Can psychedelics treat OCD? What the science and lived experience tells us

Psilocybin shows promise for OCD, while ketamine tells a more complicated story, both in the science and lived experience.

Over the past decade, psychedelics have moved from the margins of psychiatry into some of the world’s leading academic centres, where they are being investigated for conditions ranging from treatment-resistant depression and post-traumatic stress disorder (PTSD) to addiction, anorexia nervosa and end-of-life anxiety. The results have generated real excitement, particularly for psilocybin, where several large studies have shown rapid and sometimes sustained benefits after only one or two administrations. Researchers soon began asking whether these treatments might also help in obsessive-compulsive disorder (OCD), one of psychiatry’s most disabling and treatment-resistant illnesses.

The need is clear. OCD affects approximately 3% of people during their lifetime and remains a leading cause of disability worldwide. Selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy (CBT) incorporating Exposure and Response Prevention (ERP) remain the mainstays, but many patients respond inadequately or stay significantly symptomatic despite the best available care. This highlights the urgent need that exists for treatments that work through entirely different biological and psychological mechanisms.

A small but increasingly sophisticated body of research has begun to explore whether psychedelics might fill that gap - and is no longer confined to isolated case reports. We now have placebo-controlled trials of psilocybin, randomised studies of ketamine, qualitative analyses of patients’ experiences, mechanistic reviews and the first repeated-dose psilocybin trial. Having spent several months reviewing this literature in detail – and having undergone a course of ketamine-assisted psychedelic psychotherapy myself – I have found my views shifting substantially. The most interesting question, I now think, is no longer simply whether psychedelics work in OCD, but how they work, why some patients benefit while others deteriorate, how dose influences outcome, and what role psychotherapy should play alongside them.

Yet most of these questions remain unanswered. Psychedelics in OCD are, if anything, a messy business. Anyone who has taken psychedelics will know that a psychedelic ‘trip’ can go all over the place. But with OCD, this seems even more the case as the OCD often tries to actively control the psychedelic experience. In practice, some people with OCD get better, some get worse, some improve then relapse, and some stay the same – though on average many do improve with the classic psychedelics, especially psilocybin.

This article is not an argument for or against psychedelic therapy, nor is it clinical advice; it is an attempt to set out where the science and lived experience currently stands.

The evidence for psilocybin is becoming increasingly encouraging

Of all the psychedelics being investigated for OCD, psilocybin has produced the most consistently encouraging evidence. The published studies remain few, but there is now a degree of convergence across independent groups – spanning proof-of-concept work, placebo-controlled trials, qualitative analyses and systematic reviews – that was largely absent five years ago. None alone is definitive, but collectively they suggest the field has moved well beyond speculation.

The first important clinical study, by Prof Moreno and colleagues in 2006, gave up to four doses of psilocybin to nine patients with treatment-resistant OCD in a supervised setting. Designed to assess safety rather than efficacy, it nonetheless produced rapid symptom reductions in several participants. It could not establish efficacy, but it made two points at least. Firstly, psilocybin could be given safely to carefully selected patients, and secondly, altering serotonergic signalling through the 5-HT2A receptor could change obsessive-compulsive symptoms within hours rather than the weeks conventional antidepressants require.¹ I met Prof Moreno in London a few years ago and was struck by both his scientific rigour and his commitment to finding new ways to help people with OCD. His pioneering work laid the foundations for much of the research that came afterwards.

Unfortunately, little clinical research followed for almost a decade and a half after his 2006 study even as psychedelic work expanded rapidly in depression. But more recently, several groups have produced a more coherent body of evidence. The PsilOCD study, funded by Orchard OCD, examined a single 10 mg dose of psilocybin with psychological support – well above a microdose, but for many participants short of the profound mystical or ego-dissolution states seen at higher doses. Even so, participants showed rapid, significant reductions in OCD symptoms, particularly compulsions, lasting on average a week before diminishing – evidence that clinically meaningful anti-obsessional effects can occur without a fully immersive psychedelic experience.²

At the other end of the dosing range, the recent Yale placebo-controlled trial has given perhaps one of the strongest efficacy signals yet. Using a substantially higher dose, investigators saw clinically meaningful improvements that persisted in many participants for up to twelve weeks after a single treatment, although one participant with pre-existing chronic suicidal ideation developed severe active suicidal ideation after dosing that then resolved after 72 hours. The study is small and needs replication, but the size and durability of the responses are among the most encouraging findings in the field (see pre-print).³ Prof Chris Pittenger presented this at the recent Orchard OCD International Conference that we organised in London last month.

