants, which is roughly 30% according to the landmark STAR*D trial. CONCLUSIONS: Psychedelic drugs and structural derivatives offer a great deal of promise for the management of a wide range of psychiatric morbidities. It is imperative that clinicians become familiar with these novel agents and learn how to integrate psychedelic therapy with the rest of their care through open communication and referral.

Psychedelic Therapy: A Primer for Primary Care Clinicians-N,N-Dimethyltryptamine and Ayahuasca.

BACKGROUND: N,N-dimethyltryptamine (DMT) is a naturally occurring serotonergic psychedelic found in natural plants around the globe. As the main psychoactive component in ayahuasca, which also contains monoamine oxidase inhibitors, DMT has been consumed as plant-based brew by indigenous peoples for centuries. Further research is required to delineate the therapeutic utility of DMT. AREAS OF UNCERTAINTY: Although previous research has shown that DMT is synthesized endogenously, it may not be produced at physiologically relevant concentrations. Additionally, the phenomenological similarities between the DMT-induced state and near-death experiences led to the popular hypothesis that endogenous DMT is released during the dying process. However, this hypothesis continues to be debated. Generally, DMT and ayahuasca seem to be physiologically and psychiatrically safe, although ayahuasca is known to cause transient vomiting. THERAPEUTIC ADVANCES: A double-blind, randomized controlled trial showed that, within 1 week, ayahuasca causes remission in 36% of patients with treatment-resistant depression. According to top-line results from a recent phase IIa trial, 57% of patients with major depressive disorder experienced remission 12 weeks after receiving a single intravenous dose of DMT. LIMITATIONS: There has only been a single published double-blind randomized controlled trial on ayahuasca and 2 on DMT. All clinical trials have had small sample sizes (≤34 participants). DMT requires further research to understand its therapeutic and clinical potential as a psychedelic. CONCLUSIONS: Preliminary evidence indicates that ayahuasca and DMT may be more effective than existing antidepressants for treating major depressive disorder and treatment-resistant depression.

Ayahuasca-enhanced extinction of fear behaviour: Role of infralimbic cortex 5-HT2A and 5-HT1A receptors.

BACKGROUND AND PURPOSE: Ayahuasca (AYA) is a botanical psychedelic with promising results in observational and small clinical trials for depression, trauma and drug use disorders. Its psychoactive effects primarily stem from N,N-dimethyltryptamine (DMT). However, there is a lack of research on how and where AYA acts in the brain. This study addressed these questions by examining the extinction of aversive memories in AYA-treated rats. EXPERIMENTAL APPROACH: We focused on the 5-HT1A and 5-HT2A receptors, as DMT exhibits a high affinity for both of them, along with the infralimbic cortex in which activity and plasticity play crucial roles in regulating the mnemonic process under analysis. KEY RESULTS: A single oral treatment with AYA containing 0.3 mg·kg-1 of DMT increased the within-session extinction of contextual freezing behaviour without affecting its recall. This protocol, when repeated twice on consecutive days, enhanced extinction recall. These effects were consistent for both 1- and 21-day-old memories in males and females. AYA effects on fear extinction were independent of changes in anxiety and general exploratory activity: AYA- and vehicle-treated animals showed no differences when tested in the elevated plus-maze. The 5-HT2A receptor antagonist MDL-11,939 and the 5-HT1A receptor antagonist WAY-100635 infused into the infralimbic cortex respectively blocked within- and between-session fear extinction effects resulting from repeated oral administration of AYA. CONCLUSION AND IMPLICATIONS: Our findings highlight complementary mechanisms by which AYA facilitates the behavioural suppression of aversive memories in the rat infralimbic cortex. These results suggest potential beneficial effects of AYA or DMT in stress-related disorders.

Effects of Ayahuasca on Gratitude and Relationships with Nature: A Prospective, Naturalistic Study.

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.

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

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

Ayahuasca and its major component harmine promote antinociceptive effects in mouse models of acute and chronic pain.

ETHNOPHARMACOLOGICAL RELEVANCE: Ayahuasca (AYA) is a psychedelic brew used in religious ceremonies. It is broadly used as a sacred medicine for treating several ailments, including pain of various origins. AIM OF THE STUDY: To investigate the antinociceptive effects of AYA and its mechanisms in preclinical models of acute and chronic pain in mice, in particular during experimental neuropathy. MATERIALS AND METHODS: The antinociceptive effects of AYA administered orally were assessed in the following models of pain: formalin test, Complete Freund's Adjuvant (CFA)-induced inflammation, tail flick test, and partial sciatic nerve ligation model of neuropathic pain. Antagonism assays and Fos immunohistochemistry in the brain were performed. AYA-induced toxicity was investigated. AYA was chemically characterized. The antinociceptive effect of harmine, the major component present in AYA, was investigated. RESULTS: AYA (24-3000 µL/kg) dose-dependently reduced formalin-induced pain-like behaviors and CFA-induced mechanical allodynia but did not affect CFA-induced paw edema or tail flick latency. During experimental neuropathy, single treatments with AYA (24-3000 µL/kg) reduced mechanical allodynia; daily treatments once or twice a day for 14 days promoted consistent and sustained antinociception. The antinociceptive effect of AYA (600 µL/kg) was reverted by bicuculline (1 mg/kg) and methysergide (5 mg/kg), but not by naloxone (5 mg/kg), phaclofen (2 mg/kg), and rimonabant (10 mg/kg), suggesting the roles of GABAA and serotonergic receptors. AYA increased Fos expression in the ventrolateral periaqueductal gray and nucleus raphe magnus after 1 h, but not after 6 h or 14 days of daily treatments. AYA (600 µL/kg) twice a day for 14 days did not alter mice's motor function, spontaneous locomotion, body weight, food and water intake, hematological, biochemical, and histopathological parameters. Harmine (3.5 mg/kg) promoted consistent antinociception during experimental neuropathy. CONCLUSIONS: AYA promotes consistent antinociceptive effects in different mouse models of pain without inducing detectable toxic effects. Harmine is at least partially accountable for the antinociceptive properties of AYA.

