This observational case study of identical twins found that repeated low doses of psilocybin in one twin with severe obsessive-compulsive disorder (OCD) were linked to lower perceived symptom severity and better emotional well-being. However, the affected twin still showed impaired cognitive flexibility compared with the unaffected twin.
Background
Obsessive-Compulsive Disorder (OCD) can present significant challenges to individuals mental health, characterized by intrusive thoughts and repetitive maladaptive behaviors. Recent research into alternative treatments has highlighted psychedelics, notably psilocybin, for their potential therapeutic benefits in various psychiatric disorders, including OCD. This case study evaluated the impact of self-administered, low-doses of psilocybin, commonly referred to as microdosing, on symptom reduction and cognitive flexibility in OCD, with a focus on identical twins discordant for the condition.
Case presentation
The study documents the experiences of one twin diagnosed with OCD who began a regimen of low-doses of psilocybin containing mushrooms, while the other twin, unaffected by OCD, served as a comparison. Case X was diagnosed with OCD by a general practitioner in the Danish healthcare system. Following years of severe OCD, case X began a self-medicated regimen consisting of psilocybin containing mushrooms, corresponding to 1–5 mg of psilocybin, every 3rd day. The other twin, case Y, who remained unaffected by OCD, and did not take psilocybin containing mushrooms. Cognitive flexibility was evaluated in both cases using a set-shift task. The affected twin reported a notable reduction in OCD symptoms, along with improvements in emotional regulation and overall well-being. However, despite these symptomatic improvements, deficits in cognitive flexibility remained present compared to the unaffected twin.
Conclusion
This case study underscores the potential of low-doses of psilocybin as a promising avenue for mitigating symptoms of OCD. Nevertheless, the observed disparity in cognitive flexibility highlights the nuanced nature of OCD pathology, suggesting that while low-doses of psilocybin may alleviate certain symptoms, it may not fully address underlying cognitive impairments. Further research employing larger sample sizes and rigorous longitudinal designs is imperative to elucidate the mechanisms underlying the therapeutic effects of psilocybin low-doses in OCD, offering insights into its broader applicability as a treatment modality.
Papers cited by this study that are also in Blossom
Doss, M. K., Považan, M., Rosenberg, M. D. et al. · Translational Psychiatry (2021)
Hutten, N. P. W., Mason, N. L., Dolder, P. C. et al. · International Journal of Neuropsychopharmacology (2019)
Lea, T., Jungaberle, H., Schecke, H. et al. · Psychopharmacology (2020)
Hutten, N. P. W., Mason, N. L., Dolder, P. C. et al. · Frontiers in Psychiatry (2019)
Obsessive-compulsive disorder (OCD) is described as a highly disabling condition marked by intrusive obsessions and repetitive compulsions, with substantial effects on daily functioning, sleep, academic performance, social life, and family burden. The authors note that first-line treatments such as SSRIs and behavioural therapy do not lead to remission for a substantial proportion of patients, and SSRIs may also have delayed onset and adverse effects. They also emphasise that impaired cognitive flexibility may be an underlying feature of OCD, but this remains incompletely understood and may represent a relevant treatment target. In this context, psilocybin has attracted interest because earlier research has suggested possible benefits for OCD symptoms and for cognitive flexibility, although the evidence has been mixed. Drange and colleagues set out to examine whether repeated low doses of psilocybin, used in a self-medicated manner, were associated with reduced OCD symptoms and improved cognitive flexibility in a case of severe OCD. They specifically report an observational case study of identical twins, one affected by OCD and one unaffected, using a qualitative interview and a set-shift task to compare symptom experience and cognitive performance. The paper is presented as preliminary work in an area where there is no clear evidence yet on whether low-dose psilocybin affects cognitive flexibility in OCD.
