Search Results (41)

Pain is a protective mechanism that can be classified into acute and chronic types. Ayahuasca is a psychoactive brew rich in dimethyltryptamine or DMT (a 5-HT_2A receptor agonist), and harmine (a monoamine-oxidase (MAO) inhibitor) used for religious and therapeutic purposes. Previous preclinical and anecdotal evidence suggests that ayahuasca and its compounds have antinociceptive and anti-inflammatory effects due to 5-HT_2A agonism and MAO inhibition. Thus, the current study aims to provide a systematic review of the antinociceptive and anti-inflammatory effects of ayahuasca and its alkaloids in preclinical models. All studies published up to December 2024 were screened and evaluated for eligibility. A total of 1535 publications were identified, of which 29 adhered to the predefined criteria. Reviewed articles reported antinociceptive effects of ayahuasca, harmine, and harmaline. Regarding anti-inflammatory effects, the compounds of ayahuasca, especially harmine, have demonstrated a reduction and an increase in pro-inflammatory and anti-inflammatory cytokines, respectively. Although there are promising results regarding the antinociceptive and anti-inflammatory effects of ayahuasca and its alkaloids, further investigation is needed. Full article

Banisteriopsis is a genus in the Malpighiaceae family with 61 species, notable for including ritualistic taxa such as B. caapi (Spruce ex Griseb.) C.V. Morton, one of the main components of Ayahuasca tea. We analyzed 38 Banisteriopsis species, representing more than 60% of the genus, to investigate its geographical origin, diversification period, and colonization routes in the Neotropics. Plastid genes (matK, ndhF, and rbcL) and nuclear regions (ETS, ITS, and PHYC) were used in our analyses. Divergence time analyses were performed using Bayesian inference with a relaxed molecular clock and ancestral area reconstruction. Our results show that Banisteriopsis originated in the Miocene approximately 22 million years ago, and its diversification coincides with the expansion of dry areas in South America. Banisteriopsis began colonizing the Cerrado earlier than most other plants, and the history of the genus reveals that the biome served as a source of species for Neotropical rainforests. Our results also indicate a probable ancient origin for B. caapi, with no evidence of human manipulation in its diversification, and they reinforce archaeological evidence of a millennia-old exchange of uses among Amazonian peoples. Full article

Objective: To provide a state of the art on the use, role, and function of music during psychedelic-assisted therapy (PAT) with ayahuasca. Introduction: Ayahuasca is a medicinal brew with psychoactive qualities used by indigenous communities throughout the Amazon region, and music is deemed crucial during ayahuasca experiences. In PAT, music forms part of the set and setting, but it lacks systematization and is poorly explored in the scientific literature. Inclusion criteria: Published literature in English, Spanish, and Portuguese, focusing on conceptualizing, defining, or describing the use, role, and/or function of music in PAT sessions with ayahuasca. Methods: This review follows the JBI methodology for scoping reviews. We will search Web of Science, Scopus, Google Scholar, and PubMed databases without year restrictions, and a hand search of articles will be performed. Two reviewers will assess titles/abstracts, followed by independent reviews of included full texts. An Excel data extraction sheet will be used to tabulate the information. The findings will be presented narratively, including respective tables or figures. If feasible, a potential theoretical framework for the use, role, and function of music during PAT with ayahuasca will be outlined, including implications for future research and clinical practice. Full article

Accumulating psychedelic research has demonstrated a potential for improving mental health and wellbeing, yet studies in the context of eating disorders (EDs) are limited. This study aims to explore the subjective effects of psychedelic experiences to gain insight into the benefits and risks for people with EDs. Semi-structured interviews were conducted with eight adults aged 25–54 (mean age = 36.9), reporting to have had experiences with EDs and psychedelics in both naturalistic and clinical settings. Participants had multiple diagnoses and suffered chronic EDs, (mean age of onset = 13), diagnosed (N = 7) and undiagnosed (N = 1). Reports of cessation or the reduction of ED symptoms were unanimous and long-lasting for seven, with two participants reporting recovery attributed to psychedelic use. Two participants reported relapsing, attributed to environmental factors in the months following. Thematic analysis resulted in two superordinate themes, each comprising three subordinate themes. The first superordinate theme, ‘Exploring’ via the ‘gateway to healing’, illustrates mental, emotional, and transcendental elements of psychedelic experiences. The second superordinate theme, ‘Transformation’ and being ‘able to do the work’, illustrates cognitive and behavioural outcomes, with retrospective safety perceptions. These findings may provide more in-depth information on what benefits and experiences people with EDs can obtain from the use of psychedelic drugs and may inform more robust investigations of psychedelic-assisted therapy for the treatment of EDs. Full article

