Can psilocybin treat both cocaine addiction and depression simultaneously?

A five-year, $3.4 million award has enabled a team of UTHealth Houston researchers to investigate the efficacy of psilocybin-assisted therapy for individuals suffering from both cocaine use disorder and major depressive disorder. The study aims to determine if this psychedelic compound can serve as a viable treatment option for these co-occurring conditions, which frequently present together in clinical settings.

Rationale for Combined Treatment Approach

Thomas D. Meyer, PhD, co-principal investigator and professor in the Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences at McGovern Medical School, highlighted the high comorbidity rate between the two disorders. "A lot of people with cocaine use disorder also have depression," Meyer stated. He noted that while evidence supports psilocybin’s effectiveness for depression, current treatments often address each condition separately. "Instead of treating each condition separately, why don't we target people with comorbid cocaine use disorder and depression?" he asked. Meyer also serves as director of the Psychological Intervention and Research Program on Mood Spectrum Disorders at UTHealth Houston.

The research will enroll approximately 50 adults diagnosed with both conditions in a 12-week trial conducted at a UTHealth Houston clinic. Participants will receive up to two doses of psilocybin, a naturally occurring psychedelic compound known for its hallucinogenic effects and commonly referred to as "magic mushrooms." Alongside drug administration, subjects will undergo multiple sessions of acceptance and commitment therapy (ACT), a form of talk therapy designed to enhance psychological flexibility.

Neuroplasticity and Cognitive Flexibility

Joy M. Schmitz, PhD, another co-principal investigator, explained the biological mechanisms potentially at play. Schmitz is a professor and director of the Center for Neurobehavioral Research on Addiction at McGovern Medical School, holding the Louis A. Faillace, MD, Chair in the Department of Psychiatry and Behavioral Sciences and the title of Louis A. Faillace, MD, Distinguished Professor. "Psilocybin has shown the ability to promote neuroplasticity in the brain," she said. She added that the compound appears to "enhance communication across brain regions and increase cognitive flexibility."

This increased flexibility may benefit patients who struggle with rigid patterns of thinking, feeling, and behaving associated with their disorders. Angela Stotts, PhD, co-principal investigator and professor in the Department of Family and Community Medicine at McGovern Medical School, described ACT as an empirically supported treatment targeting values-based behavior change. Stotts, who also serves as vice chair for research and director of the Behavioral Health and Addiction Research Program, expressed hope that combining psilocybin with ACT would help participants alter ingrained behaviors such as cocaine use.

Meyer emphasized the importance of therapeutic preparation and integration. "The preparation therapy before dosing is a critical part of the process because it helps participants get ready for the session," he said. He noted that subsequent integration sessions allow patients to interpret their experiences and translate insights into meaningful therapeutic change. The team anticipates that the combined approach will simultaneously reduce depressive symptoms and increase abstinence from cocaine. Brain scans taken throughout the study will be evaluated to observe physiological changes in response to the drug.

Epidemiological Context and Funding

Cocaine addiction, clinically termed cocaine use disorder, affects roughly 1.4 million people in the United States, according to the 2022 National Survey on Drug Use and Health. Within this population, lifetime prevalence estimates for depression reach as high as 40%. Individuals using cocaine experience depression at significantly higher rates than non-users. Unlike major depressive disorder, no FDA-approved interventions currently exist for cocaine addiction.

The study receives funding from the National Institute on Drug Abuse, a component of the National Institutes of Health. Additional UTHealth Houston researchers involved in the project include Jair C. Soares, MD, PhD; Michael Weaver, MD; Wen Li, PhD; Charles Green, PhD; and Dan Petrovitch, PhD. For further details regarding the trial, interested parties may contact the Center for Neurobehavioral Research on Addiction at 713-486-2800.