Psilocybin Therapy for Obsessive-Compulsive Disorder (OCD)

MAY 27, 2024

Written by Aaron Nesmith-Beck & the Odyssey Team

Clinically Reviewed by Brian Pilecki, PhD

Evidence is growing for the use of psilocybin-assisted therapy in the treatment of Obsessive-Compulsive Disorder (OCD). In this article, we introduce OCD, review the published literature on psilocybin for OCD, discuss potential mechanisms of action, provide an overview of ongoing research, and highlight the experience of a former Odyssey client whose OCD symptoms vastly improved after their psilocybin session. We aim to provide a balanced overview of current evidence that can serve as a resource for individuals suffering from OCD, their loved ones, and their medical or mental health care providers.

OCD: A Severe Condition in Need of Novel Treatment Methods

OCD is a debilitating psychiatric condition characterized by intrusive thoughts called obsessions, repetitive behaviors called compulsions, and avoidance behaviors.1 OCD has an estimated lifetime prevalence of 2-3%, affecting millions directly and millions more with its downstream effects.2 It can be a particularly disabling condition, with a high disease burden that significantly impacts quality of life.3,4

Current first-line treatments for OCD include cognitive-behavioral and exposure-based therapy, and prescription medications such as selective serotonin reuptake inhibitors (SSRIs). While these approaches can be effective, 30-40% of patients do not respond at all to SSRI treatment, and there are waiting periods of weeks or months for symptom improvement in those that do.5 Relapse is also common after discontinuing or completing these treatments.6 The debilitating impact of OCD can be so severe that neurosurgery is used to treat intractable cases.7 There is often also a large treatment gap, with more individuals with OCD in need of care than those who actually receive treatment.8

Considering the severity of OCD, and the limited efficacy and accessibility of existing treatments, there is a significant need for novel treatment methods. Early research suggests that psilocybin, especially when administered in a therapeutic setting with professional support, may be an effective treatment for OCD, due to both its pharmacological properties and the characteristics of the subjective psychedelic experience it induces.

Published Research on Psilocybin for OCD

The published literature on psilocybin for OCD includes controlled studies, case studies, and survey studies. Each provides a different form of evidence for the potential efficacy of psilocybin as treatment for OCD.

Proof-of-concept study

A 2006 proof-of-concept study enrolled nine participants who met DSM-IV criteria for OCD. Participants each engaged in up to four psilocybin sessions, spaced at least one week apart. Participants were required to have had at least one prior failed treatment with a prescription medication for OCD (e.g. an SSRI), and at least one prior psychedelic experience.

Participants were screened for safety and administered psilocybin in a supervised setting. In line with the protocol used in most psychedelic clinical trials and research studies, during the session they were asked to wear eye shades and listen to a playlist of curated music. Overall, psilocybin was found to be physiologically safe and well-tolerated.

This study used four doses (very low, low, medium, and high) in escalating fashion with the very low dose randomized and intended as placebo. All nine participants received the very low dose, seven received the very low dose and medium dose, and six received all four doses.

During one or more sessions, significant decreases in OCD symptoms (23%–100% reduction in YBOCS score) were observed in all participants. Almost 90% of participants maintained a 25% decrease in YBOCS score and 67% maintained a 50% decrease in YBOCS score 24 hours after at least one of the sessions.

A limitation of this study is that systematic measurement was only completed for up to 24 hours post-session. However, two of the participants reported their improvement lasted most of the following week after the study, and one reported long-term remission of OCD symptoms at a six-month follow-up.

This study is significant as the first controlled experiment with psilocybin for OCD, with promising results. Notably, participants who received the very low dose of psilocybin (initially intended as a placebo and expected to have no effect) experienced higher than expected reductions in OCD symptoms. This study also found no clear relationship between dose and change in YBOCS score, and–in contrast to other research on psilocybin for mental health and addiction–no correlation between perceived intensity of psychedelic experience and reduction in YBOCS score.9

Case studies

Several case studies describe individuals with OCD who experienced improvements in their condition following the use of psilocybin.

A 2022 case study followed an individual who participated in an ongoing study at Yale University trialing psilocybin for OCD. The individual had longstanding treatment-resistant OCD, and received a single dose of psilocybin along with preparation and integration support. This case study is notable and instructive as the first systematic, long-term research on an individual with OCD who engaged in a psilocybin session in a therapeutic setting with professional support before, during, and after the session.

The study describes:

At 12 weeks post-dose, Daniel reported that OCD was no longer a significant part of his life, despite having a persistent “imprint” of obsessions and compulsions in his mind. He felt that if he didn't continue to work at managing this imprint, he could “slip back,” but even if that happened, he now had the “tools” to manage it. Referring to his OCD, he said, “Even if this were to come back, I'm on it.”