More intriguing still is the recent repeated-dose study by Prof Moreno and colleagues, in which participants ultimately received repeated low and higher-dose treatment. Around three-quarters met response criteria and roughly 40% achieved remission, with substantial improvements maintained six months later. It is also small and requires replication, but it raises two possibilities – repeated dosing may produce larger, more durable benefits than single-dose treatment, and lower and higher doses may engage partly different mechanisms rather than simply being weaker and stronger versions of the same thing.⁴ Recent reviews reinforce this cautiously optimistic picture, concluding that psilocybin has generated a credible efficacy signal while stressing the need for larger trials, longer follow-up and a better grasp of mechanism.⁵

The evidence remains early and sample sizes modest, and replication in larger multicentre studies will be essential. But unlike a decade ago, there is a consistent signal that psilocybin can reduce OCD symptoms in at least a proportion of patients. The more interesting question is no longer whether it is biologically active in OCD, but why some improve while others do not, how dose shapes outcome, and how these effects interact with psychological processes.

Caption: advert for the PSILOCD study of a 10gm dose of psilocybin for OCD carried out by Imperial College and the University of Hertfordshire and funded by Orchard OCD.

Ketamine: a much more mixed story

Ketamine is often discussed alongside psilocybin, but for OCD the two probably should not be viewed the same way (although, as I experienced myself, ketamine does induce strong psychedelic states). Ketamine, as I explain later, works on a range of receptors and neurotransmitters. It transformed the treatment of refractory depression and drew interest through its rapid glutamatergic effects, with glutamate also long being implicated in the pathophysiology of OCD. Confusingly for OCD, ketamine produces a glutamatergic surge, while all the learnings from our collaboration with Prof Trevor Robbins at the University of Cambridge point to needing to do the opposite and reduce glutamate in parts of the brain linked to OCD. Where independent psilocybin studies are beginning to converge, ketamine studies continue to produce highly variable results, with benefit in some patients but significant psychological deterioration in others.

Nevertheless, the first signal was encouraging but modest. Prof Rodriguez and colleagues’ randomised, placebo-controlled crossover study at Stanford University showed that intravenous ketamine could rapidly reduce obsessive symptoms in some unmedicated patients, with benefits lasting about a week in responders.⁶ Its importance was as much conceptual as clinical, as it showed for the first time that ketamine could rapidly influence obsessive-compulsive symptoms, thereby opening an avenue beyond serotonergic mechanisms – though it was small, made use of highly selected patients, and left the crucial questions of who responds, and how well, unanswered.

Replication has been disappointing. In an open-label study, Bloch and colleagues found significant reductions in symptom scores but no clinically meaningful response in any of 10 treatment-resistant patients within the first three days. This was despite several with comorbid depression experiencing substantial antidepressant effects – a reminder that evidence from depression cannot simply be extrapolated to OCD.⁷ Sharma and colleagues, reviewing repeated infusions in serotonin reuptake inhibitor-resistant OCD, found average Y-BOCS (Yale-Brown Obsessive Compulsive Scale) scores improved but only one participant showed a dramatic response and two partial responses; most saw little meaningful improvement despite multiple infusions.⁸ Beaglehole and colleagues, reporting on intramuscular ketamine, found encouraging signals and acceptable short-term safety, but nevertheless two participants withdrew because they found the dissociative effects intolerable – this is important as these treatments are not psychologically benign simply because they are given in a clinic.⁹

The greatest cause for caution, however, comes from reports of delayed deterioration. Niciu and colleagues described two patients with OCD and previous major depression who developed delayed-onset dysphoria, worsening anxiety and suicidal ideation after ketamine.¹⁰ This shows that significant post-treatment deterioration is possible, and that the period after administration may be as clinically important as the acute experience itself. In OCD, ketamine may at least temporarily destabilise cognitive and emotional processes in ways some patients find hard to tolerate. In my informal conversations with several leading experts in the field of OCD treatment, they told me that, in their clinical experience, ketamine tended either not to do anything for OCD or make their patients worse. One expert hypothesised that OCD by its circuit-based nature is a very different beast to depression and hence does not respond anywhere near as well to ketamine. On the other hand, new data presented by Prof Rodriguez at the Orchard OCD International Scientific Conference last month showed a sustained reduction in the YBOCS that lasted several weeks from ketamine infusion.

