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TOPLINE:

A single dose of psilocybin combined with psychotherapy was linked to a greater likelihood of cocaine abstinence, a higher percent of cocaine-free days, and a reduced risk for cocaine lapse at 180 days compared with an active placebo plus psychotherapy in adults with cocaine use disorder (CUD), a new study showed.

METHODOLOGY:

• A randomized, quadruple-blind, placebo-controlled clinical trial was conducted in the US between 2015 and 2023 and included 40 adults with CUD (median age, 50 years; 82.5% men; 82.5% Black individuals) who were motivated to quit and had no notable comorbidities.
• Participants were randomly assigned to receive either a single oral dose of psilocybin at 25 mg per 70 kg of body weight (median dose, 32 mg) or an active placebo (100 mg of diphenhydramine) during an all-day investigational drug treatment session.
• They also received manualized psychotherapy that incorporated cognitive-behavioral treatment 1 month before the all-day drug treatment session and 1 month following the session.
• The primary outcomes were percentage of cocaine-abstinent days, complete cocaine abstinence rates, and time to first cocaine lapse through 180 days after end of treatment, which were assessed via interviews and confirmed using urinalysis. Adverse events (AEs) were also recorded during the study.

TAKEAWAY:

• Psilocybin recipients reported a higher overall percentage of cocaine-abstinent days than active placebo recipients (P < .001). They also had 26.3 more percentage points of abstinent days during the integration period, 35.9 more percentage points from the final integration session through day 90, and 28.4 more percentage points from day 90 through day 180 (P < .001 for all).
• Cocaine abstinence from the start of the integration period through day 180 was achieved by 30% of the psilocybin group vs none of the placebo group, with psilocybin recipients more likely to report abstinence during this period (odds ratio, 18.4; P = .007).
• Psilocybin was also associated with a significantly reduced risk for cocaine lapse over time compared with placebo (hazard ratio, 0.3; P = .001), with a 90-day survival probability of 55% vs 21% (P < .001).
• AEs occurred in 65% of psilocybin users vs 10% of placebo users, with no serious treatment-related AEs reported.

IN PRACTICE:

“This randomized clinical trial is the first, to our knowledge, to demonstrate that psilocybin coupled with psychotherapy may be safe and efficacious in the treatment of CUD,” the investigators wrote. However, they added that large trials are now needed to confirm the findings.

The author of an accompanying editorial cautioned that if the results “are framed prematurely as broadly efficacious, without emphasis on the full treatment regimen (ie, intensive psychotherapy) and safety protocols, there may be a rise in consumption and associated adverse events among a vulnerable population seeking relief.”

SOURCE:

The study was led by Peter S. Hendricks, PhD, The University of Alabama at Birmingham Heersink School of Medicine. The editorial was authored by Erin E. Bonar, PhD, University of Michigan, Ann Arbor, Michigan. Both articles were published online on May 07 in JAMA Network Open.

LIMITATIONS:

The study was limited by blinding-related challenges, with 90% of the psilocybin group guessing their allocation. The involvement of the lead author as primary therapist may have introduced allegiance bias, reliance on self-reported cocaine use could have affected outcome accuracy, and underreporting remained possible. Additional limitations included the small sample size of the study and a lack of generalizability to routine clinical populations.

DISCLOSURES:

The study was funded by The University of Alabama at Birmingham and the Heffter Research Institute. Disclosure information for study investigators is available in the original article. The editorialist reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.