Single moderate dose of psilocybin linked to temporary reduction in OCD symptoms

A new study suggests that a moderate dose of psilocybin can effectively reduce symptoms of obsessive-compulsive disorder for a short period. The findings indicate that the improvement is most pronounced in compulsive behaviors rather than obsessive thoughts. These results were published in the journal Comprehensive Psychiatry.

Obsessive-compulsive disorder, commonly known as OCD, is a chronic mental health condition. It is characterized by uncontrollable, recurring thoughts and repetitive behaviors. People with the disorder often feel the urge to repeat these behaviors to alleviate anxiety.

Standard treatments for the condition usually involve selective serotonin reuptake inhibitors or cognitive behavioral therapy. These treatments are not effective for everyone. A significant portion of patients do not find relief through traditional means. This has led scientists to explore alternative therapeutic options.

Psilocybin is the active psychoactive compound found in “magic mushrooms.” It has gained attention in recent years as a potential treatment for various psychiatric conditions. These conditions include depression, anxiety, and addiction.

Most research into psilocybin has focused on high doses that induce a profound psychedelic experience. However, there are concerns about using high doses for patients with OCD. Individuals with this disorder often struggle with a fear of losing control. The intense psychological effects of a high dose could theoretically be distressing for them.

Luca Pellegrini and his colleagues designed a study to test a different approach. Pellegrini is a researcher associated with the University of Hertfordshire and Imperial College London. The research team wanted to see if a moderate dose of psilocybin could offer therapeutic benefits without a potentially overwhelming psychedelic experience.

The researchers also aimed to determine if the biological effects of the drug could reduce symptoms independently of a “mystical” experience. This is a departure from many depression studies, which often link the therapeutic outcome to the intensity of the psychedelic journey.

The study involved 19 adult participants. All participants had a primary diagnosis of obsessive-compulsive disorder. The severity of their condition ranged from moderate to severe. They had been living with the disorder for at least one year.

The researchers employed a fixed-order, within-subject design. This means that every participant received the same treatments in the same order. There was no randomization of the dosage sequence.

Participants attended two dosing sessions separated by at least four weeks. In the first session, they received a very low dose of 1 mg of psilocybin. This served as a control or active placebo. It was expected to have minimal physiological or psychological effects.

In the second session, participants received a moderate dose of 10 mg of psilocybin. This dose was chosen to be high enough to potentially have a biological effect but low enough to minimize the risk of a challenging psychological experience.

The researchers engaged in extensive preparation with the participants. They provided psychological support before, during, and after the dosing sessions. However, this support was non-interventional. The therapists did not provide specific cognitive behavioral therapy or exposure therapy during the sessions.

During the dosing days, participants stayed in a calm and comfortable room. They were encouraged to lie down and listen to music. Therapists were present to ensure their safety and provide reassurance if needed.

The primary measure of success was the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). This is a standardized clinical tool used to rate the severity of OCD symptoms. The scale measures both obsessions and compulsions separately.

The researchers assessed the participants at several time points. These included the day before dosing, the day of dosing, and then one week, two weeks, and four weeks after each dose.

The results showed a clear difference between the two doses. The 10 mg dose led to a significant reduction in OCD symptoms one week after administration. The magnitude of this improvement was considered large in statistical terms.

In contrast, the 1 mg dose resulted in much smaller changes. The difference between the effects of the 10 mg dose and the 1 mg dose was statistically significant at the one-week mark.

The researchers observed that the beneficial effects began to fade after the first week. By the two-week mark, the difference between the two doses was no longer statistically significant. By four weeks, symptom levels had largely returned to baseline.

A specific finding regarding the nature of the symptom relief stands out. The data revealed that the reduction in total scores was driven primarily by a decrease in compulsions. The scores for obsessions did show some improvement, but the change was not statistically significant.

This suggests that psilocybin might have a specific effect on the mechanisms that drive repetitive behaviors. It appears to make it easier for patients to resist the urge to perform rituals. It seems less effective at stopping the intrusive thoughts themselves.

The study also measured symptoms of depression using the Montgomery-Åsberg Depression Rating Scale. Many patients with OCD also suffer from depression. However, the researchers found no significant change in depression scores following the 10 mg dose.