All this disparity has led several groups to ask whether ketamine might work better as a facilitator of psychotherapy than as a standalone treatment. Rodriguez and colleagues later showed that exposure-based CBT might prolong ketamine’s short-lived effects, and Bottemanne and colleagues proposed that ketamine-induced plasticity could transiently enhance the learning that underlies ERP.¹¹^,¹² These ideas are attractive because they shift attention from the drug towards the interaction between pharmacological plasticity and psychological learning, but remain largely theoretical and untested in adequately powered trials.

Overall, the ketamine literature warrants caution. Yes, there is clear biological activity and real benefit for some, but that is set against striking heterogeneity, modest efficacy, limited durability, and reports of delayed dysphoria and suicidal ideation in others. To me, that translates as supporting cautious optimism about psilocybin, but considerably greater caution about ketamine.

Reading the literature changed how I interpreted my own experience

It was against this background that I reflected on my own ketamine-assisted psychotherapy. Having studied the glutamate hypothesis of OCD for years, I assumed ketamine would act as a fairly direct anti-obsessional treatment; but that was almost certainly too simplistic of a view to take. Unlike psilocybin, whose principal target is reasonably well understood through 5-HT2A agonism, ketamine is far more complex: an NMDA receptor antagonist with downstream glutamatergic and plasticity effects, but also actions on GABAergic, dopaminergic, inflammatory and, at some doses, opioid systems. Which of these underlies any effect in OCD is unknown, with even the glutamatergic account, as mentioned above, confusing and hypothetical.

My own experience reflected that uncertainty. Ketamine was much more psychedelic, and at times more traumatic, than I expected. Rather than my OCD becoming quieter, somehow it seemed to become more prominent. Instead of the intrusive thoughts disappearing, I watched my mind keep trying to analyse the experience and construct a sense of certainty. On two occasions, new obsessional themes even emerged during the session itself. At the time, I took this to mean that the treatment had gone wrong, but I am now much less sure.

Indeed, conversations with the ketamine-for-OCD group at Stanford, and subsequent reading – particularly of Inference-Based CBT, alongside ERP, Acceptance and Commitment Therapy and Internal Family Systems – led me to wonder whether the sessions had not reduced my OCD directly but exposed psychological processes those therapies could then address. By that, I mean the ketamine may have revealed the disorder vividly rather than treating it.

A similar thing had happened to me while taking magic mushrooms: more than 20 years ago, during a long period of OCD remission, I took magic mushrooms recreationally, and for a few hours an old OCD theme briefly re-emerged before vanishing as the drug wore off. The difference with ketamine was that the novel OCD loops that emerged during my ketamine therapy persisted for days or weeks rather than hours.

What did all this mean? Why did ketamine produce these new OCD themes that then lasted days/weeks while the magic mushrooms triggered a temporary OCD relapse that lasted a few hours? Weren’t these drugs meant to alleviate OCD symptoms, rather than make them worse? These personal observations are not evidence and cannot establish mechanisms, but they mirrored the themes that emerge independently from the qualitative research I mention below – altered relationships with uncertainty, attempts to control the experience, and shifts in how those of us with OCD relate to our intrusive thoughts.

All this also brought home to me that these drugs need to be used cautiously and carefully – they are not miracle drugs that will immediately get rid of your OCD. For a few people, that might be the case, but for many of us, it will be a challenging and difficult journey to recovery using psychedelics. So if you are a person with OCD considering psilocybin or ketamine treatment for OCD, please be cautious and consider finding a clinician with expertise in both OCD and psychedelics to advise and assist you on your journey.

The qualitative studies may prove as useful as the clinical trial endpoints

The clinical endpoints from randomised trials tell us surprisingly little about the real effect of these psychedelic therapies on participants in those studies. That’s why I’m always keen to delve deeper when I see the scores of, say, the MADRS (Montgomery-Asberg Depression Rating Scale, used extensively in depression studies) or the Y-BOCS (Yale-Brown Obsessive Compulsive Scale, used extensively in OCD studies) or other clinical measures used in a psychedelic study. For a classic anti-depressant or anti-obsessive drug, those scales are fine, but for psychedelics, where the lived experience of the drug is so much more complex and messy, these measures – by their very nature – can only really give a rudimentary overview of what is happening – especially at higher doses with the full blown psychedelic experience. After all, these measures show whether headline symptoms improve and for how long (which, of course, is key for obtaining regulatory approval), but not so much what patients experience psychologically.

