Psilocybin therapy shows strong potential for treating cocaine addiction

Two newly published studies suggest that psychedelic compounds may offer a novel approach to treating cocaine addiction. A clinical trial published in JAMA Network Open found that psilocybin combined with psychotherapy helped people stop using cocaine. A complementary animal study published in Addiction Biology indicates that while psychedelics can help unlearn drug-seeking behaviors, pairing them with the right environmental support might be needed to prevent long-term relapse.

Cocaine use disorder is a chronic condition in which a person compulsively seeks and uses cocaine despite negative consequences to their health, finances, and personal life. Medical treatments for the disorder have long been lacking. For example, a 2021 review evaluated available treatments for cocaine addiction, highlighting that few medical options successfully help people stop using the drug.

To address this gap, researchers have begun exploring classic psychedelics. Psilocybin is the main psychoactive compound found in certain types of mushrooms, known for altering perception, mood, and cognitive processes. Recent studies have tested its potential to treat various substance use disorders by combining the drug with professional psychological support.

The results from these trials have been encouraging. For instance, a 2022 clinical trial found that psilocybin combined with therapy substantially reduced heavy drinking in people with alcohol addiction. Similarly, a 2026 trial found that the treatment helped people quit smoking cigarettes at much higher rates than standard nicotine patches.

Building on this research progression, scientists wanted to test whether psilocybin could yield similar benefits for cocaine use disorder. At the same time, preclinical researchers, who conduct studies using animal or lab models before testing in humans, sought to understand exactly how psychedelics influence the biological and behavioral mechanisms of addiction in isolation, without the influence of human psychotherapy.

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The human clinical trial was led by Peter S. Hendricks at the University of Alabama at Birmingham. The team recruited 40 adults diagnosed with cocaine use disorder who wanted to quit using the drug. The participants were randomly assigned to receive either a single oral dose of psilocybin or an active placebo. An active placebo is a control substance that produces mild noticeable side effects so participants cannot easily guess they received a fake treatment. In this case, the placebo was a dose of diphenhydramine, a common antihistamine.

Both groups participated in a structured psychotherapy program that included cognitive-behavioral techniques, which are therapy methods that help people identify and change harmful thought patterns and behaviors. They attended preparation sessions before the drug administration day and integration sessions afterward to process their experiences. The researchers specifically recruited individuals from demographic groups that are often underrepresented in psychedelic research. In the final sample, 82.5 percent of participants were Black, and 65 percent reported an annual income of $20,000 or less.

The findings suggest that psilocybin paired with therapy provides a strong protective effect against cocaine use. Over the 180 days following the treatment session, participants in the psilocybin group reported substantially more days without using cocaine compared to the placebo group. During the final three months of the study, the psilocybin group had about 28 more abstinent days out of every 100 days than the control group.

Additionally, the treatment helped a portion of participants stop using the drug entirely. Over the 180-day follow-up, 30 percent of those who received psilocybin maintained complete abstinence from cocaine. By comparison, none of the participants in the placebo group achieved complete abstinence over that same period.

To understand the isolated pharmacological effects of these treatments, meaning how the drugs interact chemically with the body and brain, a related animal study was led by Isis Rita Anzel Koutrouli at the National Institute of Mental Health in the Czech Republic. The team investigated how psilocybin and a different psychedelic compound, ibogaine, alter the learning processes associated with addiction. Ibogaine is a psychoactive substance derived from an African shrub that has been historically noted for its potential anti-addictive properties, though it operates differently in the brain than psilocybin.

The researchers trained male Wistar rats, a specific and widely used laboratory strain of white albino rats, to self-administer cocaine by pressing a lever. After the rats developed a reliable cocaine habit, the researchers initiated an extinction phase. During this phase, pressing the lever no longer provided the drug. The goal of extinction training is for the subject to unlearn the association between the action and the reward.

On the first and fifth days of the extinction phase, the rats were given injections of either psilocybin, ibogaine, or a saline placebo. Both psychedelics accelerated the extinction process. Rats treated with ibogaine pressed the lever less frequently starting after the first dose. Those treated with psilocybin showed a similar reduction in drug-seeking behavior following the second dose. Both drugs seemed to stabilize the animals’ behavior, helping them abandon the futile lever-pressing habit more efficiently than the placebo group.

The effects, however, did not translate to total relapse prevention. Six days after the final psychedelic dose, the researchers tested the rats by reintroducing the lights and sounds that had previously been paired with cocaine delivery. This triggers cue-induced reinstatement, a model of relapse. When faced with these triggers, the rats treated with psychedelics resumed pressing the lever just as frequently as the rats given the placebo.

These animal results highlight a nuanced reality about psychedelic treatments. The pharmacological effects of compounds like psilocybin and ibogaine appear to enhance behavioral flexibility, making it easier to break old habits. Yet, without the continuous environmental support or active psychotherapy provided in the human trial, the drugs alone did not block the urge to relapse when familiar drug cues returned.

The success seen in the human trial is in line with research covered by PsyPost in 2025, which found that a single dose of psilocybin paired with psychotherapy substantially reduced heavy drinking days in individuals with alcohol use disorder. The results also align with a 2026 study covered by PsyPost, which found that psilocybin and counseling produced higher rates of verified abstinence in cigarette smokers compared to standard nicotine patches.

As with all research, there are a few things to keep in mind. The human clinical trial featured a relatively small number of participants, which means the exact size of the treatment effect could vary in larger populations. Additionally, it is difficult to keep participants unaware of which treatment they receive in psychedelic studies, as the perceptual effects of the drug are very obvious. In this trial, 90 percent of the participants in the psilocybin group correctly guessed their assignment, which introduces the possibility that their expectations influenced their outcomes.

For the animal study, the researchers only tested male rats to avoid behavioral variations related to reproductive cycles. Testing female animals in the future will be necessary to see if the extinction-enhancing effects apply universally. The animal model also strips away the psychological and social elements of human addiction treatment. The rats did not receive the equivalent of human psychotherapy, which might be exactly why the drugs failed to protect them from cue-induced relapse.

Future research will need to test these interventions in larger, more diverse human samples to confirm the benefits. Scientists also hope to refine animal models to better understand how therapeutic environments interact with the biological changes caused by psychedelics.

The study, “Psilocybin in the Treatment of Cocaine Use Disorder: A Randomized Clinical Trial,” was authored by Peter S. Hendricks, Sara N. Lappan, Richard C. Shelton, Adrienne C. Lahti, Karen L. Cropsey, Matthew W. Johnson, Melissa Bradley, Otto Simonsson, Lori L. Davis, Daniel H. Grossman, and Cynthia E. Ortiz.

The study, “Psilocybin and Ibogaine in Cocaine-Seeking: Extinction Enhancement Without Relapse Prevention,” was authored by Isis Rita Anzel Koutrouli, Vojtěch Brejtr, Marek Schwendt, Kacper Witek, Chrysostomos Charalambous, Kristýna Aleksič, Nina Miniariková, Eva Lhotková, Martin Toman, Marek Nikolič, Radek Jurok, Petra Cihlářová, Vladimír Mazoch, Pavel Ryšánek, Martin Kuchař, Klára Šíchová, and Tomáš Páleníček.