This lack of effect on depression contrasts with other studies on psilocybin. Those studies typically use higher doses, such as 25 mg. The participants in this study generally had low levels of depression to begin with. This may explain why no significant improvement was observed.

The safety profile of the 10 mg dose was favorable. Participants tolerated the drug well. There were few adverse events reported.

No serious adverse events occurred during the study. Some participants experienced mild anxiety or headaches. One participant experienced a brief anxiety attack after the 1 mg dose, but it was resolved quickly.

The absence of distressing perceptual abnormalities was a key outcome. The 10 mg dose did not induce hallucinations or the intense “trip” associated with higher doses. This supports the idea that a moderate dose is a feasible option for patients who might be afraid of losing control.

The study builds on a growing body of evidence regarding psychedelics and OCD. Previous research has hinted at the potential of these compounds.

A seminal study conducted by Moreno and colleagues in 2006 investigated psilocybin in nine patients. That study found that symptoms decreased markedly after psilocybin administration. It tested various doses and found that even lower doses offered some relief. The current study by Pellegrini and team validates those earlier findings with a larger sample and a focused 10 mg dose.

Other lines of research also support the idea that the psychedelic experience itself may not be necessary for symptom relief in OCD. A preclinical study on mice published in Translational Psychiatry explored this concept.

In that animal study, researchers used a “marble burying” test. This is a common behavior in mice used to model obsessive-compulsive traits. Mice treated with psilocybin buried significantly fewer marbles.

The researchers in the mouse study then administered a drug called buspirone alongside the psilocybin. Buspirone blocks the specific serotonin receptors responsible for the hallucinogenic effects. The mice still showed a reduction in marble burying. This suggests that the anti-compulsive effects of psilocybin might work through a different biological pathway than the psychedelic effects.

Case reports have also appeared in medical literature documenting similar effects. A report in the Journal of Psychoactive Drugs detailed the case of a 30-year-old man with severe, treatment-resistant OCD.

This patient consumed psilocybin mushrooms on his own. He reported that his symptoms completely disappeared during the experience. He also noted a lasting reduction in symptom severity for months afterward. His scores on the Y-BOCS dropped from the “extreme” range to the “mild” range.

Survey data provides additional context. A study published in Scientific Reports surveyed 174 people who had used psychedelics. Over 30% of participants with OCD symptoms reported positive effects lasting more than three months.

These participants reported reduced anxiety and a decreased need to engage in rituals. This retrospective data supports the clinical findings that psilocybin targets the behavioral aspects of the disorder.

Despite the promising results, the current study by Pellegrini has several limitations. The sample size was small, with only 19 participants. This limits the statistical power of the analysis.

The study did not use a randomized design. All participants received the 1 mg dose first and the 10 mg dose second. This was done to prevent any potential long-term effects of the higher dose from influencing the results of the lower dose.

However, this fixed order introduces potential bias. Participants may have expected the second dose to be more effective. The researchers attempted to blind the participants to the dose, but most participants correctly guessed when they received the higher dose.

The duration of the effect was relatively short. The significant improvement lasted only one week. This suggests that a single dose may not be a long-term cure.

The short duration implies that repeated dosing might be necessary to maintain the benefits. Future research will need to investigate the safety and efficacy of administering psilocybin on a recurring basis.

The distinction between obsessions and compulsions also requires further study. The finding that compulsions improved more than obsessions is largely preliminary. Larger studies are needed to confirm if this is a consistent pattern.

The researchers suggest that combining psilocybin with psychotherapy could enhance the results. While this study used non-interventional support, active therapy might help patients integrate the experience. Therapies like Exposure and Response Prevention could be more effective during the window of reduced symptoms.

Future clinical trials should use larger samples and randomized designs. They should also explore the potential of multiple doses. Comparing the 10 mg dose directly against the standard 25 mg dose would also be valuable.

The study, “Single-dose (10 mg) psilocybin reduces symptoms in adults with obsessive-compulsive disorder: A pharmacological challenge study,” was authored by Luca Pellegrini, Naomi A. Fineberg, Sorcha O’Connor, Ana Maria Frota Lisboa Pereira De Souza, Kate Godfrey, Sara Reed, Joseph Peill, Mairead Healy, Cyrus Rohani-Shukla, Hakjun Lee, Robin Carhart-Harris, Trevor W. Robbins, David Nutt, and David Erritzoe.