A new review from neuroethicist Eddie Jacobs, and published in the Journal of Psychedelic Studies, is suggesting psilocybin may have great potential as a treatment for obsessive-compulsive disorder (OCD). Jacobs, from King’s College London and the University of Oxford, says it is surprising how little focus has been on the therapeutic potential of psilocybin in treating OCD, and he points to a number of new clinical trials that are finally exploring this promising treatment.
The ongoing psychedelic science renaissance has delivered a number of remarkable breakthroughs in recent years. From the incredible results seen in MDMA-assisted psychotherapy trials for PTSD, to the equally potent data coming from psilocybin psychotherapy for major depression, we will inevitably see psychedelic medicine finally become a legal therapy within the next few years.
Psilocybin, a natural psychedelic compound found in magic mushrooms, has been granted Breakthrough Status designation by the FDA on two occasions in recent years for treatment-resistant depression and major depressive disorder. The Breakthrough Therapy status is an indication early clinical evidence is strong and clinically meaningful. Alongside depression, psilocybin therapy is also seen to be effective in helping terminal cancer patients deal with end of life anxiety.
How can psilocybin help OCD?
OCD is the fourth most common mental illness, after depression, substance abuse and specific phobias. Affecting more than 2 percent of people at some point in their life, OCD can be profoundly distressing and disruptive.
Eddie Jacobs’ interest in psilocybin for OCD arose when he discovered how little research attention had been directed at this particular therapeutic outcome. He suggests that, although much excitement surrounds the results of psilocybin therapy for conditions such as depression and anxiety, the treatment should hypothetically also be effective for OCD.
“OCD seems to perfectly encapsulate the sorts of maladaptive processes that we know – from clinical and experimental trials, and anecdotal report – psychedelics can interrupt rigidly repeating patterns of thought and behavior that people want to escape, but struggle to,” says Jacobs in an email to New Atlas.
Jacobs’ new review article set out to fill a gap in our body of knowledge, effectively summarizing what we know about OCD and psilocybin therapy, while also offering an outline of what research has been done up till now.
“There are reports from back in the first age of psychedelic therapy that suggested OCD symptoms were amendable to this sort of treatment,” says Jacobs. “Frustratingly, a lot of the research from those days doesn’t match up to modern standards of rigor, so we’re probably best to consider them clues pointing in a direction, rather than firm evidence in and of themselves. The other evidence for psilocybin in OCD – case reports and (quite a lot!) of anecdotal reports, are the same.”
Alongside these anecdotal reports and case studies there are several strong mechanistic hypotheses to explain how psilocybin could be useful in treating OCD. One of those hypotheses, for example, relates to a large-scale interconnected collection of brain regions, known as the default mode network (DMN).
The DMN is essentially the state of our brain when we are at rest, not sleeping, but instead the “default” mode of brain connectivity when we are not performing active tasks. DMN activity is linked with self-reflection and daydreaming, and dysfunction in one’s DMN has been associated with depression and anxiety.
Psilocybin has been found to serve a little like a reset button for a dysfunctional DMN. Imaging studies have revealed a single dose of psilocybin can temporarily disintegrate resting state networks such as the DMN. And many researchers hypothesize this pharmacological action plays a part in the positive therapeutic outcomes seen in psilocybin therapy.
Jacobs suggests there is some evidence dysfunctional DMN activity plays a role in OCD by enhancing self-referential cognitive processing. And it is reasonable to hypothesize psilocybin could help “reset” this dysfunction in OCD patients.
“The disruption and reintegration ‘reset’ in DMN activity that is seen with psilocybin may, in OCD patients, allow the easing of an overly strong, top-down filtering bias, thereby re-establishing normal responsiveness towards the environment,” explains Jacobs in the published review.
The one modern clinical trial
To date there has only been one clinical investigation of psilocybin for OCD, conducted in the early days of the psychedelic science renaissance by Francisco Moreno and colleagues at the University of Arizona. The study, published in 2006, recruited nine OCD patients classified with moderate to severe symptoms.
Each patient was administered three doses of psilocybin, separated a week apart, with each dose escalating in potency. As well as establishing a safety profile for administering the psychedelic in this type of cohort, the study was primarily looking at whether the treatment offers short-term relief from severe OCD symptoms in the 24-hour period following a dose.