The Psychedelic Future of Post-Traumatic Stress Disorder Treatment.

Post-traumatic stress disorder (PTSD) is a mental health condition that can occur following exposure to a traumatic experience. An estimated 12 million U.S. adults are presently affected by this disorder. Current treatments include psychological therapies (e.g., exposure-based interventions) and pharmacological treatments (e.g., selective serotonin reuptake inhibitors (SSRIs)). However, a significant proportion of patients receiving standard-of-care therapies for PTSD remain symptomatic, and new approaches for this and other trauma-related mental health conditions are greatly needed. Psychedelic compounds that alter cognition, perception, and mood are currently being examined for their efficacy in treating PTSD despite their current status as Drug Enforcement Administration (DEA)- scheduled substances. Initial clinical trials have demonstrated the potential value of psychedelicassisted therapy to treat PTSD and other psychiatric disorders. In this comprehensive review, we summarize the state of the science of PTSD clinical care, including current treatments and their shortcomings. We review clinical studies of psychedelic interventions to treat PTSD, trauma-related disorders, and common comorbidities. The classic psychedelics psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT) and DMT-containing ayahuasca, as well as the entactogen 3,4-methylenedioxymethamphetamine (MDMA) and the dissociative anesthetic ketamine, are reviewed. For each drug, we present the history of use, psychological and somatic effects, pharmacology, and safety profile. The rationale and proposed mechanisms for use in treating PTSD and traumarelated disorders are discussed. This review concludes with an in-depth consideration of future directions for the psychiatric applications of psychedelics to maximize therapeutic benefit and minimize risk in individuals and communities impacted by trauma-related conditions.

Psychological and physiological effects of extended DMT.

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.

Assessment of the acute subjective psychedelic experience: A review of patient-reported outcome measures in clinical research on classical psychedelics.

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.

Ayahuasca ceremony leaders' perspectives on special considerations for eating disorders.

Eating disorders (EDs) are difficult conditions to resolve, necessitating novel treatments. Ayahuasca, a psychedelic plant medicine originating in Indigenous Amazonian communities, is being investigated. Aspects of ceremonial ayahuasca use (purging, dietary restrictions) appear similar to ED behaviors, raising questions about ayahuasca's suitability as an intervention for individuals with EDs. This study explored the perspectives of ayahuasca ceremony leaders on these and other considerations for ceremonial ayahuasca drinking among individuals with EDs. A qualitative content analysis of interviews was undertaken with 15 ayahuasca ceremony leaders, the majority of whom were from the West/Global North. Screening for EDs, purging and dietary restrictions, potential risks and dangers, and complementarity with conventional ED treatment emerged as categories. The findings offer ideas, including careful screening and extra support, to promote safe and beneficial ceremony experiences for ceremony participants with EDs. More research is needed to clarify the impacts of ceremony-related purging and preparatory diets. To evolve conventional models of treatment, the ED field could consider Indigenous approaches to mental health whereby ayahuasca ceremony leaders and ED researchers and clinicians collaborate in a decolonizing, bidirectional bridging process between Western and Indigenous paradigms of healing.

Psychedelia: The interplay of music and psychedelics.

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.

Drug-drug interactions involving classic psychedelics: A systematic review.

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.

Shared functional connectome fingerprints following ritualistic ayahuasca intake.

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

Safety and tolerability of inhaled N,N-Dimethyltryptamine (BMND01 candidate): A phase I clinical trial.

Psychedelics are being increasingly examined for their therapeutic potential in mood disorders. While the acute effects of ayahuasca, psilocybin, and lysergic acid diethylamide (LSD) last over several hours, inhaled N,N-Dimethyltryptamine (DMT) effects last around 10 min, which might provide a cost- and time-effective alternative to the clinical application of oral psychedelics. We aimed at investigating the safety and tolerability of inhaled DMT (BMND01 candidate). We recruited 27 healthy volunteers to receive a first, lower dose and a second, higher dose (5/20 mg, 7.5/30 mg, 10/40 mg, 12.5/50 mg, or 15/60 mg) of inhaled DMT in an open-label, single-ascending, fixed-order, dose-response study design. We investigated subjective experiences (intensity, valence, and phenomenology), physiological effects (blood pressure, heart rate, respiratory rate, blood oxygen saturation, body temperature), biochemical markers (liver, kidney, and metabolic functions), and adverse events during the acute and post-acute effects of DMT. DMT dose-dependently increased intensity, valence and perceptual ratings. There was a mild, transient, and self-limited increase in blood pressure and heart rate. There were no changes in safety blood biomarkers and no serious adverse events. DMT dose-dependently enhanced subjective experiences and positive valence. Inhaled DMT might be an efficient, non-invasive, safe route of administration, which might simplify the clinical use of this substance. This is the first clinical trial to test the effects of inhaled DMT (BMND01 candidate).