This was an observational single-case study involving identical twin brothers. Case X was a 40-year-old man with severe OCD and comorbid attention deficit disorder, and case Y was his unaffected twin. The OCD diagnosis in case X was reported as having been made in the Danish healthcare system and was also confirmed by the study team using ICD-10 guidelines. Case X had tried several prior treatments, including SSRIs, methylphenidate for ADD, and self-taught acceptance and commitment therapy and mindfulness; case Y did not have OCD and did not use psilocybin. The exposure of interest was self-administered low-dose psilocybin. Case X initially used approximately 1 gram of hallucinogenic truffles from the grey market and later switched to homegrown psilocybin mushrooms in capsules of about 0.1 g each. The authors analysed a mushroom sample by LC-MS and reported that the home-grown material contained 3.9 mg psilocybin and 5.3 mg psilocin per capsule. The paper states that case X used psilocybin on a one-day-on, two-days-off schedule; the exact duration and total cumulative dose were not clearly quantified. To assess cognitive flexibility, the researchers administered the three-dimensional Inter-Extra Dimensional set-shift task, a computerised neuropsychological test adapted from the Wisconsin Card Sorting Test. This task assesses the ability to shift responses according to changing rules and feedback across seven stages, with stage 7 being the most demanding. The extracted text also states that the twins took part in a qualitative interview. The paper does not clearly describe any formal statistical analysis beyond comparing task performance between the twins and relating it to the interview material.
Case X reported a marked subjective reduction in OCD symptom severity after starting low-dose psilocybin, alongside improved emotional regulation, quality of life, and a feeling of being more able to accept distress rather than react compulsively. According to his account, symptom improvement became noticeable to others after around 6 months, and after 2 years he described himself as nearly free of OCD. During the interview, his Obsessive Compulsive Inventory-Revised score was reported as less than 21, whereas scores above 40 were described in the paper as generally indicating OCD. Case X reported no adverse effects from psilocybin, although he described stigma and anxiety related to obtaining the substance illegally. The cognitive testing did not show restoration of cognitive flexibility in the OCD-affected twin. On the Inter-Extra Dimensional set-shift task, case X attempted more trials than case Y in stage 7 (48 versus 19) and made more errors (25 versus 8). The authors interpret this as poorer performance on the most difficult extradimensional shift component, consistent with impaired cognitive flexibility in case X compared with his unaffected twin. The paper therefore reports a dissociation between subjective symptom improvement and objective task performance. The qualitative interview suggested that case X and case Y both viewed the brother's improvement as likely reflecting a combination of psilocybin with psychotherapy, mindfulness, and other factors rather than psilocybin alone. In the quoted material, case X described psilocybin as making acceptance easier and reducing discomfort, and he characterised the change as substantial in terms of perceived well-being. The paper presents these accounts as supportive of symptom relief, but not as evidence of a causal treatment effect.
Drange and colleagues interpret the findings as showing that repeated low-dose psilocybin was associated with reduced perceived OCD symptom severity in this case, but did not improve performance on a task intended to measure cognitive flexibility. They argue that the healthy twin performed better on the set-shift task, yet they also stress that this difference cannot be attributed confidently to psilocybin because many confounding factors are present, including differences in diagnoses, histories, and concurrent treatments. The authors suggest several possible explanations: the OCD itself may underlie the cognitive flexibility deficit; low-dose psilocybin might not enhance, and could possibly impair, some aspects of cognition; or psilocybin may primarily facilitate the application of previously learned coping strategies rather than novel problem-solving. The paper places these findings in the context of earlier research that has reported both positive and negative effects of psilocybin on cognition. The authors note that some studies have suggested benefits for cognitive flexibility or creativity, whereas other work in healthy participants has reported possible cognitive costs, and preclinical studies have shown mixed effects depending on dose and task. They also relate their observations to previous clinical studies in OCD that found symptom reductions with psilocybin, including low-dose exposures. Key limitations are emphasised. These include the absence of a true baseline measurement for case X before psilocybin use, the self-administered and unstandardised dosing, possible variability in product quality, inability to quantify prior doses, the single-case design with twin comparison only, reliance on self-report, lack of biological or neuroimaging measures, short follow-up, and the presence of other treatments and expectancy effects that make it difficult to isolate the role of psilocybin. The authors conclude that the observed symptom relief alongside persistent cognitive deficits suggests low-dose psilocybin may not address all aspects of OCD pathology and that larger, more rigorous studies are needed. They specifically mention the potential value of randomised placebo-controlled trials, neuroimaging, comparative studies against SSRIs and CBT, and longitudinal work to evaluate safety and durability.
The authors conclude that, in this observational case of identical twins, low-dose psilocybin was associated with reduced perceived OCD symptoms and improved quality of life, but did not normalise cognitive flexibility in the affected twin. They suggest that psilocybin may perhaps work by helping patients apply therapeutic techniques such as acceptance and mindfulness more effectively in daily life, but they present this as speculative. The paper ends by calling for more rigorous randomised studies and longer-term investigations to clarify mechanisms, safety, and whether low-dose psilocybin should be considered as an adjunct or alternative to existing OCD treatments.