Improvements continued at 1.5 years post-session, although a particularly stressful life event briefly caused OCD symptoms to re-emerge. Using the psychological tools he’d learned from his experience, Daniel was able to successfully navigate the situation.

Daniel remarked that effectively addressing this symptom recurrence highlighted for him that he “still carried the toolkit” of insights and skills he learned from his experience in the psilocybin treatment study. He feels he can apply it at “any time” he needs. He described that the change he experienced through the study “wasn't only a singular transformation” but that the “toolkit” also “provided a sustainable means for ongoing transformation.10

This account aligns with our approach at Odyssey, which encourages viewing a psilocybin experience as part of an ongoing process, and not a “quick fix” or “silver bullet”. Ideally, a psilocybin experience takes place in the context of broader psychological and emotional work. This may include psychotherapy, which we recommend engaging in before and after a session, and may also include practices such as meditation or journaling, which have been shown in research to support personal work with psychedelics.11

Several other case studies report on individuals with OCD who consumed psilocybin-containing mushrooms outside of a controlled setting.

A 2021 case study describes an individual who self-administered psilocybin mushrooms multiple times over a several month period. He reported significant reductions in obsessive thoughts, compulsions, and other symptoms, and improved functioning, wellbeing, and quality of life. His YBOCS score decreased from 35 (three days before first psilocybin experience) to 13 (six months after first psilocybin experience).12

A 2014 case study describes an individual with severe, treatment-resistant OCD who had sought treatment from various forms of therapy and prescription medications without success. He consumed psilocybin mushrooms at home, with a friend present. The next day, his intrusive thoughts were significantly reduced. This individual continued to consume psilocybin mushrooms approximately every three weeks, and reported that this kept symptoms away. A year later, he reported that he had remained symptom-free.13

A 1997 case study describes an individual who had suffered from severe, incapacitating OCD symptoms since age 6. In his early twenties he began ingesting psilocybin mushrooms twice weekly, because he noticed substantial improvements in his OCD symptoms during the experiences. This individual consumed psilocybin daily for the next four years, having developed a tolerance to the subjective psychedelic effects but still noticing improvements in his OCD symptoms. He stopped taking psilocybin and was mostly symptom-free for two years, before the OCD symptoms gradually returned.14

A 1987 case study describes an individual who suffered from severe, debilitating OCD since age 13. This individual had used a range of substances including classic psychedelics (LSD, psilocybin, mescaline). He reported that LSD caused a temporary worsening of OCD symptoms, followed by relief for 4-5 hours. He reported that psilocybin and mescaline caused his obsessive thoughts to completely disappear.15

Survey study

A 2023 study surveyed 174 participants suffering from OCD symptoms about the impact of different psychoactive drugs on their condition. Only classic psychedelics, including psilocybin, were reported as effective at reducing OCD symptoms.

Respondents reported improvement in OCD symptoms lasting varying lengths of time: 33% reported less than a week, 21% reported between one week and one month, 12% reported between one and three months, and 33% reported more than three months. 10% of participants also reported worsening OCD symptoms.

The magnitude of therapeutic effect was associated with the intensity and pleasantness of psychedelic effects. Intensity of psychedelic effects was associated with dose, suggesting that moderate to high doses are more effective at generating therapeutic benefit.16

This study is notable for its large sample size and as the first survey investigating the relationship between psychedelics and OCD. However, survey studies rely purely on subjective reports and are not as reliable as other forms of data.

Mechanisms of Action: How Might Psilocybin for OCD work?

There are several potential explanations for the effects of psilocybin on OCD, at different levels of analysis.

Changes in brain chemistry

At the level of brain chemistry and neurotransmitters, psilocybin acts primarily on the serotonin system.17 Since the best-supported class of medication for OCD is serotonin reuptake inhibitors (SSRIs), which also act on this system, there may be overlapping therapeutic effects.

Research suggests that glutamate, an excitatory neurotransmitter and the most abundant neurotransmitter in the brain, may also contribute to OCD.18 A secondary effect of psilocybin’s impact on serotonin can be changes in glutamate, which could also have therapeutic benefit for OCD.19

Changes in brain network activity and connectivity

At the brain network or functional connectivity level, psilocybin has been shown to alter connectivity within and between brain regions. A particularly relevant area is the default mode network (DMN), which is highly involved in self-referential mental activity (e.g. thoughts about one’s personality, recalling past personal experiences, envisioning future personal events, etc.). The DMN has been shown to have increased connectivity and activity in individuals with OCD, so the effects of psilocybin in changing these patterns may result in therapeutic benefit.20 Changing patterns in the DMN also appears to connect to psilocybin’s effects on alleviating depression.21

Psychological and emotional effects of the psilocybin experience

At the psychological and emotional level, psilocybin’s subjective effects may have a role in the alleviation of OCD symptoms. In general, psilocybin helps process psychological and emotional material, and creates new perspectives, insights, and ways of relating to familiar internal and external phenomena. Psilocybin has been shown to increase cognitive and psychological flexibility, and increase openness to new experiences.22,23 It’s easy to see how these effects could be therapeutic towards a condition characterized by rigidity, repetition, and fixation.

