5.2. Psilocybin
Psilocybin has been minimally studied in those with OUD, even though it is one of the most commonly investigated psychedelics in contemporary trials for psychiatric disorders.91 Although there are limited preclinical investigations of psilocybin in animal models of opioid addiction, it has shown efficacy in the treatment of AUD14 and tobacco use disorder15 in modern trials. Other evidence has shown that in large samples of naturalistic use, the classic serotonergic psychedelics as a group have been shown to be associated with 27% reduced risk of past-year opioid dependence and 55% reduced risk of daily illicit opioid use.92,93 When this relationship is assessed individually, there is some suggestion that lifetime psilocybin use may be associated with a 30% reduced odds of a past-year OUD diagnosis.94
There are several planned or ongoing registered studies examining the safety and efficacy of psilocybin in those with either OUD or who receive LTOT for chronic pain. One registered study plans an eight-week double-blind, controlled intervention of hallucinogenic psilocybin (30mg) versus a blinding dose of psilocybin (1mg), following an inpatient buprenorphine-naloxone induction for OUD [NCT06005662].95 Primary outcomes include opioid abstinence (timeline follow-back [TLFB]96 and urine toxicology), treatment retention, and reduction in days using opioids (self-report and urine toxicology). Secondary measures include quality of life (World Health Organization Quality of Life-BREF [WHOQOL-BREF]), depression (Beck Depression Inventory II [BDII]), anxiety (State-Trait Anxiety Inventory [STAI]), and abstinence from other non-opioid substance use (TLFB).
A Phase 1 study investigating the safety of psilocybin in persons with OUD who were recently stabilized on buprenorphine-naloxone is also currently underway [NCT04161066].97 This study aims to address two important questions; how psilocybin may impact the effectiveness of medications for OUD (MOUD) and how concurrent MOUD may affect psilocybin therapy. Assessments include safety and adverse events as well as opioid craving (opioid craving scale [OCS]) and opioid use (TLFB).
A planned randomized double-blind placebo-controlled study of those with OUD engaged in methadone treatment who are concurrently using other illicit opioids seeks to investigate primary outcomes of changes in non-medical opioid use (by self-report and urine toxicology) as well as quality of life (WHOQOL-BREF) [NCT05242029].98This study has two planned dosing sessions (at 40mg) with further randomization of the treatment group at the second dosing session to investigate the impact of two doses. Importantly, secondary outcomes include assessment of chronic pain, as well as measures of non-opioid substance use, mood, and sleep, which may help to further our understanding of psilocybin’s utility as a treatment of co-occurring OUD and chronic pain.