Psilocybin shows promise for cocaine addiction in small trial

A single dose of psilocybin, the active compound in magic mushrooms, may help treat cocaine addiction, according to results from a new clinical trial.

The study, published this month in JAMA Network Open, found that 19 participants who received a single dose of psilocybin were more likely to abstain from cocaine than 17 participants who received a placebo of diphenhydramine, a common antihistamine. Both groups worked with a therapist to process their experiences.

Dr. Peter Hendricks, a behavioral health professor at the University of Alabama at Birmingham and lead author of the study, said finding a treatment for cocaine use disorder is especially urgent. There are currently no FDA-approved medications for addiction to cocaine or other stimulants like methamphetamine.

Overdoses involving stimulants are killing more Americans each year. According to the latest U.N. global drug report, cocaine deaths are rising worldwide as cocaine production reaches an all-time high.

More than a decade ago, Hendricks was exploring how psilocybin could help keep people out of jail. A large local dataset showed that cocaine use was the single strongest predictor of criminal justice involvement and recidivism, Hendricks said, particularly among low-income Black men, who made up the majority of the study’s participants.

While white Americans are more likely to report lifetime cocaine use than Black Americans, Black Americans are more likely to be arrested for cocaine-related crimes, Hendricks noted.

Experts say the mechanism that likely makes psilocybin effective for cocaine may also work for other addictive substances. Robin Carhart-Harris, a neuroscience researcher who has studied how psychedelics work in the brain, said psychedelics increase neuroplasticity and psychological plasticity, or the ability to change thinking and behavior.

Addictions inherently involve a resistance to change rigid, impulsive behaviors, Carhart-Harris said.

Gabrielle Agin-Liebes, a clinical psychologist at the Yale School of Medicine, said psilocybin is different from most addiction medications that target the same neurochemical systems as the substance itself.

Medications for opioid use disorder act on the same receptors as opioids, and nicotine patches replace nicotine in tobacco. Psilocybin, however, produces a profound altered state of consciousness, typically in a single session within a structured psychotherapy context, Agin-Liebes explained. It is not a maintenance medication that people must keep taking.

“It’s more like a catalyst within a therapeutic process,” Agin-Liebes added.

The idea is that a single dose, with therapist guidance, can facilitate shifts in perspective and self-compassion that help people change their behavior. Psilocybin may be especially effective for cocaine because withdrawal symptoms are more psychological and less physically painful than for substances such as opioids or alcohol, Agin-Liebes said. Common cocaine withdrawal symptoms include bad dreams, agitation, depression and cravings.

A critical commentary published alongside the study noted that results might not be generally applicable because the study excluded people with comorbid depression and anxiety. However, Carhart-Harris pointed out that psilocybin shows promise for both those conditions.

Like addictions, depression and anxiety are disorders where people get stuck in ruts, Carhart-Harris said. Psilocybin may help people out of those ruts. Agin-Liebes and Hendricks agree that the study’s success indicates psilocybin for cocaine use disorder is a promising treatment that should proceed to larger-scale clinical trials.

The study is notable as the first psychedelic clinical trial to include a majority of Black participants. While many spiritual rituals involving psychedelics originated in Indigenous societies in Latin America and Africa, U.S. psychedelic culture today is often associated with Silicon Valley and elite, white personalities like Michael Pollan.

Agin-Liebes pointed out that a recent systematic review found participants in U.S.-based psychedelic clinical trials tend to have higher socioeconomic status and are disproportionately white relative to the general population.

There are several layers to this, Agin-Liebes said. Social media ads, university listservs and word-of-mouth recruitment for clinical trials may be more likely to reach affluent, white populations. Hendricks noted that when recruiting for the trial, “we wanted to recruit people who were dependent on cocaine or had cocaine use disorder, and wanted to stop.”

Ads recruiting for psychedelic trials often explicitly mention psychedelics, which attracts people already interested in receiving psychedelic treatment. For this trial, however, researchers simply advertised that they were looking for people trying to quit cocaine. “The sample that was recruited is representative of the population of people with cocaine use disorder and want to stop in Birmingham, Alabama,” Hendricks said.

That the trial was not designed to attract psychedelic enthusiasts may also mean it was less susceptible to the “expectation effect,” which can raise suspicions around psychedelic trial results. People volunteer because they already believe in psychedelics, and they can usually guess if they received a placebo because psychedelics have distinct effects.