Breakthrough Findings from University of Alabama at Birmingham Researchers

A recent clinical trial conducted at the University of Alabama at Birmingham (UAB) has revealed promising results for treating cocaine use disorder using a single dose of psilocybin combined with psychotherapy. This randomized, placebo-controlled study marks a significant step forward in addressing a long-standing challenge in addiction medicine, where no approved pharmacological treatments have previously proven effective.

Psilocybin, the primary psychoactive compound found in certain species of mushrooms known as "magic mushrooms," was administered as a one-time oral dose to participants struggling with cocaine dependence. When paired with structured cognitive-behavioral therapy sessions, it led to markedly higher rates of abstinence and lower relapse risks compared to the placebo group. This development highlights the growing role of university-led research in psychedelic-assisted therapies.

The trial's publication in JAMA Network Open, a journal affiliated with the American Medical Association, underscores its credibility and potential impact on clinical practice. Researchers at UAB's Heersink School of Medicine, including lead investigator Peter Hendricks, Ph.D., emphasized the study's focus on underrepresented populations, such as low-income individuals and Black Americans disproportionately affected by cocaine use disorder.

Understanding Cocaine Use Disorder: Scope and Challenges

Cocaine use disorder (CUD) is a chronic condition characterized by compulsive cocaine use despite harmful consequences, as defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). It involves neuroadaptations in brain reward pathways, particularly the mesolimbic dopamine system, leading to intense cravings, tolerance, and withdrawal symptoms like fatigue, depression, and agitation.

Globally, an estimated 25 million people reported cocaine use in 2025, with production reaching record highs according to the World Drug Report. In the United States, past-year cocaine use affects about 1.5 to 2 million individuals aged 12 and older, and roughly 20-25% develop CUD. Overdose deaths involving cocaine have surged, contributing to nearly one in five drug-related fatalities. Vulnerable groups, including those with low socioeconomic status, face higher risks due to limited access to care.

Traditional treatments rely on behavioral therapies like cognitive-behavioral therapy (CBT) and contingency management, but relapse rates remain high—often over 70% within a year. Despite billions invested in pharmacotherapy development, no FDA-approved medications exist for CUD, creating a critical unmet need that university researchers are now targeting with innovative approaches.

The Science Behind Psilocybin's Potential in Addiction Recovery

Psilocybin is metabolized into psilocin, which primarily acts as an agonist at serotonin 5-HT2A receptors in the brain. This activation disrupts default mode network activity, promotes emotional processing, and induces profound mystical experiences that can reframe addictive behaviors. A key mechanism is enhanced neuroplasticity—the brain's ability to form new neural connections.

Preclinical studies show psilocybin increases dendritic spine density and synaptic protein expression, such as AMPA/NMDA receptor ratios, fostering rewiring in addiction-related circuits like the prefrontal cortex and nucleus accumbens. This plasticity may weaken entrenched craving pathways and strengthen inhibitory control, explaining sustained benefits from a single dose.

• Promotes synaptogenesis and spinogenesis for lasting circuit changes.
• Reduces amygdala hyperactivity, lowering fear and craving responses.
• Facilitates ego dissolution, enabling perspective shifts on substance use.

Prior university research at Johns Hopkins demonstrated similar effects for alcohol and tobacco use disorders, setting the stage for CUD applications.

Inside the UAB Clinical Trial: Design and Participant Insights

The quadruple-blind trial enrolled 40 adults (median age 50, 82.5% male, 82.5% Black, 65% earning ≤$20,000 annually) motivated to quit cocaine, with recent use verified by urinalysis. Participants underwent 4-5 preparation sessions, a 7-day abstinence period, an 8-10 hour dosing session, and multiple integration sessions over 180 days.

Psilocybin dose: 25 mg/70 kg body weight (median 32 mg). Placebo: 100 mg diphenhydramine. All received manualized psychotherapy blending motivational enhancement and CBT. Outcomes were assessed via timeline follow-back and urinalysis at multiple intervals.

This inclusive recruitment addressed historical biases in psychedelic trials, where participants were often highly educated and affluent.

Photo by Laura Rivera on Unsplash

Impressive Outcomes: Abstinence Rates and Relapse Prevention

Psilocybin participants showed 28.95% more cocaine-abstinent days post-treatment (95% CI 18.22-39.67, P<.001). In the integration period, abstinence was 26.31 percentage points higher (Hedges g=1.40); by days 90-180, 28.36 points higher (g=1.51).

Complete abstinence through 180 days: 30% (6/20) vs. 0% placebo (OR 18.37, P=.007; NNT=3.33). Relapse risk dropped 72% (HR 0.28, 95% CI 0.13-0.60, P=.001), with 55% cocaine-free at 90 days vs. 21%.

These results far exceed typical behavioral therapy benchmarks.

Safety and Tolerability in a Real-World Population

No serious adverse events occurred. Psilocybin group reported more transient issues: hypertension (30% vs. 10%), emotional distress (25%). All resolved without intervention. High retention (90%) vs. placebo dropouts highlights tolerability.

• Cardiovascular monitoring essential due to transient blood pressure spikes.
• Psychological preparation mitigates acute anxiety.
• Suitable for comorbid nicotine dependence, common in CUD.

For full study details, see the JAMA Network Open publication.

Academic Experts Weigh In on the UAB Discovery

Stephen Ross, NYU psychiatrist, called results "remarkable," surpassing any prior CUD medication. NIDA's Nora Volkow praised inclusivity, urging replication for stimulants. UAB's Hendricks noted: "Our trial addresses gaps for vulnerable populations."

More perspectives in Science magazine's coverage.

University Centers Driving Psychedelic Addiction Research

UAB's Department of Psychiatry collaborates with Johns Hopkins' Center for Psychedelic and Consciousness Research, led by pioneers like Matthew Johnson, who contributed here. Johns Hopkins has conducted over 700 psilocybin sessions, proving efficacy for smoking cessation (80% abstinence at 12 months).

NYU Langone's Center for Psychedelic Medicine explores alcohol use disorder. These hubs train future researchers, fostering careers in neuroscience and psychiatry. Explore UAB's work via their news release.

Photo by Joshua Hoehne on Unsplash

Limitations and Next Steps in Academic Research

Small sample (n=40), potential unblinding (90% guessed correctly), and single-site design limit generalizability. COVID delays spanned 8 years. Larger multisite phase 3 trials are needed, as Hendricks advocates.

Funding challenges persist, but federal interest grows, with NIDA supporting psychedelic trials.

Implications for Patients, Policy, and Higher Education

If replicated, single-dose psilocybin could transform CUD care, reducing societal costs exceeding $50 billion annually in the US. Universities like UAB position themselves as leaders, attracting grants and talent in psychedelic science.

For academics, opportunities abound in clinical trials, neuropharmacology, and ethics. This study exemplifies how higher education drives solutions to public health crises.