Medicine or Recreation? Exploring Psychedelics, Cannabis, and Opioids in Modern Pain Management

Christian S. Guay, MD

The evolving landscape of pain management now encompasses substances once relegated to recreational use or stigmatized as dangerous. In the thought-provoking session, “Opioids, Cannabis and Psychedelics: Important Therapeutics or Just Getting High?” on Saturday, March 22, at the 2025 Annual Meeting, presented by IARS and SOCCA, three experts examined the evidence behind these controversial agents, balancing therapeutic potential against misuse concerns while challenging assumptions about their roles in modern medicine.

Karim Ladha, MD, a clinician-scientist and staff anesthesiologist at St. Michael’s Hospital and the University of Toronto, opened the session with an exploration of psychedelics for pain management. Dr. Ladha defined psychedelics as substances that change perception, mood, and cognition, with classical psychedelics functioning as serotonin-2A receptor agonists, including DMT, psilocybin, LSD, and mescaline. While these compounds have played prominent roles in religious and spiritual ceremonies across cultures for centuries, modern usage traces back to the synthesis of LSD in 1938.

Dr. Ladha outlined his team’s ongoing clinical trial investigating psilocybin for pain management. “Plausible mechanisms include 5-HT2A activation leading to neuroplasticity and suppression of inflammation, changes in brain functional connectivity, and mood improvement,” he explained. With only one previous small randomized controlled trial (10 patients) in the literature, Dr. Ladha’s study targets 30 patients with moderate-to-severe neuropathic pain who have not responded to at least two medication trials and have no previous psychedelic experience.

The intervention combines 25mg oral psilocybin (pure extract manufactured in Canada) with acceptance and commitment therapy, following three phases: preparation, a 4- to 6-hour dosing session, and integration sessions in subsequent weeks. The control group receives 400 mg dextromethorphan plus psychotherapy. While the primary outcome focuses on feasibility, secondary measures include pain questionnaires, mystical experience evaluation, mood, anxiety, quality of life, blinding adequacy, and adverse events. Dr. Ladha also highlighted nitrous oxide as another anesthetic agent with promising applications for depression and chronic pain.

Mark C. Bicket, MD, PhD, FASA, Co-Director of the Opioid Prescribing Engagement Network, Director of Pain and Opioid Research and Assistant Professor of Anesthesiology and Health Management and Policy at the University of Michigan, addressed the implications of cannabis use in perioperative and chronic pain management. “Evidence suggests cannabis can reduce some types of chronic pain, though adverse effects may include dizziness and nausea,” Dr. Bicket noted. He differentiated between cannabis products (edibles, tinctures, flower), cannabis-derived products, and synthetic cannabinoids, explaining that 38 states now have medical cannabis programs and 24 permit recreational use.

Chronic pain represents the most common qualifying condition for medical cannabis, followed by anxiety and posttraumatic stress disorder. While earlier studies suggested state cannabis laws decreased opioid prescribing and mortality, Dr. Bicket cautioned that more recent, methodologically robust research shows no meaningful differences between medical cannabis states and controls. Nevertheless, patient surveys indicate that approximately half of cannabis users report decreased pain medication use, and patients generally perceive cannabis as safer than prescription opioids (50% vs. 21% respectively).

Dr. Bicket highlighted potential perioperative concerns, noting that cannabis use may increase cardiovascular risk (coronary heart disease, stroke, new-onset arrhythmia) and possibly affect postoperative nausea and vomiting, pain, and opioid requirements — though not to a clinically meaningful extent. He recommended clinicians assess cannabis type, time of last consumption, administration route, amount, and frequency of use before surgery, suggesting delaying elective cases if consumption occurred within two hours.

Kristin L. Schreiber, MD, PhD, Associate Professor at Harvard Medical School and Vice Chair of Faculty Development in the Department of Anesthesiology, Perioperative and Pain Medicine at Brigham and Women’s Hospital, concluded the session by examining the transition from acute to chronic pain. “Most people have normal resolution of acute pain and don’t go on to develop chronic pain and chronic opioid use,” Dr. Schreiber explained, describing this progression as a continuum rather than a binary outcome. She presented data from observational cohort studies examining preoperative pain phenotypic assessment and identified substantial overlap between predictors of postoperative pain and postoperative opioid use.

A multicenter observational study found that while 14% of people were taking opioids at three months postsurgery (down from 20% preoperatively), only 3.3% represented new prolonged opioid users. Predictors of persistent postoperative opioid use included prior substance use or misuse, mental health disorders, younger age, and catastrophizing tendencies.

Dr. Schreiber emphasized that enhanced recovery after surgery (ERAS) protocols should focus on reducing pain rather than eliminating opioids. A large retrospective study found that greater intraoperative opioid administration was associated with fewer instances of uncontrolled pain, fewer new chronic pain diagnoses, fewer opioid prescriptions, and decreased persistent opioid use. “We don’t want to swing too far towards reducing opioids to the point of causing harm,” she cautioned, suggesting intraoperative methadone as an excellent alternative to traditional opioids for ERAS protocols.

This thought-provoking session challenged simplistic narratives about controversial therapeutic agents, highlighting the nuanced evidence behind psychedelics, cannabis, and opioids while acknowledging the ongoing need for balanced approaches to pain management that prioritize patient outcomes over ideological positions.