Emerging Data Suggest Psilocybin May Benefit Patients With Cocaine Use Disorder

Findings from a clinical trial (NCT02037126) published in JAMA Network indicate that psilocybin-assisted psychotherapy may offer a promising treatment strategy for cocaine use disorder (CUD), a condition that currently has no FDA-approved pharmacotherapies. The data revealed that participants who received psilocybin alongside manualized psychotherapy achieved significantly higher rates of cocaine abstinence and reduced risk of relapse compared with those who received placebo plus psychotherapy.¹

This trial, conducted at the University of Alabama at Birmingham, highlights growing interest in psychedelic-assisted therapies for substance use disorders, and the data may represent a meaningful advancement for patients who currently have limited treatment options.¹

Psilocybin and Its Role in Addiction Treatment

Psilocybin is a naturally occurring psychedelic agent found in specific mushroom species. Upon consumption, psilocybin is metabolized to psilocin, which acts as a 5-HT2A receptor agonist.² Prior data indicate this activity may enhance neuroplasticity, emotional processing, and cognitive flexibility, serving as a potential aid in helping patients cease maladaptive behavioral patterns associated with addiction.³

Although under federal law, psilocybin is classified as a Schedule I substance, its potential therapeutic benefits in conditions such as major depressive disorder, alcohol use disorder, tobacco dependence, and posttraumatic stress disorder have gained more traction in recent research.^4-6 Analyses of previous data revealed that psilocybin in alcohol and nicotine dependency led to improved abstinence outcomes in comparison with traditional approaches.^5,6 However, evidence in stimulant use disorders, specifically CUD, has been lacking.

CUD is an ongoing global public health concern. Research findings show that approximately 25 million individuals worldwide used cocaine in 2023 and that cocaine overdose-related deaths substantially increased in the United States in 2019.¹ Standard treatment approaches for CUD generally rely on behavioral interventions, such as contingency management, because pharmacologic therapies have consistently failed to demonstrate sufficient efficacy in clinical trials.⁷

Study Design

The randomized, quadruple-blind, placebo-controlled trial enrolled 40 adults with CUD who were motivated to quit cocaine use. The participants were randomly assigned 1:1 to receive either a singular oral dose of psilocybin at 25 mg per 70 kg body weight or an active placebo of 100 mg diphenhydramine.¹

All participants were required to undergo a structured psychotherapy program integrating cognitive behavioral therapy principles and supportive psychotherapy before and after the dosing session. The treatment protocol included approximately 1 month of preparatory psychotherapy followed by integration sessions after dosing.¹

The study population was notable for including historically underrepresented groups in psychedelic research. Most participants were Black men with low socioeconomic status and decades-long histories of cocaine use. The trial researchers emphasized that clinical trials evaluating psychedelics have historically enrolled participants with a higher socioeconomic status, highlighting the importance of this study from an equity and representation perspective.¹

The primary outcomes included percentage of cocaine-abstinent days, complete cocaine abstinence through 180 days, and time to first cocaine lapse. Abstinence was assessed through self-report and confirmed with urinalysis.¹

Key Findings

The findings showed significant improvements among participants receiving psilocybin-assisted therapy compared with placebo-assisted therapy. The psilocybin recipients displayed a critically greater percentage of cocaine-abstinent days across follow-up periods with an estimated treatment effect of approximately 29 additional abstinent percentage points.¹

Complete cocaine abstinence through 180 days was found in 30% of participants receiving psilocybin, while in the placebo group, no participants achieved complete abstinence. Furthermore, psilocybin recipients experienced a substantially lower risk of relapse over time, with an HR of 0.28 for cocaine lapse compared with placebo.¹

Notably, no adverse effects (AEs) associated with psilocybin administration were reported. Most AEs occurred during the dosing session and resolved without intervention.¹

Although these outcomes may be encouraging, the data indicate several limitations. The trial included a relatively small sample size, CIs were wide for some outcomes, and blinding proved difficult due to psilocybin’s noticeable psychoactive effects.¹

Psilocybin is not currently FDA approved for CUD, but these findings contribute to a growing body of literature suggesting psychedelic-assisted psychotherapy may become an important future area of addiction treatment research. Larger studies will ultimately determine whether psilocybin can transition from experimental therapy into broader clinical practice.

REFERENCES

1. Hendricks PS, Lappan SN, Shelton RC, et al. Psilocybin in the treatment of cocaine use disorder: a randomized clinical trial. JAMA Netw Open. 2026;9(5):e2611029. doi:10.1001/jamanetworkopen.2026.11029

2. Psilocybin for mental health and addiction: what you need to know. National Center for Complementary and Integrative Health. Updated May 2024. Accessed May 8, 2026. https://www.nccih.nih.gov/health/psilocybin-for-mental-health-and-addiction-what-you-need-to-know

3. Carhart-Harris RL, Goodwin GM. The therapeutic potential of psychedelic drugs: past, present, and future. Neuropsychopharmacology. 2017;42(11):2105-2113. doi:10.1038/npp.2017.84

4. Davis AK, Barrett FS, May DG, et al. Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2021;78(5):481-489. doi:10.1001/jamapsychiatry.2020.3285

5. Bogenschutz MP, Ross S, Bhatt Set, al. Percentage of heavy drinking days following psilocybin-assisted psychotherapy vs placebo in alcohol use disorder. JAMA Psychiatry. 2022;79(10):953-962. doi:10.1001/jamapsychiatry.2022.2096

6. Johnson MW, Garcia-Romeu A, Griffiths RR. Long-term follow-up of psilocybin-facilitated smoking cessation. Am J Drug Alcohol Abuse. 2017;43(1):55-60. doi:10.3109/00952990.2016.1170135

7. De Crescenzo F, Ciabattini M, D'Alò GL, et al. Comparative efficacy and acceptability of psychosocial interventions for individuals with cocaine and amphetamine addiction: a systematic review and network meta-analysis. PLoS Med. 2018;15(12):e1002715. doi:10.1371/journal.pmed.1002715