Chronic pain as an emergent property of a complex system and the potential roles of psychedelic therapies.

Despite research advances and urgent calls by national and global health organizations, clinical outcomes for millions of people suffering with chronic pain remain poor. We suggest bringing the lens of complexity science to this problem, conceptualizing chronic pain as an emergent property of a complex biopsychosocial system. We frame pain-related physiology, neuroscience, developmental psychology, learning, and epigenetics as components and mini-systems that interact together and with changing socioenvironmental conditions, as an overarching complex system that gives rise to the emergent phenomenon of chronic pain. We postulate that the behavior of complex systems may help to explain persistence of chronic pain despite current treatments. From this perspective, chronic pain may benefit from therapies that can be both disruptive and adaptive at higher orders within the complex system. We explore psychedelic-assisted therapies and how these may overlap with and complement mindfulness-based approaches to this end. Both mindfulness and psychedelic therapies have been shown to have transdiagnostic value, due in part to disruptive effects on rigid cognitive, emotional, and behavioral patterns as well their ability to promote neuroplasticity. Psychedelic therapies may hold unique promise for the management of chronic pain.

MDMA-assisted therapy is associated with a reduction in chronic pain among people with post-traumatic stress disorder.

Introduction: Increasing evidence demonstrates 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy (MDMA-AT) may be a safe and effective treatment for post-traumatic stress disorder (PTSD). There is growing interest in MDMA-AT to address a range of other health challenges. Chronic pain and PTSD are frequently comorbid, reciprocally interdependent conditions, though the possible role of MDMA-AT in treating chronic pain remains under-investigated. The present analysis examined the impact of manualized MDMA-AT on chronic pain severity among participants with PTSD who were enrolled in a Phase 2 clinical trial investigating MDMA-AT for PTSD (NCT03282123). Materials and methods: Exploratory data from a subset of participants who completed chronic pain measures (n = 32) were drawn from a Phase 2 open-label study sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS). Multivariable analysis of variance (ANOVA) was utilized to compare pre- vs. post-treatment Chronic Pain Grade Scale (CPGS) values, adjusting for demographics (age, sex, and ethnicity). K-means clustering was then used to group the sample into three clusters to denote high (n = 9), medium (n = 11), and low (n = 12) baseline pain severity, and the same analysis was repeated for each cluster. Results: Among the 32 participants included in this analysis, 59% (n = 19) were women, 72% (n = 23) were white, and median age was 38 years [interquartile range (IQR) = 31-47]. Overall, 84% (n = 27) reported having pain, and 75% (n = 24) reported disability associated with their pain. Significant reductions in CPGS subscales for pain intensity and disability score, and overall CPGS severity grade were observed among participants in the highest pain cluster (n = 9, p < 0.05), and for pain intensity in the medium pain cluster (n = 11, p < 0.05) post- vs. pre-treatment. Discussion: Findings demonstrate a high prevalence of chronic pain in this sample of people with severe PTSD and that chronic pain scores among medium and high pain subgroups were significantly lower following MDMA-AT. While these data are preliminary, when considered alongside the frequency of comorbid chronic pain and PTSD and promising efficacy of MDMA-AT for treating PTSD, these findings encourage further research exploring the role of MDMA-AT for chronic pain.

Safety considerations in the evolving legal landscape of psychedelic-assisted psychotherapy.

International drug policy is rapidly evolving in tandem with promising evidence for psychedelic-assisted psychotherapy (PAP) in treating a range of mental health conditions. Canada is among the countries increasingly expanding access to psychedelic substances for therapeutic purposes. The 8-year ban on medical exemptions through the Canadian Special Access Programme was recently reversed in January 2022 and the first exemptions for legal possession and personal use of psilocybin mushrooms were granted in 2020, nearly 50 years since their criminalization. In view of the evolving evidence base and regulatory landscape for PAP illustrated by recent shifts in Canadian and international drug policy, this piece seeks to clarify the special range of factors which ought to be considered to safely expand access to psychedelics. Streamlining access to safe and evidence-based compassionate use of PAP will provide a timely treatment option to those currently in need while encouraging further research and outcome surveillance to refine best practices.

Psychedelic use is associated with reduced daily opioid use among people who use illicit drugs in a Canadian setting.

BACKGROUND: Research into the therapeutic and naturalistic uses of psychedelics for improving outcomes related to mental health disorders has generated increasing interest in recent years. While controlled clinical trials of psychedelics have signaled benefits for treating substance use disorders, this area has not been well studied in the context of naturalistic psychedelic use. This study sought to investigate the possible relationship between recent naturalistic psychedelic use and subsequent daily illicit opioid use among people who use drugs (PWUD). METHODS: Data (2006-2018) were drawn from three harmonized prospective cohorts of community-recruited PWUD in Vancouver, Canada. We used multivariable generalized linear mixed-effects modeling (GLMM) to estimate the independent association between psychedelic use and subsequent daily illicit opioid use. RESULTS: Among 3813 PWUD at baseline, 1093 (29%) reported daily use of illicit opioids and 229 (6%) reported psychedelic use in the past six months. Over study follow-up after adjusting for a range of potential confounders, psychedelic use remained independently associated with a significantly reduced odds of subsequent daily opioid use (Adjusted Odds Ratio: 0.45; 95% Confidence Interval: 0.29 to 0.70). CONCLUSION: While confirmation in other settings is required, these findings align with growing evidence that psychedelic use may be associated with detectable reductions in subsequent substance use including illicit opioid use.