Case X is a male artist (painter) in his forties (40 years old at the time of interview) who has suffered from severe OCD most of his life. Case X was diagnosed with severe OCD (by a psychiatrist in the Danish healthcare system) in his early twenties, and later with a comorbid Attention Deficit Disorder (ADD), while the nature of the OCD obsessions was not disclosed, the nature of his compulsions was of the pure-O type. The OCD diagnosis was confirmed by the study team doing interview using the ICD-10 guidelines. Despite numerous attempts at recovery, different therapies and medications, including SSRIs (brand and dose was not disclosed), nothing has been efficacious in reducing his symptoms of OCD. While the case received prescription of methylphenidate (Ritalin, below 80 mg as per described in the Danish treatment guidelines) that effectively reduced symptoms of ADD, his symptoms of OCD were unaffected. In 2020, case X started self-administering low-doses of psilocybin on a one-day on, two-days off schedule (the dose of active psilocybin was later confirmed to be between 1-5 mg per dose described below), in addition to prescribed methylphenidate and self-taught acceptance and commitment (ACT) based therapy and mindfulness therapy. Case X was in out-patient treatment, his primary practitioner did not participate in this report. Following this combination of medications for several months (as he recalls it took 6 months before the symptoms were reduced to a level noticeable by others), his OCD symptoms gradually attenuated, to the point where he now after 2 years described himself as free from OCD, while he continues to take psilocybin. However, as we did not know Case X before he started microdosing, these effects remain anecdotal. Before psilocybin, case X would be deemed treatment-resistant (39) (Treatment-resistant OCD can be defined as adequate trials of firstline therapies without achieving a satisfactory response). Today he describes himself as nearly symptom-free, as indicated by a score of less than 21 assed doing our interview, on the Obsessive Compulsive Inventory-Revised (OCI-R), generally a score of above 40 indicates OCD. When asked about the causes of this dramatic improvement, case X attributes it to a combination of several factors. Firstly, he is adamant that the psilocybin has made it easier for him to withstand his obsessions and compulsions; that it has made them easier to manage. Case X does, however, emphasize that he believes that psilocybin on its own would not have reduced his OCD symptoms, but that it is efficacious in combination with his therapy. Case x did not report any adverse effects of psilocybin, despite the stigmatization "are you taking drugs" and the anxiety of obtaining psilocybin on the illegal marked. Case Y is case X's identical twin, a special needs teacher and, as expected with striking similarities to case X, considering both personality and behavior. Case Y has a wife and child whom he lives with and works within the health sector. Case Y and his twin brother grew up together and had a similar upbringing up until their early twenties. Case Y has also struggled with mental disorders, bipolar disorder, previously in his life, but not OCD and is currently considered healthy. When asked about how he would describe how low-dose psilocybin had affected his brother's OCD symptoms, he responded in a way that closely mirrored his brother. He underlined that there were varied factors that contributed to his brother's recovery, including psychotherapy and mindfulness therapy, in addition to psilocybin. Case Y expressed that he believes his brother's improvement was largely due to the combination and synergistic effects of psilocybin and treatment. Case Y was impressed that his brother had shown significant relief of symptoms in a short period of time and now demonstrates a more optimistic perspective on his prognosis and his ability to cope with his OCD. 2 Methods and results
Patient stated that he started using approximately 1 gram of hallucinogenic truffles sourced on the grey market then after a while switched to homegrown psilocybin mushrooms, which were grinded and dispersed in capsules containing approximately 0.1g each. Truffles are in general found to contain between 0.6 and 1.6 mg of psilocybin. A sample of the homegrown mushrooms were provided to the authors. Alkaloid content were extracted in methanol along with psilocin-d10, diluted with water, and analyzed using LC-MS as described previously. The home-grown mushrooms contained 3.9 mg psilocybin and 5.3 mg psilocin per capsule. 3 mg psilocybin are considered the threshold for perception when comparing the occupancy at 5-HT 2A receptors induced by psilocybin with the perceived psychedelic effect (42).
