Daniel Perkins’s research while affiliated with Victoria University Melbourne and other places

Chronic pain and mental health issues like depression and anxiety significantly contribute to disease burden in Western countries. While cannabinoids are suggested to have analgesic, anxiolytic and antidepressant properties, evidence, especially for long-term use, is inconclusive. This 12-month observational study evaluated the effects of prescribed medicinal cannabis for 96 patients suffering from pain, as well as sleep disturbances, depression and anxiety. Treatment outcomes for pain, depression, anxiety and sleep problems were assessed at 3, 6, and 12 months using validated instruments. Significant reductions were observed in pain scores and the interference of pain on daily functions, alongside improvements in mental health and sleep. Many patients reported notable improvements in pain severity and reduced use of pain medications in the first 6 months, with a decline at 12 months. Additionally, sustained improvements in depression, anxiety, stress and sleep were observed, with about half reporting substantial improvement. Adverse effects were common but mostly mild or moderate, most commonly dry mouth and sleepiness. These results show that prescribed medicinal cannabis treatment is associated with improvements in chronic pain and mental health symptoms, such as depression, anxiety and stress. However, findings also suggest reduced effectiveness with longer-term use, emphasizing the need for additional research.

Psychedelics have recently re‐emerged as potential treatments for various psychiatric conditions that impose major public health costs and for which current treatment options have limited efficacy. At the same time, personalized medicine is increasingly being implemented in psychiatry to provide individualized drug dosing recommendations based on genetics. This review brings together these topics to explore the utility of pharmacogenomics (a key component of personalized medicine) in psychedelic‐assisted therapies. We summarized the literature and explored the potential implications of genetic variability on the pharmacodynamics and pharmacokinetics of psychedelic drugs including lysergic acid diethylamide (LSD), psilocybin, N,N ‐dimethyltryptamine (DMT), 5‐methoxy‐ N,N ‐dimethyltryptamine (5‐MeO‐DMT), ibogaine and 3,4‐methylenedioxymethamphetamine (MDMA). Although existing evidence is limited, particularly concerning pharmacodynamics, studies investigating pharmacokinetics indicate that genetic variants in drug‐metabolizing enzymes, such as cytochrome P450, impact the intensity of acute psychedelic effects for LSD and ibogaine, and that a dose reduction for CYP2D6 poor metabolizers may be appropriate. Furthermore, based on the preclinical evidence, it can be hypothesized that CYP2D6 metabolizer status might contribute to altered acute psychedelic experiences with 5‐MeO‐DMT and psilocybin when combined with monoamine oxidase inhibitors. In conclusion, considering early evidence that genetic factors can influence the effects of certain psychedelics, we suggest that pharmacogenomic testing should be further investigated in clinical research. This is necessary to evaluate its utility in improving the safety and therapeutic profile of psychedelic therapies and a potential future role in personalizing psychedelic‐assisted therapies, should these treatments become available.

Artificial intelligence (AI) and psychedelic medicines are among the most high‐profile evolving disruptive innovations within mental healthcare in recent years. Although AI and psychedelics may not have historically shared any common ground, there exists the potential for these subjects to combine in generating innovative mental health treatment approaches. In order to inform our perspective, we conducted a scoping review of relevant literature up to late August 2024 via PubMed intersecting AI with psychomedical use of psychedelics. Our perspective covers the potential application of AI in psychedelic medicine for: drug discovery and clinical trial optimization (including pharmacodynamics); study design; understanding psychedelic experiences; personalization of treatments; clinical screening, delivery, and follow‐up (potentially delivered via chatbots/apps); application of psychological preparation, integration, and general mental health support; its role in enhancing treatment via brain modulatory devices (including virtual reality and haptic suits); and the consideration of ethical and security safeguards. Challenges include the need for sufficient data protection and security, and a range of necessary ethical protections. Future avenues of exploration could involve directly administering psychedelics (or providing algorithm‐generated effects) to inorganic AI‐interfaced neural networks that may exceed human brain activity (i.e., cognitive capacity) and intelligence.

Indigenous Amazonian shamanic ayahuasca practice is embedded in a nature-based context and is employed as an ecological mediating agent and in collective environmental decision-making processes by some of the groups that use it. Phenomenologically, the ayahuasca experience is often rich in nature-based themes and content, and its usage has been associated with eliciting shifts in perspectives and attitudes towards nature. In this proof-of-concept study, participation in an ayahuasca retreat in a traditional Indigenous Amazonian context (with a mean of 6.31 ceremonies attended) was associated with significant increases in nature relatedness directly following ayahuasca retreats as assessed via the Short form Nature Relatedness Scale (NR-6) and The Extended Inclusion of Nature in Self scale (EINS), and improvements in depression and stress as assessed via the Depression, Anxiety and Stress Scale (DASS-21) were also found, but not on the anxiety subscale. Furthermore, a significant negative correlation with moderate effect size was found between changes in nature-relatedness and stress, suggesting that an increase in nature relatedness is associated with decreased stress levels after attending Amazonian ayahuasca retreats in our sample. It is currently unclear if the changes seen were due to consumption of the ayahuasca brew, participation in ceremony, or the retreat setting itself. Although this pilot study suggests a potential therapeutic role for Amazonian ayahuasca retreats as a multidimensional intervention, further work is required to assess the role of possible mediators underlying such shifts, while evaluating to what extent these are sustained for long term.

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.

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.

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

Ayahuasca is a psychedelic plant brew originating from the Amazon rainforest. It is formed from two basic components, the Banisteriopsis caapi vine and a plant containing the potent psychedelic dimethyltryptamine (DMT), usually Psychotria viridis. Here we review the history of ayahuasca and describe recent work on its pharmacology, phenomenological responses, and clinical applications. There has been a significant increase in interest in ayahuasca since the turn of the millennium. Anecdotal evidence varies significantly, ranging from evangelical accounts to horror stories involving physical and psychological harm. The effects of the brew on personality and mental health outcomes are discussed in this review. Furthermore, phenomenological analyses of the ayahuasca experience are explored. Ayahuasca is a promising psychedelic agent that warrants greater empirical attention regarding its basic neurochemical mechanisms of action and potential therapeutic application.

Ayahuasca is an Amazonian psychoactive plant medicine being explored for its potential therapeutic uses in Western contexts. Preliminary studies link ayahuasca use with improvements across a range of mental health indicators, but studies have not yet explored qualitative aspects of the post-treatment process known in the psychedelic literature as "integration". This includes how participants make sense of their ayahuasca experiences and minimise harm/maximise benefits after ayahuasca use. A global online survey, conducted between 2017 and 2019, collected responses from 1630 ayahuasca drinkers (50.4% male, mean age = 43 years) to an open-ended question about their integration experiences after consuming ayahuasca. Inductive codebook thematic analysis was used to identify themes in participants' integration experiences. Participants described integration experiences in three main ways. First, was an overall appraisal of the integration experience (e.g., as easy, challenging, or long-term/ongoing). Second, was describing beneficial tools which facilitated integration (e.g., connecting with a like-minded community and ongoing practice of yoga, meditation, journaling, etc.). Third, was describing integration challenges (e.g., feeling disconnected, going back to "old life" with new understandings, etc.). These findings suggest that integrating ayahuasca experiences can be challenging and take considerable time, though working through integration challenges may facilitate positive growth. Findings also challenge the role of individual psychotherapy as the primary integration tool in Western psychedelic therapy, suggesting that communal and somatic elements may also be useful. An expanded definition of psychedelic integration is proposed which includes working with integration challenges and adjusting to life changes.