The results found all patients displayed some kind of symptomatic relief from their OCD symptoms in the 24-hour period following a treatment. The long-term effects were less impressive, but still relevant, with two subjects reporting relief for up to a week, and one patient remarkably showing sustained remission from OCD symptoms at a six-month follow-up.
“OCD is currently not very well treated; even when our current approaches work, there’s still significant residual symptoms,” says Jacobs, in reference to the Moreno study. “Considering that context, and considering the Moreno study wanted to confirm an effect over the course of 24 hours following treatment, having a patient in remission six months later is pretty impressive.”
Moreno and his University of Arizona team are currently running a more rigorous, placebo-controlled trial investigating the effects of psilocybin on OCD. The trial involves eight weekly psilocybin doses, accompanied by comprehensive neuroimaging, and a long follow-up to measure any sustained effects six months later.
The drug, the therapy, or both?
An interesting question raised by Moreno’s work is whether psilocybin treatments need to be embedded within a larger therapeutic program. Most of the advanced clinical trial work investigating psilocybin for depression and anxiety incorporates one or two active drug sessions into a longer program involving preparatory psychotherapy and follow-up integration therapy. All up, a clinical treatment for psychedelic-assisted psychotherapy can last up to three months.
The Moreno research notably divorces a psilocybin session from any broad psychotherapy program. This implies the sole pharmacological effect of a few psilocybin doses is enough to generate broadly beneficial outcomes. Jacobs suggests psilocybin most likely does confer some degree of intrinsic pharmacological effect, but the current research also affirms the benefits are indeed amplified when integrated into a larger psychotherapeutic program.
“My sense is that, in general, psilocybin therapy is enhanced by placing it within a wider psychotherapeutic program: it’s well established now that there is an ‘afterglow’ period following a psychedelic session, where there is an enhanced level of psychological and neurological flexibility,” Jacobs tells New Atlas. “I suspect that in most conditions, this period of malleability is a powerful opportunity to make positive changes, which therapy can help.”
However, Jacobs also notes this does not mean administering psilocybin outside of psychotherapeutic structures would be useless. He says the ideal methods for administering psychedelic therapies have yet to be determined, and there may be some conditions that benefit from shorter therapies.
“… a long program of therapy is expensive to administer, and there may be some conditions for which this is a nice extra, rather than a necessity,” says Jacobs. “Perhaps OCD is one of these – you see a good deal of reports of people successfully self-medicating their OCD by microdosing Psilocybe mushrooms. OCD doesn’t tend to respond to placebos as much as other conditions, so it seems plausible that the treatment effect is real, and comes about by physiological, rather than psychological, processes.”
Moreno’s current clinical trial is not the only one investigating psilocybin’s potential for OCD. A similar Yale University clinical trial is underway looking primarily at the short-term effects of a single psilocybin dose on acute OCD symptoms. A UK organization called Orchard is also currently raising funds to conduct a psilocybin/OCD trial in association with a psychedelic research team from Imperial College London.
Ultimately, while all the signs promisingly suggest psilocybin therapy could be an effective treatment for OCD, the research is not quite there yet. And despite the explosion of progress in psychedelic science over the past decade, there are still huge hurdles slowing research down. Legal restrictions inhibit easy access to the psychedelic compounds; political and social taboos still frustrate academic processes and study approvals; and the inability to easily profit from these old, off-patent compounds mean big pharmaceutical companies have no interest in paying for novel studies.
So, while we may be seeing some incredible and innovative studies demonstrating novel therapeutic uses for psychedelic drugs, there are still a number of research questions that need to be answered. Not the least of which is exactly how psychedelic therapy works, and what are the best techniques to optimize its outcomes.
“We’re still a long, long way from determining how psilocybin (therapy) works,” says Jacobs. “There are a lot of dials to adjust that we have good reason to believe influence treatment success: e.g., dosage, number of sessions and space between them, style of therapy during and around the sessions. Frustratingly, the obstacles put in the way of psychedelic research mean it’s going to be a long time while we tune these dials to get the best effect.”
The new review article was published in the Journal of Psychedelic Studies.