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.

Long-term benefits to psychological health and well-being after ceremonial use of Ayahuasca in Middle Eastern and North African immigrants and refugees.

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.

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.

Ayahuasca e saúde mental: efeitos do seu uso associado a casos de depressão / Ayahuasca and mental health: effects of its use in association with depresion cases / Ayahuasca y salud mental: efectos de sue uso en asociación con casos de depressión

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 (AU).

The increase in cases of depression in the world's population leads to questioning the effectiveness of pharmacological treatments and encourages the search for alternative treatments. Studies about ayahuasca andyour effectsondepressionhavebeenconducted. Guided by the question: "What are the effects of ayahuasca in individuals with depression?" this study was a integrativereview that aimed to: (1) identify potential therapeutic uses of ayahuasca tea;(2) analyzethesafetycharacteristics andhealthrisks inyour use; (3) investigatewhetherthecontextofuseinfluences your effects.The search for articles was conducted in the BVS and PubMed databases, produced between 2017-2022, resulting in 8 articles for analysis. Thestudies showed antidepressanteffectsresultingfromneurochemical interactions andpsychologicalexperiences as results of the use of ayahuasca and showed that the safety and therapeutic potential are linked to the context of use and the ingested dosage of the tea (AU).

El aumento de los casos de depresión en la población mundial lleva a cuestionar la eficacia de los tratamientos farmacológicos y fomenta la búsqueda de tratamientos alternativos. Se han realizado estudios sobre la ayahuasca y sus efectos sobre la depresión. Por medio de la cuestión: "¿Cuáles son los efectos de la ayahuasca en personas con depresión?", este estudio de revisión integrativabuscó: (1) identificar los usos terapéuticos potenciales del té de ayahuasca; (2) analizar las características de seguridad y los riesgos para la salud en su uso; (3) investigar si el contexto de uso influye en sus efectos. La búsqueda de artículos se realizó en las bases de datos BVS y PubMed, producidas entre 2017-2022, resultando 8 artículos para análisis. Fueron observados en los estudios efectos antidepresivos advenidos de la ayahuasca y que la seguridad y potencial terapéutico están vinculados al contexto de uso y la dosis ingerida del té (AU).

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.

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.

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.

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.

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.

Overcoming the clinical challenges of traditional ayahuasca: a first-in-human trial exploring novel routes of administration of N,N-Dimethyltryptamine and harmine.

Recently, the Amazonian plant medicine "ayahuasca"-containing the psychedelic compound N,N-dimethyltryptamine (DMT) and numerous ß-carboline alkaloids, such as harmine-has been suggested to exhibit beneficial effects in patients with affective and other mental health disorders. Although ayahuasca ingestion is considered safe, its pharmacokinetics/pharmacodynamics and tolerability profile pose some challenges and may limit the clinical applicability in vulnerable patient populations. While overdosing and the admixture of intolerable plant constituents may explain some of the common adverse reactions, the peroral route of administration may represent another relevant source of gastro-intestinal intolerabilities and unpredictable pharmacokinetics across users. To overcome these challenges, the present work aimed at creating ayahuasca-analogue formulations with improved pharmacokinetics and tolerability profiles. To this end, we developed peroral formulas and compared them with parenteral formulas specifically designed to circumvent the gastro-intestinal tract. In more detail, peroral administration of a capsule (containing purified DMT and harmine) was tested against a combined administration of an oromucosal harmine tablet and an intranasal DMT spray at two dose levels in an open-label within-subject study in 10 healthy male subjects. Pharmacokinetic and pharmacodynamic profiles were assessed by means of continuous blood sampling, vital sign monitoring, and psychometric assessments. Common side effects induced by traditional herbal ayahuasca such as nausea, vomiting, and diarrhea were significantly attenuated by our DMT/harmine formulations. While all preparations were well tolerated, the combined buccal/intranasal administration of harmine and DMT yielded substantially improved pharmacokinetic profiles, indicated by significantly reduced variations in systemic exposure. In conclusion, the combined buccal/intranasal administration of harmine and DMT is an innovative approach that may pave the way towards a safe, rapid-acting, and patient-oriented administration of DMT/harmine for the treatment of affective disorders. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04716335.

Efficacy and Safety of Psychedelics in Treating Anxiety Disorders.

Background: Anxiety disorders are commonly diagnosed and cause substantial functional impairment. A mixture of pharmacologic 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 independent 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.

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

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

Present and future of metabolic and metabolomics studies focused on classical psychedelics in humans.

Psychedelics are classical hallucinogen drugs that induce a marked altered state of consciousness. In recent years, there has been renewed attention to the possible use of classical psychedelics for the treatment of certain mental health disorders. However, further investigation to better understand their biological effects in humans, their mechanism of action, and their metabolism in humans is needed when considering the development of future novel therapeutic approaches. Both metabolic and metabolomics studies may help for these purposes. On one hand, metabolic studies aim to determine the main metabolites of the drug. On the other hand, the application of metabolomics in human psychedelics studies can help to further understand the biological processes underlying the psychedelic state and the mechanisms of action underlying their therapeutic potential. This review presents the state of the art of metabolic and metabolomic studies after lysergic acid diethylamide (LSD), mescaline, N,N-dimethyltryptamine (DMT) and ß-carboline alkaloids (ayahuasca brew), 5-methoxy-DMT and psilocybin administrations in humans. We first describe the characteristics of the published research. Afterward, we reviewed the main results obtained by both metabolic and metabolomics (if available) studies in classical psychedelics and we found out that metabolic and metabolomics studies in psychedelics progress at two different speeds. Thus, whereas the main metabolites for classical psychedelics have been robustly established, the main metabolic alterations induced by psychedelics need to be explored. The integration of metabolomics and pharmacokinetics for investigating the molecular interaction between psychedelics and multiple targets may open new avenues in understanding the therapeutic role of psychedelics.

Corrigendum: Ceremonial ayahuasca in amazonian retreats-mental health and epigenetic outcomes from a six-month naturalistic study.

[This corrects the article DOI: 10.3389/fpsyt.2021.687615.].

Cortical structural differences following repeated ayahuasca use hold molecular signatures.

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 large-scale 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.