Repeated doses of psilocybin show promise for treating obsessive-compulsive disorder

A new clinical trial suggests that multiple doses of psilocybin, the active compound in “magic mushrooms,” could provide substantial relief for individuals suffering from obsessive-compulsive disorder. The findings indicate that repeated weekly treatments are safe and tend to significantly reduce the severity of obsessive thoughts and compulsive behaviors. This research, published in the https://doi.org/10.1177/02698811261424214” target=”_blank”>Journal of Psychopharmacology, provides evidence for a new potential treatment avenue for those who have not found success with standard therapies.

Obsessive-compulsive disorder is a debilitating psychiatric condition characterized by intrusive thoughts and repetitive behaviors. These symptoms consume a significant amount of time and can severely disrupt daily functioning. Current standard treatments typically include a combination of cognitive behavioral therapy and daily medications like serotonin reuptake inhibitors.

However, these traditional approaches often fall short for many patients. People frequently experience delayed or incomplete symptom relief, and they sometimes struggle to adhere to the treatments due to unwanted side effects. Because of these challenges, scientists have sought alternative therapeutic approaches that might offer faster or more robust relief.

Psilocybin has recently emerged as a promising candidate for treating various psychiatric conditions. When ingested, the body converts it into psilocin, a chemical that binds to serotonin receptors in the brain. Scientists have observed that the substance tends to increase cognitive flexibility, which helps reduce the rigid thought patterns characteristic of obsessive-compulsive disorder.

Brain imaging studies also suggest that psilocybin alters activity across specific neural networks associated with habitual responding and error monitoring. This specific circuitry often functions atypically in people with repetitive behavioral conditions. These observations provided a strong foundation for researchers to evaluate the safety and effectiveness of the compound in a controlled clinical setting.

Francisco A. Moreno, a professor of psychiatry at the University of Arizona, explained that clinical observations inspired this line of inquiry. “In the mid-1990s I met a patient with treatment-resistant OCD who reported having had lasting benefit from OCD while using psychedelics,” Moreno said. “We wrote a case report in 1997, and a theoretical paper on the possible mechanisms of action in 1998.”

Following those initial observations, the research team conducted early tests to see if the substance was safe to administer. “We pursued a pilot study of various doses of psilocybin to explore safety and signal of efficacy acutely for OCD and published this in 2006,” Moreno noted. “The work was on hold for many years until we restarted this kind of work a few years back.”

To investigate this modern application, the researchers recruited fifteen adult participants aged 18 to 65. All participants had a confirmed diagnosis of moderate to severe obsessive-compulsive disorder and had previously failed to respond to at least one standard treatment. Before the trial began, those taking psychiatric medications had to slowly discontinue their use to ensure safety during the psilocybin sessions.

The study was divided into two distinct four-week phases. During the first phase, participants were randomly assigned to one of three groups, each containing five people. One group received a weekly high dose of psilocybin, another received a low dose, and the third received an active placebo called lorazepam, which is a common calming medication.

This first phase was double-blind, meaning neither the participants nor the researchers knew which substance was being administered. During the second phase of the trial, the remaining fourteen participants all received a high dose of psilocybin once a week for four weeks. This phase was single-blind, meaning the participants did not know for sure what dose they were receiving.

Each treatment day involved a ten-hour clinic visit. Participants ingested a capsule, wore eyeshades, and listened to a standardized music playlist. Two trained facilitators remained in the room to provide support, ensure safety, and guide the participants as they returned to a typical state of awareness at the end of the session.

To track changes over time, researchers used the Yale-Brown Obsessive Compulsive Scale, a standard clinical interview used to measure the severity of a person’s symptoms. The scientists administered this interview before the study began, during each treatment day, and periodically throughout the following weeks. They also monitored the participants for adverse side effects, suicidal thoughts, and any signs of psychosis.

The researchers found that the repeated psilocybin doses were generally well-tolerated by the participants. No serious adverse events or psychotic symptoms occurred, and there were no significant changes in suicidal thoughts. Some participants experienced mild side effects, with nausea being the most common issue reported during the low-dose sessions.

In terms of symptom relief, the high doses of psilocybin significantly reduced obsessive-compulsive symptoms during the first four weeks of the trial. On the days following the treatment sessions, those in the high-dose group exhibited noticeably lower symptom scores than those in the placebo group. This therapeutic benefit continued to hold steady when measured a full week after the dosing sessions.

By the end of the full eight-week program, the overall outcomes were substantial. After participants had received at least four high doses of psilocybin, about 73 percent experienced at least a 35 percent reduction in their symptom severity scores. Additionally, 40 percent of the participants experienced a complete remission of their symptoms by the end of the eighth week.

The researchers also noticed a cumulative effect over the course of the study. A higher total number of psilocybin doses tended to predict a greater overall reduction in obsessive and compulsive symptoms. When the researchers followed up with the participants six months later, the symptom reductions had diminished slightly but remained substantial for a large portion of the individuals.

This enduring relief was a particularly notable outcome for the research team. “The fact that most people who benefited from psilocybin initially remained well at 6 months was nice to see,” Moreno said.

“Since many people with OCD are unable to benefit from current treatment options due to lack of efficacy, intolerance, access challenges, and sometimes the disease itself, having alternative options that may offer rapid and lasting benefit is highly desirable,” Moreno explained. “In this study, psilocybin shows promise as a safe and effective option when used in a clinically controlled setting.”

Despite these promising outcomes, the study has several limitations that provide context for the findings. The most notable limitation is the small sample size of just fifteen participants. This limited group size reduces the statistical power of the data and makes it difficult to generalize the findings to the broader population.

The strict screening process also limits how broadly the results can be applied. “The safety findings in this study are the result of a careful selection of candidates for treatment, and a thoughtful protocol for protection of participants,” Moreno cautioned.

The intensive nature of the trial, which required long clinic visits and weekly travel, also placed a high burden on the participants. This requirement might have unintentionally selected for highly motivated individuals with strong support systems, which could skew the results. Also, blinding in psychedelic trials is notoriously difficult, as the intense psychoactive effects of a high dose are hard to mistake for a calming placebo.

While the use of a low-dose group and an active placebo helped mitigate some of this blinding issue, it remains a persistent challenge in psychedelic research. Another potential issue involved the participants’ previous medication use. Exploratory data suggests that participants who recently discontinued a serotonin medication to join the study were less likely to respond to the psilocybin treatment.

“Further research is needed in larger-scale studies to demonstrate clinical utility,” Moreno noted. “We hope to replicate these findings in larger-scale studies, work on dose findings, and determine the number of dosing sessions required to achieve lasting benefit.”

The research team is already planning their next steps to better understand how the compound works. “We are conducting additional studies exploring mechanisms of action, functional imaging changes, relation to subjective experiences, etc.,” Moreno said.

The study, “A randomized clinical trial of repeated doses of psilocybin for the treatment of obsessive-compulsive disorder,” was authored by Francisco A. Moreno, Katja E. Allen, Christopher B. Wiegand, Rajan Dunne, James I. Prickett, Brian Bayze, and John J. B. Allen.