PsilOCD: A Pharmacological-Challenge Feasibility Study
- Registration Number
- NCT06258031
- Lead Sponsor
- Imperial College London
- Brief Summary
The purpose of this study is to assess the impact of psilocybin on cognitive inflexibility and neural plasticity in a cohort of people with obsessive-compulsive disorder (OCD).
- Detailed Description
This mechanistic study will utilise a within-subjects design, administering up to 10mg of psilocybin to participants with OCD (DSM-5 criteria) on two separate instances spaced four weeks apart. To ensure consistency and participant safety, dosing will occur under medical supervision with psychological support from two experienced therapists. Before and after each session, participants will engage in virtual preparation and integration sessions led by their therapists. Cognitive tasks will be administered in the days following each dosing session. Additionally, acute post-dosing EEG recordings will be conducted, and blood samples will be taken after each dosing session. OCD symptoms will also be assessed seven times throughout the trial by an external blinded psychiatrist, serving as a secondary outcome. Collectively, these measures aim to evaluate changes in cognitive inflexibility, decision-making abilities, neuroplasticity (peripheral blood markers and EEG measures), inflammation (peripheral blood markers), and symptomatology following each dosing session.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 19
- Aged 20 to 65 years;
- Any gender;
- A primary diagnosis of OCD (based on the Mini-International Neuropsychiatric Interview (M.I.N.I.));
- Has met diagnostic criteria for OCD for at least 12 months;
- Willing to comply with protocol and associated lifestyle restrictions;
- Adequate understanding of the English language to give informed consent and participate in the study;
- Participant can attend visits as an outpatient;
- Comfortable using a computer, access to internet from home, and willing to participate in some of the study visits via video-link.
Key
- Current or past history of dependent (according to ICD10 criteria) substance use (not including nicotine and/or caffeine), Tourette's syndrome, autism spectrum disorder, epilepsy, organic mental disorder, or a personality disorder apart from obsessive-compulsive personality disorder;
- Current or past history of psychosis or mania in themselves or a first-degree relative;
- Unstable physical health;
- Significantly abnormal clinical test result;
- Heavy smoker, or unable to attend the dosing days (including the subsequent recovery part) without a smoking break;
- Unwillingness to allow their GP or mental health practitioners to be informed of their participation (or, to allow study team access to Summary Care Record).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description All participants Psilocybin (COMP360) Up to 10mg of psilocybin on two separate dosing days (separated by 4 weeks)
- Primary Outcome Measures
Name Time Method Intradimensional-extradimensional (ID-ED) set shift 4 weeks Scores on this neurocognitive task administered as part of the Cambridge Neuropsychological Test Automated Battery (CANTAB). ID-ED performance is an established measure of cognitive inflexibility in OCD (Chamberlain et al., Am J Psychiatry, 2007), with worse scores corresponding to decreased flexibility.
The visual long-term potentiation (vLTP) electroencephalogram (EEG) paradigm (acute quantified changes in neuroplasticity in the visual system). 8 weeks We will assess acute changes in homosynaptic neuroplasticity using the visual long-term potentiation (vLYTP) EEG paradigm. In this paradigm, we induce neural plasticity in the occipital cortex by exposing participants to visual stimuli of varying frequencies. This task specifically quantifies homosynaptic plasticity because it triggers changes in neighbouring neurons within the occipital cortex.
- Secondary Outcome Measures
Name Time Method Oura: heart-rate variability 8 weeks Participants will be given an Oura ring to keep track of heart-rate variability (HRV) throughout the duration of the study (participants will not be able to see their own data).
Measures of depression symptoms including the Montgomery-Åsberg Depression Rating Scale (MADRS) 8 weeks Higher scores correspond to worse depressive symptoms
Clinical measures of compulsivity of relevance to OCD including Yale-Brown Obsessive Compulsive Scale (Y-BOCS) 8 weeks Assess OCD symptoms over the study's duration (with higher scores corresponding to worse symptoms in all scales mentioned)
Measures of the acute psychological effects of psilocybin including the Emotional Breakthrough Inventory 4 weeks Higher scores correspond to greater subjective emotional changes elicited by the acute psilocybin experience
Oura: sleep stages 8 weeks Oura rings will also measure the number of minutes/hours spent in each sleep stage (awake, light, deep, and rapid eye movement (REM))
Cognitive measure: Information-seeking task 4 weeks It tests participants' confidence and ability to make decisions involving uncertainty by monitoring their tendency to seek extra information (recently developed by Lion Schulz and colleagues, 2020)
Measures of anxiety symptoms including the State-Trait Anxiety Inventory (STAI) 8 weeks Higher scores correspond to worse anxiety-related symptoms
Oura: REM sleep 4 weeks Examines acute changes in neuroplasticity. Participants detect subtle colour changes while listening to sound sequences, triggering an EEG signal increase in the auditory cortex. This measures the brain's ability to induce repetition suppression across consecutive trials, reflecting its capacity to adapt to expected sound sequences over time.
Cognitive measure: Reversal learning task (administered as part of the Cambridge Neuropsychological Test Automated Battery (CANTAB)) 4 weeks Assesses ability to adapt to changing contingencies; higher scores indicate better cognitive flexibility
Cognitive measure: Visuospatial memory paired-associates learning task (administered as part of the Cambridge Neuropsychological Test Automated Battery (CANTAB)) 4 weeks Serves as a control task; higher scores indicate better visuospatial memory faculties
Acute plasma serum concentration of Brain-Derived Neurotrophic Factor (BDNF) 4 weeks BDNF concentration (pg/mL) serves as a biomarker with significant functions in brain health, neuroplasticity, and the regulation of inflammation.
Trial Locations
- Locations (1)
CIPPRes Clinic
🇬🇧London, United Kingdom