This is why the recent qualitative work from the Yale group matters (in their paper ‘Acute and post-dosing effects of single-dose psilocybin for obsessive-compulsive disorder: an interpretative phenomenological analysis’³). Following their placebo-controlled psilocybin trial, Ching and colleagues interviewed participants in detail about their experiences during and after treatment.¹³

The most striking observation was that psilocybin did not simply make OCD disappear. Many participants described a fundamentally altered relationship with their symptoms. Their intrusive thoughts often remained but carried less authority, and people felt less compelled to respond to them, more willing to tolerate uncertainty, and less driven to control their internal experience. These are not unfamiliar ideas, either – they resemble much of what exposure response prevention (ERP), Acceptance and Commitment Therapy (ACT) and, to some extent, Inference-Based CBT try to cultivate by very different routes. Because rather than eliminating obsessions, those therapies change how patients relate to them, and the Yale interviews suggest psilocybin may facilitate similar shifts.

Equally important is what the study says about patients who did not benefit straightforwardly. A recurring theme was that the OCD itself interfered with the psychedelic experience, with participants becoming caught in compulsive analysis, trying to control the altered state, dealing with arising obsessions, or becoming preoccupied with the question as to whether it was “working”. The authors describe several of these as “partial psychedelic experiences”, raising the possibility that obsessive-compulsive processes may themselves limit full engagement with the psychedelic state.¹³

OCD, in other words, may not simply be the target of treatment but an active participant in it. This challenges an assumption carried over from depression, where the experience is often thought to unfold naturally given good preparation and support. OCD, a disorder which by its very nature attempts to achieve certainty and maintain control, may activate those very processes during the psychedelic experience, thereby creating tension between surrendering to the experience and the disorder’s urge to monitor it. This may explain why old and new OCD themes emerged during my own ketamine and magic mushroom experiences and why I struggled so much with them. Indeed, if you go into Reddit forums where people with OCD discuss their experiences with psychedelics and ketamine, you will come across similar accounts. If so, OCD may require a rather different psychedelic treatment model from that used in depression.

Importantly, the Yale participants received supportive psychological care rather than intensive ERP, and many still improved substantially.¹³ Meaningful benefit can therefore occur without embedding treatment in extensive OCD-specific psychotherapy – though it raises natural questions. Namely, might some patients gain more from structured ERP, ACT or Inference-Based CBT afterwards? Are those whose OCD most interferes with the psychedelic state the ones who need more specialist psychological input in order to benefit? Could the full-blown psychedelic experience be a gateway for turbo-charging psychological therapy because of the insights it provides? The literature cannot yet say, although my personal experience tends to go in that direction as my ketamine sessions – even the challenging ones - did give rich insights that I then brought into my traditional therapy sessions later on.

So the questions are becoming more sophisticated, as it is no longer simply whether psychedelics improve OCD, but which psychological processes change, and why some respond far better than others. These are exactly the challenges that qualitative research is well placed to address. Indeed, carrying out more in-depth qualitative studies on the lived experience of OCD patients in psychedelic and/or ketamine studies would be absolutely fascinating not just for understanding the psychedelic experience but for understanding OCD too.

Is a full psychedelic experience really necessary?

One of the most interesting open questions is whether a profound psychedelic experience is actually necessary for benefit in OCD. Popular discussion has focused on mystical experiences and ego dissolution, which occur at higher doses and have been linked to good outcomes in depression. Whether they matter equally in OCD is far from clear.

The PsilOCD study is central here (although I must declare a bias here as this was a study funded through Orchard OCD, the charity that I co-founded). Its milder 10 mg dose still produced significant reductions in symptoms, particularly compulsions, a week after treatment,² which breaks the assumption that intense experiences are a necessary requirement for effective treatment. A lower-dose approach may also be more acceptable to apprehensive patients, easier to deliver in routine services, and less likely to produce overwhelming experiences – making implementation and tolerability significantly more straightforward.

The higher-dose Yale and Moreno studies offer a complementary rather than contradictory perspective, reporting encouraging and at times longer-lasting improvements.^3,4 But they differ too much in design to be compared directly. The more useful question is not whether low or high doses are “better” but whether they work through the same or different mechanisms. A 10 mg dose may produce sufficient neurobiological and psychological change to reduce obsessive-compulsive symptoms in many patients without requiring an intense psychedelic experience. Higher doses may engage additional psychological processes, perhaps through more profound alterations in emotional processing, self-referential thinking or cognitive flexibility. At present, the evidence does not allow us to distinguish between these possibilities.

Future dose-ranging studies should therefore aim not just to find an optimal dose but to understand what different doses actually do – comparing subjective experience, psychological flexibility, quality of life, durability and functional recovery alongside the Y-BOCS.