Research on psilocybin for depression has shown that psilocybin can reduce doubt and rumination, which are strongly associated with the obsessions of OCD.24 Other psilocybin research has shown a shift from avoidance to acceptance of emotions, which is significant as OCD is associated with substantial emotional difficulties.25 During the course of working with psilocybin, new and helpful ways of relating to emotion may be uncovered naturally during a session and/or learned from facilitators during preparation and integration.

The mystical or spiritual aspects of the psilocybin experience may also contribute to therapeutic outcomes for individuals with OCD. This may include a sense of awe, acutely experienced bliss or boundlessness, the experience of contacting a reality that is “more real” or “more true” than ordinary reality, and an experience of direct connection with the divine. These experiences have been shown in research to result in decreased stress and anxiety, reductions in addictive behavior, improved overall wellbeing, and a range of other benefits.26

Discussion: A multi-mechanism effect?

Two participants in the open-label trial who received only a very low dose of psilocybin (initially intended as a placebo) and two individuals described in case studies (one who was taking prescription medications that blunt psilocybin’s effects, and the other who consumed psilocybin so frequently he developed a tolerance) experienced substantial therapeutic benefit from psilocybin, without experiencing a subjective psychedelic effect.8,10,12 This suggests some purely pharmacological impact of psilocybin at the level of brain chemistry and/or functional connectivity on improving OCD symptoms, particularly in the short term.

The detailed case report of the participant in the Yale study, as well as study protocols for all of the current research on psilocybin for OCD, suggest that experiencing psilocybin in a therapeutic setting with professional support for preparation, integration, and the session is more likely to create longer-term improvements in OCD.

Psilocybin Dosage and Session Frequency for OCD

Most current studies use a dose range of 25-30 mg of psilocybin as a therapeutic dose. This is in line with the dose range used in most other modern psychedelic clinical trials and research studies, and the dose range we use at Odyssey. A lower dose of approximately 10 mg or less is sometimes also used, either as placebo or to ensure safety preceding the therapeutic dose(s).

The majority of studies use two psilocybin sessions, spaced one to four weeks apart, with some using only one session, and some up to three. It’s important to note that the results from these ongoing studies have not yet been published, and the optimal psilocybin dose and session frequency for OCD has yet to be determined.

Ongoing Research Trials on Psilocybin for the Treatment of OCD

Here we provide a list of current ongoing studies on psilocybin for OCD, with a brief summary and link to the clinicaltrials.gov page with more information.

A double-blind, placebo-controlled trial at Yale School of Medicine aims to investigate the clinical and neural effects of psilocybin on OCD symptoms. The study protocol involves two psilocybin sessions, approximately one week apart, with preparation and integration sessions before and after.

More information is available on the Yale Medicine website and at clinicaltrials.gov: Efficacy of Psilocybin in OCD: a Double-Blind, Placebo-Controlled Study

Another study at Yale aims to investigate the effects of repeated psilocybin dosing on OCD, and compare the effects of one compared to two doses. A detailed overview of the study protocol has been published in Frontiers in Psychiatry.

More information is available here: Effects of Repeated Psilocybin Dosing in OCD

A study at Johns Hopkins is investigating the feasibility, safety, and efficacy of psilocybin for OCD in 30 participants, using two doses of psilocybin spaced approximately two weeks apart.

More information is available here: Effects of Psilocybin in Obsessive Compulsive Disorder

An Imperial College London study is investigating the effects of psilocybin on cognitive inflexibility and neural plasticity in people with OCD. This study involves two moderate doses of psilocybin, spaced four weeks apart, and measurement methods including cognitive tasks and EEG recordings.

More information is available here: PsilOCD: A Pharmacological-Challenge Feasibility Study

A study at the University of Arizona will evaluate whether psilocybin improves symptoms of OCD, whether it is safely tolerated, and the mechanisms by which it works. This study will compare low-dose psilocybin, high-dose psilocybin, and a placebo (lorazepam).

More information is available here: Psilocybin for Treatment of Obsessive Compulsive Disorder (PSILOCD)

A study at the Centre for Addiction and Mental Health in Toronto, Canada will investigate the effects of two doses of psilocybin, spaced two weeks apart and with preparation and integration support, on 10 participants with treatment-resistant OCD.

