Neuropharmacology
April 2, 2023
Farah Z Zia, Michael H Baumann, Sean J Belouin et al.
28 citations
Chronic pain is a leading cause of disability and opioid overdose in the United States. While many people manage pain with existing medicines and psychosocial treatments, others find these options ineffective or unacceptable due to side effects and risks. Preliminary evidence suggests psychedelics may improve quality of life, functionality, and reduce disability and distress for people whose pain may never be completely relieved. This commentary calls for more basic research and clinical trials to explore psychedelics' potential in chronic pain management, and to determine whether effects stem from direct antinociceptive or anti-inflammatory mechanisms, or from increased tolerability, acceptance, and spirituality that mediate therapeutic effects seen in psychiatric disorders.
JAMA psychiatry
January 1, 2023
Brian D Kiluk, Bethea A Kleykamp, Sandra D Comer et al.
22 citations
A review sponsored by a public-private partnership addresses clinical trial design for new opioid use disorder (OUD) treatments that target systems other than the μ-opioid receptor. The authors present consensus recommendations for evaluating novel therapies such as cannabinoids, psychedelics, sedative-hypnotics, and immunotherapeutics. Key design elements include specifying the treatment stage (e.g., early abstinence, long-term recovery), defining the treatment's role (adjunctive or independent), selecting patient-informed primary outcomes that assess opioid use patterns, retention, and quality of life, and monitoring adverse events like relapse or overdose, especially when patients are not on maintenance opioid agonist or antagonist medications. Incorporating input from people with lived experience is urged to accelerate development and uptake of effective therapeutics.
The journal of pain
October 1, 2022
Robert H Dworkin, Brian T Anderson, Nick Andrews et al.
22 citations
Psychedelic substances have been used historically for spiritual and mystical experiences, and recent interest focuses on their potential to treat chronic pain. Clinical trials support psychedelics' effectiveness for psychiatric conditions, but studies on chronic pain—such as cancer pain, phantom limb pain, migraine, and cluster headache—are few and mostly uncontrolled. Risks are relatively rare with careful patient screening and supervision. Key challenges include identifying mechanisms of action, selecting appropriate pain conditions, designing rigorous trials with proper control groups, minimizing unblinding bias, and accounting for patient mindset and setting. Evidence-based recommendations are needed for future research to yield informative results.
Neuroscience and biobehavioral reviews
November 1, 2023
Sophia Linguiti, Jacob W Vogel, Valerie J Sydnor et al.
15 citations
A systematic review of 91 fMRI studies on acute psychedelic effects found substantial methodological heterogeneity. Only 51 unique samples were used across the 91 papers, and 54% of studies did not meet current standards for correcting Type I errors or controlling motion artifacts. Psilocybin and LSD consistently modulated connectivity along the sensorimotor-association cortical axis. Ketamine consistently increased activation in the dorsomedial prefrontal cortex. The review calls for future adoption of pre-registration, standardized processing and statistical testing, and data sharing to improve rigor.