Psychedelic therapy for OCD may ultimately prove to be not a single intervention at different strengths, but a family of related interventions whose mechanisms and best applications differ by dose and by patient.

Where does the field go from here?

Only a few years ago the question was whether psychedelics had any role in OCD at all. I remember back in 2017 when we were first setting up Orchard OCD and started discussing the idea of psilocybin for OCD with Prof David Nutt, some other people I spoke to gave me curious looks. Fast forward to today and it is obvious that the field has moved well beyond that. The evidence is still preliminary and the studies small, but there is now a coherent body of work suggesting psilocybin can produce clinically meaningful improvement in at least a proportion of patients, while the ketamine literature has proved far more heterogeneous and inconclusive – a reminder that altered states of consciousness are not a single therapeutic category, and that different compounds may differ fundamentally in mechanism, efficacy and safety.

The biggest change, though, has been conceptual: the earliest studies asked simply whether symptoms improved, whereas the literature increasingly asks how these treatments change patients’ relationships with their obsessions, why some benefit while others deteriorate, and whether dose alters not just the magnitude of the response but its underlying mechanism.

If one idea has stayed with me, it is that psychedelic therapy in OCD may be less about eliminating obsessions than about temporarily changing the cognitive and emotional landscape in which they operate – whether through serotonergic, glutamatergic or other effects, altered network connectivity, increased neuroplasticity or some interaction of all of them. I remain optimistic but cautious, because psychedelic therapy for OCD should be neither romanticised nor dismissed. The psilocybin evidence is genuinely encouraging but early, and the ketamine evidence is more mixed, reminding us these interventions can cause distress as well as benefit. Our responsibility is to become neither evangelists nor sceptics, but to ask better questions, design better trials, and understand much more clearly which patients benefit, from which compounds, at which doses, and within which therapeutic frameworks.

If the last decade has taught us that psychedelics may have a place in OCD treatment, I hope the next will tell us how to use them safely, effectively and with the rigour that patients deserve.

(Written by Nick Sireau with assistance from Hannah Ellis, Communications Manager at Serenatis Bio, and with help from ChatGPT and Claude.)

References

1. Moreno FA, Wiegand CB, Taitano EK, Delgado PL. Safety, tolerability and efficacy of psilocybin in nine patients with obsessive-compulsive disorder. J Clin Psychiatry. 2006.

2. Pellegrini L, Fineberg NA, et al. PsilOCD: A phase 1 pharmacological challenge study of 10 mg psilocybin in obsessive-compulsive disorder. Eur Neuropsychopharmacol. 2025.

3. Kelmendi B, Pittenger C, Ching THW, et al. Randomised placebo-controlled trial of psilocybin for treatment-resistant obsessive-compulsive disorder. SSRN preprint. 2026.

4. Moreno FA, Allen KE, Wiegand CB, et al. A randomised clinical trial of repeated doses of psilocybin for the treatment of obsessive-compulsive disorder. J Psychopharmacol. 2026.

5. Collins A, et al. Psychedelics for obsessive-compulsive disorder: current evidence and future directions. Int J Neuropsychopharmacol. 2024.

6. Rodriguez CI, et al. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder. Neuropsychopharmacology. 2013.

7. Bloch MH, et al. Effects of ketamine in treatment-refractory obsessive-compulsive disorder. Biol Psychiatry. 2012.

8. Sharma LP, et al. Repeated intravenous ketamine in serotonin reuptake inhibitor-resistant obsessive-compulsive disorder. Asian J Psychiatr. 2020.

9. Beaglehole B, et al. Intramuscular ketamine for obsessive-compulsive disorder: a double-blind crossover study. Aust N Z J Psychiatry. 2024.

10. Niciu MJ, Grunschel BD, Corlett PR, Pittenger C, Bloch MH. Two cases of delayed-onset suicidal ideation, dysphoria and anxiety after ketamine infusion in patients with obsessive-compulsive disorder and a history of major depressive disorder. J Clin Psychiatry. 2013.

11. Rodriguez CI, et al. Can exposure-based CBT extend the effects of intravenous ketamine in obsessive-compulsive disorder? J Clin Psychiatry. 2016.

12. Bottemanne H, et al. Ketamine augmentation of exposure and response prevention for obsessive-compulsive disorder. Neurosci Biobehav Rev. 2022.

13. Ching THW, Kelmendi B, Pittenger C, et al. Acute and post-dosing effects of single-dose psilocybin for obsessive-compulsive disorder: an interpretative phenomenological analysis. Front Psychiatry. 2025.