More information is available here: Feasibility, Clinical Effects, and Safety of Psilocybin-assisted Psychotherapy for Treatment-resistant OCD (PAP-OCD)

A study at Beersheva Mental Health Center in Israel will investigate psilocybin-assisted therapy for treatment of severe OCD. Multiple preparation and integration sessions are included along with three psilocybin sessions: one with a low safety dose, and two with a high therapeutic dose.

More information is available here: Evaluating the Feasibility, Safety and Efficacy of Psychotherapy Assisted Psilocybin for Treatment of Severe OCD

Connor: An Odyssey Psilocybin & OCD Success Story

Connor (client’s name changed to protect their privacy) is a former Odyssey client who was struggling with OCD, and experienced substantial benefit following his psilocybin session. Here’s Connor’s story, in his own words:

'‘I was diagnosed with OCD 21 years ago. Since then I have tried so many different treatments and therapies that I have lost count. Over the years my symptoms have ebbed and flowed between pretty light and very disruptive to my life. I have been in weekly therapy for the past 5+ years and on a heavy SSRI dose.

Recently the symptoms were flaring up, becoming nearly unbearable at times. This pushed me back to the internet looking for more help. I found Odyssey. To say that was anything short of life changing would simply not be true. I worked with Gabe to find a facilitator and participate in a ceremony.

I’m 5 weeks post-ceremony writing this. Not only can I tell a difference in my symptoms, but everyone around me can. Immediately following the ceremony, I took my first normal shower and haven’t looked back. Previously, my shower ritual would take up to an hour and often require help from my wife. The night of my ceremony I took a 2 min shower with no assistance. I also feel compelled to take fewer showers during the day. This has easily given me back an hour of every day.

I also used to wipe my groceries off before putting them away. This too, was very time consuming. 2 weeks post-ceremony I put them away without cleaning them. And again I haven’t looked back. This has also given me back a significant amount of time every week.

There is no doubt that the benefits will continue to evolve. The ceremony has allowed me to do much more work within my talk therapy which has also contributed to the improvement of my symptoms. Before the ceremony, I had kind of stalled in my work there. My first week back, my therapist couldn’t believe the difference.

I’m so thankful for Odyssey and the experience they helped facilitate for me. It has helped me be a better father, husband, sibling and friend. I encourage anyone who could benefit (and I think that’s nearly everyone) to explore the opportunity and see if it could offer them similar benefits. They might just be weeks away from the life they were meant to live.”

Connor’s experience is inspiring and hopeful, and points to the promise of psilocybin as a potential novel and effective treatment for OCD. The Odyssey experience is based on protocols used in psychedelic clinical trials and research studies, including studies on psilocybin for OCD. Facilitators on our team also specialize in working with anxiety disorders, including OCD.

While the evidence is promising, it’s important to note that research is still early, and that it’s not possible to guarantee any specific experience of outcome from a psilocybin session. Odyssey does not claim or attempt to treat any medical or mental health condition, and Odyssey services are not a substitute for medical or mental health treatment.

Conclusion

Psilocybin may be a novel and effective treatment for obsessive-compulsive disorder (OCD). OCD is a condition in need of new treatment options, as it is often severely debilitating and existing treatments are limited by their efficacy and availability.

A proof-of-concept study showed promising results administering psilocybin to nine participants with OCD. A number of case studies describe accounts of individuals who—either as part of a research trial or outside of a controlled setting—ingested psilocybin and experienced substantial improvements in their condition. A survey study of 174 participants found that classic psychedelics, including psilocybin, were the only class of psychoactive substance reported to improve OCD symptoms.

There are several potential mechanisms of action for the effects of psilocybin on OCD. Psilocybin has effects on the serotonin system and the neurotransmitter glutamate, which are connected to OCD. Psilocybin alters functional connectivity within and between brain regions, especially the default mode network (DMN), which is heavily implicated in self-referential mental activity. Psilocybin increases psychological flexibility, emotional acceptance, and openness to new experience. Finally, psilocybin can induce a spiritual or mystical-type experience that is associated with a range of beneficial therapeutic outcomes.

There are a number of ongoing research studies on psilocybin for OCD at Yale University, Johns Hopkins University, Imperial College London, and other institutions. All study protocols involve experiencing psilocybin in a therapeutic setting with professional support for preparation, the psilocybin session, and integration. The average dose range is between 25-30 mg of psilocybin, and most studies are using two psilocybin doses, spaced one to four weeks apart.

Connor is a former Odyssey client who had suffered from OCD for many years. His psilocybin experience was—in his own words—“life changing”. He, and others around him, noticed immediate and lasting improvements in his condition following the experience.

We’re grateful to have been able to support Connor, and hope to support many more like him. If you or someone you know is suffering from OCD and you’re interested in psilocybin, we invite you to get in touch using the “Start Journey” button at the top of the page. We’d love to connect with you and see if Odyssey’s services are a good fit.

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