The twins were administered the 3D Inter-extra dimensional set shift task (IED) and a qualitative interview. The IED is a neuropsychological test aimed at assessing cognitive flexibility, it has commonly been used to assess neurological and psychological disorders, including attention deficit disorders, autism spectrum disorder, and OCD. IED is a computerized adaption of the wellknown Wisconsin Card Sorting Test, requiring participants to discriminate between stimuli and categorize them into sets. The objective of IED is to examine the participant's ability to adapt their responses flexibly based on either punishing or rewarding feedback. During the test, the participants are presented with several different stimuli, including different shapes, colors and number of figures. The stimuli are presented in two out of four different dimensions on the screen, and the participant must learn to categorize the stimuli based on a specific feature, as for example shape. The test moves through seven stages with stage 7 being the hardest. Case X, the twin with OCD, attempted to complete more trials (Case X: 48 vs Case Y: 19), but also made more errors (Case X: 25 vs Case Y: 8) in stage 7 of the test. This suggests more difficulty in completing stage 7 and thus impaired cognitive flexibility in the OCD affected twin.
In this study, we have examined cognitive flexibility in two twin brothers, one twin self-medicated his OCD with low-doses of psilocybin and one twin was considered healthy, using a set shift learning task. The results showed that the healthy twin brother, case Y, needed fewer trials to complete the test and made fewer errors throughout the test. Although interesting, there are many confounding factors such as his brother's diagnoses, medications and differing past histories that do not allow us to determine the leading factor. Firstly, these results show that there are obvious differences in performance, even though the cases are twins and considered to perform quite similarly on such a test, barring any large differences in their environment or epigenetic changes. This is not the case, however. A possible explanation could be, as other studies (10-12) also have argued, that OCD causes impairments in cognitive flexibility, and that this is the reason for the differences in performance or that the practice of self-administration of low-doses psilocybin does itself induce deficits in cognitive flexibility. Although most anecdotal reports indicate that low-doses of psilocybin can increase cognitive flexibility, there are studies that suggest the opposite. A recent study by Cavanna and colleagues found in their study that the practice of low-doses psilocybin could cause impairments in cognitive functions, including negative effects on attention and decision-making. The study, however, was performed on healthy individuals with no evident impairments in cognitive flexibility. The study could, thus, not be representative of a population where cognitive flexibility is impaired, such OCD patients. Another study in rats, also showed that high doses of psilocybin impaired immediate cognitive flexibility in a three-choice reversal learning task. It can therefore be argued that the possible adverse effects psilocybin has on cognition do not adequately explain the differences in performance between the twins. Another study found that low-doses, improved creativity. Case X took up painting, which may be an indication of increased creativity in his case. A possible explanation could be related to the performance on the extra-dimensional shift stage 7. Case X needed noticeably more trials to complete this stage and made more mistakes, compared to Case Y (Figure). At the extra-dimensional stage, the cases are required to make a substantial change in perspective, which relies on cognitive flexibility. Case X's poor performance at this stage indicates that he may have gotten stuck in rigid thinking patterns and did not attempt novel problem-solving strategies. This could, imply that low-doses of psilocybin would not facilitate cognitive flexibility. In a recent study by Pacheco and colleagues they examined how the acute effects of psilocybin affect cognitive flexibility in rats. The results showed that psilocybin caused vast improvements in cognitive flexibility, but only when the rats were switching to behavioral strategies that had previously been learnt. The study by Pacheco and colleaguesdoes therefore imply that psilocybin does not facilitate novel problem-solving strategies, which are required at the extra-dimensional shift stage, but could make it easier to apply previously learnt strategies to novel situations. It is therefore possible that the facilitated utilization of previously learnt problem-solving strategies could have interfered with the case's ability to attempt novel problem-solving strategies. Consequently, this would lead to poor performance on the extradimensional shift stage, as is the case with Case X. It is important to emphasize that this is speculative; nevertheless, it merits consideration as a promising pathway for future research. This case study has several limitations that must be considered. First, the lack of a real-baseline assessment of Case X in both questionnaire and cognitive test is a limitation, while we did try to correct for this by included the comparison, his unaffected identical twin, Case Y. The self-administered nature of psilocybin low-doses introduces variability in dosing, adherence, and potential placebo effects, limiting the generalizability of the findings. It is almost impossible to know if the grey market products were of the same batch and same quality. We cannot quantify prior doses. Second, as a single-case design involving identical twins, the results may not be representative of the broader OCD population, requiring larger, more diverse samples to confirm these observations. Additionally, the study relies on qualitative self-reports and standard symptom Total trials and errors made through the seven stages by either case X (OCD twin) or Y (healthy twin). assessments, which, while informative, lack objective biological markers or neuroimaging data to validate changes in brain function. The short-term nature of the study also prevents conclusions about long-term safety, efficacy, or potential adverse effects. Furthermore, the affected twin had a history of using other treatments, including methylphenidate and possibly other behavioral therapies, making it difficult to isolate the specific effects of low-doses of psilocybin and expectancy bias cannot be ruled out. Finally, while symptom relief was observed, persistent cognitive flexibility deficits might suggest that psilocybin low-doses may not fully address all aspects of OCD pathology, highlighting the need for further investigation into combination therapies or adjunctive interventions.
