Feasibility, Clinical Effects, and Safety of Psilocybin-assisted Psychotherapy for Treatment-resistant OCD

Inclusion Criteria: * Adults 18 to 65 years old; * Are outpatients * Must be deemed to have capacity to provide informed consent; * Must sign and date the informed consent form; * Stated willingness to comply with all study procedures; * Ability to read and communicate in English, such that their literacy and comprehension is sufficient for understanding the consent form and study questionnaires, as evaluated by study staff obtaining consent; * Primary The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of obsessive compulsive disorder (OCD) based on medical records and assessment using the Structured Clinical Interview for DSM-5 (SCID-5) administered at the first screening visit; * Participants diagnosed with treatment-resistant OCD defined as individuals with a score of ≥ 16 on the YBOCS (i.e. moderate symptom severity) and that have not responded to two or more separate pharmacological interventions and one or more trials of cognitive behavioural therapy (CBT); there is no upper limit on the number of treatment failures; * Individuals with an estimated glomerular filtration rate (eGFR) above 40mL/min/1.73m2 and all blood work within normal limits as assessed by clinical laboratory tests at Screening (V1) * Ability to take oral medication; * Individuals who are capable of becoming pregnant: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation; * Individuals who are willing to and have tapered off current OCD medications for a minimum of 2-weeks prior to Baseline (V2) and whose physician confirms that it is safe for them to do so; * Individuals who are willing to and have tapered off current inhibitors of 5'-diphospho-glucuronosyltransferase (UGT)1A9 and 1A10, aldehyde dehydrogenase inhibitors (ALDHs) and alcohol dehydrogenase inhibitors (ADHs) for a minimum of 2-weeks (or more depending on the medication) prior to Baseline (V2) and for the duration of the study and whose physician confirms that it is safe for them to do so; and * Agreement to adhere to Lifestyle Considerations (section 4.5) throughout study duration. Exclusion Criteria: * Pregnant as assessed by a urine pregnancy test at Screening (V1) and Baseline (V2) or individuals that intend to become pregnant during the study or are breastfeeding; * Treatment with another investigational drug or other intervention within 30 days of Screening (V1); * Have initiated psychotherapy in the preceding 12 weeks prior to Screening (V1); * Have a DSM-5 diagnosis of substance use disorder (use of tobacco and prescribed opioids are permitted) within the preceding 6 months; * Have active suicidal ideation as determined by the C-SSRS and/or clinical interview. Significant suicide risk is defined by suicidal ideation as endorsed by items 4 or 5 of the C-SSRS; * Any DSM-5 lifetime diagnosis of a schizophrenia-spectrum disorder; psychotic disorder (unless substance induced or due to a medical condition), bipolar I or II disorder, paranoid personality disorder, borderline personality disorder, or neurocognitive disorder as determined by medical history and the SCID-5 clinical interview; * Any first-degree relative with a diagnosis of schizophrenia-spectrum disorder; psychotic disorder (unless substance-induced or due to a medical condition); or bipolar I or II disorder as determined by the family medical history form and discussions with the participant; * Have contraindications to transcranial magnetic stimulation (TMS) as determined by the transcranial magnetic stimulation adult safety screen (TASS) questionnaire; * Have a history of seizures; * Are taking anticonvulsants or benzodiazepines (Lorazepam up to 2mg/day is acceptable); * Presence of a relative or absolute contraindication to psilocybin, including a drug allergy, recent stroke history, uncontrolled hypertension, low or labile blood pressure, recent myocardial infarction, cardiac arrhythmic, severe coronary artery disease, or moderate to severe renal or hepatic impairment; * Use of classic psychedelic drugs within the previous 12 months; OR * Any other clinically significant physical illness including chronic infectious diseases or any other major concurrent illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if they take part in the study.