Diplopterys pubipetala (Malpighiaceae) is a liana native to the Brazilian Cerrado biome, traditionally used in Ayahuasca preparations. Despite its cultural importance, research on its chemical composition and biological activities, which may have therapeutic potential, is limited. This study investigated the volatile and non-volatile secondary metabolites of D. pubipetala leaves, their antioxidant capacity, and their antibacterial and antifungal activities. Volatile compounds were identified using gas chromatography-mass spectrometry (GC-MS) coupled to solid-phase microextraction (SPME), while non-volatile compounds were annotated using UHPLC-MS/MS-ESI-Q-TOF. Antioxidant capacity was evaluated by DPPH assay, and antimicrobial activity was assessed in vitro against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida species (C. albicans, C. tropicalis, C. glabrata). GC-MS analysis revealed 25 predominant volatile compounds, including ethyl dodecanoate, ethyl tetradecanoate, nonanoic acid, and 5-methylhexan-2-one, with documented antifungal, antioxidant, and antimicrobial activities. The crude extract and ethyl acetate fraction showed strong antioxidant capacity (EC₅₀ 9.83 µg/mL and 6.42 µg/mL, respectively), and antifungal effects were observed against Candida species. This study provides the first comprehensive investigation of the antioxidant capacity and antibacterial and antifungal activities of D. pubipetala, together with a detailed chemical profile of its volatile compounds. Full article

Background and Objectives: Substance use disorders (SUDs) affect millions worldwide. Despite increasing drug use, treatment options remain limited. Psychedelic-assisted therapy (PAT), integrating psychedelic substances with psychotherapy, offers a promising alternative by addressing underlying neural mechanisms. Materials and Methods: This review’s purpose is to investigate the current understanding of psychedelic therapy for treating SUDs, including tobacco, alcohol, and drug addiction. The systematic review approach focused on clinical trials and randomized controlled trials conducted from 2013 to 2023. The search was performed using PubMed, Google Scholar, and Consensus AI, following PRISMA guidelines. Studies involving psychedelics like LSD, psilocybin, ibogaine, and ayahuasca for treating various addictions were included, excluding naturalistic studies and reviews. Results: Our results highlight the key findings from 16 clinical trials investigating psychedelic therapy for SUDs. Psychedelics like psilocybin and ayahuasca showed promise in reducing alcohol and tobacco dependence, with psilocybin being particularly effective in decreasing cravings and promoting long-term abstinence. The studies revealed significant improvements in substance use reduction, especially when combined with psychotherapy. However, the variability in dosages and study design calls for more standardized approaches. These findings emphasize the potential of psychedelics in SUD treatment, though further large-scale research is needed to validate these results and develop consistent protocols. Conclusions: This research reviewed the past decade’s international experience, emphasizing the growing potential of psychedelic therapy in treating SUDs pertaining to alcohol, tobacco, and cocaine dependence. Psychedelics such as psilocybin and ketamine can reduce cravings and promote psychological well-being, especially when combined with psychotherapy. However, regulatory barriers and specialized clinical training are necessary to integrate these therapies into mainstream addiction treatment safely. Psychedelics offer a promising alternative for those unresponsive to conventional methods. Full article

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

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

Because psychedelics have been found to increase psychological traits like openness, mental flexibility, and interpersonal perceptiveness, some researchers believe that psychedelics could help individuals cope with the psychological effects of discrimination. However, it is still unclear whether psychedelic use can help manage the internalized stigma that deters formal mental health treatment. This study investigates the impact of six measures of psychedelic use (MDMA, psilocybin, DMT, ayahuasca, peyote/mescaline, and LSD) on psychological distress (Kessler Psychological Distress Scale) and internalized stigma. The study used data from the National Survey of Drug Use and Health (NSDUH) from 2008 to 2019, with a sample size of 458,372 participants. Ordinary least square regression models were conducted using Stata 18. Gender analysis found that among men, ayahuasca use was linked to reduced stigma perception associated with higher distress. For women, DMT use was linked to reduced stigma perceptions when experiencing higher distress. However, results find that individuals who have used MDMA and psilocybin reported heightened perceptions of stigma associated with increased psychological distress. Among women, MDMA and psilocybin use was associated with a higher perception of stigma when they experienced distress. These findings suggest that, overall, psychedelics may not reduce the impact of distress on the perception of stigma, especially for women. Full article

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. Full article

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. Full article

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. Full article

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. Full article

Auricular acupuncture (AA) has been used to manage chemotherapy-induced nausea and vomiting (CINV). However, the application of the technique varies widely among the clinical trials that test its effectiveness. The aim of the present study was to develop and clinically validate an AA protocol for the management of CINV in cancer patients. This study was carried out in two stages: (1) development of the AA protocol for the management of CINV and (2) clinical validation of the protocol. The content validity of the protocol was determined by a panel of specialists, with an agreement rate ranging from 85.7% to 100%. In the clinical validation, when administered to cancer patients, the protocol developed has been shown to reduce the incidence, frequency, severity, and length of nausea and vomiting following chemotherapy, as well as the severity of nausea and anticipatory nausea following chemotherapy. This protocol needs to be tested in future studies, including a pilot study with a sham group and a randomized clinical trial, in order to further evaluate its feasibility, acceptability, safety, and clinical usefulness for the management of CINV. Full article

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). Full article