When discussing his compulsions after the low-doses regimen case X mentioned: "It will also be much easier, in my opinion, with psilocybin to learn to accept, it was difficult before. You can also learn to accept, and there are many who can say they can learn to accept, I could do that too, but you accept something that is very unpleasant still. With the psilocybin, you accept something that is very uncomfortable, and you are much freer. Before low-doses psilocybin, well it's fine, I can accept and everything and it's nice, it's also liberating when you learn that technique, I've tried that, it was a relief but still a huge struggle". "Especially with regards to quality of life, because when you accept, you feel an extreme discomfort. With psilocybin this discomfort gets much smaller". "Psilocybin makes you feel your own self; you can move a lot more; you don't do that with the SSRIs. You don't get that perception that you feel yourself in a different way, it's a completely different experience, it's like you're coming to yourself again, you're gaining self-respect somehow, SSRIs cannot do that". "The experience of being 100% free of OCD occurs in periods, and the periods, over the last 3-4 months, increased from 1 to 2 days, they get longer and longer. It's a small miracle".
A crucial question that remains is how the results from the IED can be related to the attenuation of OCD symptoms experienced by Case X. Essentially, the results indicate that while low-doses of psilocybin reduced perceived symptoms they did not improve performance in the extra-dimensional set shifts. As such low-doses of psilocybin may not increase cognitive flexibility and may not target the full symptomatology of OCD, as also described be Pellegrin et al. in their recent clinical trial with a single 10 mg dose. An individual with OCD may be accustomed to alleviating distressing feelings by engaging in compulsive behaviors, but after psilocybin, may attempt to accept the distressing feeling rather than suppress them be compulsive behaviors. This would be an extradimensional shift, and an attempt at novel problem-solving strategies. If low-doses of psilocybin, in fact, make it harder to perform such shifts, it would not be advantageous to OCD patients, and could make it more difficult to break out of repetitive patterns. This is, however, quite the contradiction to case X's experience with psilocybin, who is adamant that it has helped him. A possible explanation could be related to Pacheco and colleagues' (2023) findings: That psilocybin makes it easier to apply previously learnt problem-solving strategies to novel situations. As mentioned, Case X took part in mindfulness and acceptance therapy simultaneously with the low-doses practice, where he learned new ways to manage his OCD. It is possible that psilocybin made it easier for him to apply these techniques to novel situations in his everyday life, consequently helping him break out of the repetitive OCD cycle.
An avenue of research that has gained a lot of traction in recent years is the use of psychedelics in the treatment of mental disorders, including psilocybin. Through both interviews and a reversal learning test, we aimed to examine the effects that low-doses of psilocybin have on cognitive flexibility. It is. however, important to clarify that the object of this study was not to establish any causality, only to gather some preliminary data on a subject that lacks comprehensive understanding. The results indicated that lowdoses of psilocybin did not amend the cognitive flexibility deficits in the case with OCD yet still made it easier to overcome OCD symptoms and increase his quality of life. A potential role for lowdoses of psilocybin could be to facilitate the use of techniques learnt in psychological therapy making them more efficacious. Albeit speculative, it merits consideration as a potential pathway for future research to investigate further. Future investigations into the therapeutic potential of low-dose psilocybin for OCD should prioritize methodological sound randomized, placebo-controlled trials. Neuroimaging techniques, such as fMRI and EEG or MEG, will be essential for elucidating the mechanisms of action within OCD-related neural circuits. Comparative effectiveness studies against established treatments, including SSRIs and CBT, are necessary to determine if psilocybin can be a replacement or adjunct with current therapies. Longitudinal studies are required to comprehensively evaluate the safety profile, sustained efficacy, and longterm impact of psilocybin treatment. Furthermore, given the observed persistence of cognitive flexibility deficits despite symptom reduction, research should explore adjunctive therapies to address the cognitive effects.
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