Treating Cocaine Use Disorder: Is Psilocybin the Answer?

“This is definitely a milestone in the field of psychedelic research.”

Christopher Nicholas, PhD, clinical psychologist, University of Wisconsin

“Remember that just because you hit bottom doesn’t mean you have to stay there."

Robert Downey Jr., American actor and film producer

As an infectious disease specialist, I spent part of my career treating the downstream consequences of drug use - consequences that extend far beyond addiction itself into the realm of devastating but often preventable infection. Substance use disorders are among the most significant risk factors for infectious disease transmission, operating through two distinct but interconnected pathways: the direct inoculation of bloodborne pathogens through shared needles, and the erosion of judgment and self-protective behavior that accompanies intoxication. Robert F. Kennedy Jr.’s now-infamous admission - “I’m not scared of a germ. I used to snort cocaine off toilet seats.”- is more than a colorful anecdote; it is an unwitting clinical case study.

Over 40 million Americans have tried cocaine at least once in their lifetime and an estimated 1.5 million Americans meet the clinical criteria for cocaine use disorder. (Schwartz, EKC, et al., “Cocaine Use Disorder (CUD): Current Clinical Perspectives,” Substance Abuse Rehabilitation, September 3, 2022). Knowing of the extreme paucity of effective treatments for cocaine dependence (there are none), I was intrigued by a recent study reporting that psilocybin—a chemical found in certain kinds of mushrooms (“shrooms”) - might help treat cocaine use disorder. (Hendriks, PS, et al., “Psilocybin in the Treatment of Cocaine Use Disorder: A Randomized Clinical Trial,” JAMA Network Open, May 26, 2026). Hence, this week’s post.

The fungus among us (recap). A fungus is any member of the group of eukaryotic organisms—a group that includes yeasts and molds, as well as the more familiar mushrooms. There are an estimated 3.5-5.1 million fungal species on Earth but only 300 are human pathogens while about 2,000 species are considered edible. (Some people consider the morel mushroom to be “the most delicious of all fungi.”)

What is psilocybin? Psilocybin is a chemical in certain types of mushrooms. These psychedelic mushrooms or “shrooms” grow on nearly every continent and have a long history of use in traditional ceremonies. In 1958, the Swiss chemist Albert Hoffman isolated psilocybin from Psilocybe mushrooms and synthesized it.

Psilocybin is a “psychedelic” agent which means it belongs to a class of psychoactive substances that profoundly alter perception, mood, and cognitive processes. In the U.S., psychedelics are considered illegal under the Controlled Substances Act. (Native American ceremonial use of peyote is protected under federal regulation in at least 28 states.) Nonetheless, some people use shrooms recreationally or, allegedly, to improve their mental health.

Brief history of psilocybin addiction research. In the 1970s, psilocybin became a Schedule I controlled substance in the U.S. and research on this psychedelic agent essentially stopped. Then in the 1990s and 2000s, studies of psilocybin were revived when researchers at Johns Hopkins University, the University of New Mexico and other institutions showed that with nicotine and alcohol dependence, psilocybin could produce profound changes in mood, cognition, and personality-related behavior. By the summer of 2022, at least one landmark alcohol treatment trial had been published. (Bogenschutz, MP, et al., “Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs. Placebo in the Treatment of Adults with Alcohol Use Disorder,” JAMA Psychiatry, August 24, 2022). Currently, the National Institute of Drug Abuse, one of the 27 separate institute and centers within the National Institutes of Health, is overseeing over 60 ongoing psilocybin clinical trials. (A summary of what’s known about psilocybin can be found in the article “Diversity, biology, and history of psilocybin-containing fungi: Suggestions for research and technological development,”  in the April 2022 issue of Fungal Biology.)

Psilocybin as a treatment for Cocaine Use Disorder. Cocaine Use Disorder leads to roughly 22,000 deaths in the U.S. every year. The U.S. Food and Drug Administration (FDA) has approved no treatments for this disorder.

Recently, researchers at the University of Alabama Birmingham Heersink School of Medicine used psilocybin for the first time to treat cocaine use disorder. They found that a single dose of psilocybin combined with about 10 psychotherapy sessions could reduce cocaine use and lower relapse risk. (Hendriks, PS, et al., “Psilocybin in the Treatment of Cocaine Use Disorder: A Randomized Clinical Trial,” JAMA Network Open, May 26, 2026). Their findings suggest psilocybin shows promise as a novel treatment for cocaine use disorder.

The precise mechanism whereby psilocybin works isn’t fully established; it appears, however, to start with the neurotransmitter serotonin—especially 5-HT2A. Psilocybin is first converted to psilocin, which strongly stimulates the serotonin 5-HT2A receptor, particularly on cortical neurons, producing major changes in cortical signaling and glutamate transmission.

While the complexity of psilocybin’s effects has yet to be fully established, a major concept is that the psychedelic experience in some way creates a ‘window’ for more effective psychotherapy. A remarkable feature of this treatment paradigm is that the modern psychedelic approach is trying to achieve a durable behavioral change from only one or a few carefully supervised psychotherapy sessions rather than suppressing addiction by continuous daily medication. Hopefully, further randomized trials of psilocybin will support the findings of Dr.  Hendricks and colleagues at the University of Alabama.

A mushrooming field.  Studies of the use of psilocybin in the treatment of a variety of substance abuse disorders—alcohol, nicotine, and cocaine, as well as in treatment for post-traumatic stress disorder and treatment-resistant depression—suggest that taking this mushroom derivative is quite safe. Nonetheless, last year Johns Hopkins University opened the first of its kind “Clinic for Post-Psychedelic Difficulties.”

Characterizing psilocybin’s safety as well as its efficacy seem increasingly urgent. On April 18, 2026, President Trump issued an executive order “Accelerating Medical Treatments for Serious Mental Illness” directing federal agencies to fast-track research and streamline the FDA review process for psychedelic therapies like psylocibin. If these studies demonstrate safety and efficacy, the number of people on psilocybin will, in all likelihood, mushroom.