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.