Developing Optimal Psychedelic Assisted Psychotherapy for Obsessive-Compulsive Disorder

INTERVENTION: MDMA + Exposure Response Prevention Intervention: Session plan – minimum of 2 preparation sessions, 3 MDMA sessions (2‐6 weeks apart), 4 integration sessions, for example: Week 1 Preparation session 1 Week 2 Preparation session 2 Week 3 MDMA 1 + integration session 1 Week 4 Preparation session 3 (optional) Week 5 MDMA 2 + Integration session 2 Week 6 Preparation session 4 (optional) Week 7 MDMA 3 + Integration session 3 Week 8 Integration session 4 The therapists conducting these sessions are health/healing professionals (doctor, psychiatrist, psychologist, psychotherapist, counsellor, nurse) trained in the administration of psychedelic assisted psychotherapy. Adherence will be recorded electronically through a session attendance checklists as part of their study file. Overview of 2 Xpreparation sessions for MDMA: There will be a minimum of two 90‐minute preparation sessions conducted remotely or in person with a therapist. There also will be an opportunity for participants to engage in an optional preparation session prior to the second and third medication session. The participant will have the opportunity to meet the therapists/staff who will be present in the MDMA dosing session prior to dosing, during this preparation phase (more preparation sessions will be provided if deemed necessary by the therapist). Preparation session 1: Alliance development and formulation: the primary aims of the initial session will be the development of a therapeutic alliance, build trust and safety between the study therapists and the participant. Clarify participant intentions for the MDMA session, anxieties and hopes for the experience. Discuss ethical considerations and participant choices CONDITION: Mental Health ‐ Other mental health disorders Treatment Resistant Obsessive‐Compulsive Disorder; ; Treatment Resistant Obsessive‐Compulsive Disorder PRIMARY OUTCOME: Total score on the Yale‐Brown Obsessive‐Compulsive Scale (YBOCS).[Baseline compared to study timepoints: Post Drug therapy session 1, Post Drug therapy session 2, Post Drug therapy session 3, End Integration Therapy (8 weeks post‐baseline) (primary timepoint), and 1, 3 and 6 months post‐integration therapy completion] INCLUSION CRITERIA: Diagnosis of Obsessive‐Compulsive Disorder, in accordance with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM‐5) 25‐65 years of age. Treatment resistant symptoms: For OCD: failure to tolerate or respond to at least 2 trials of adequate medication therapy (SSRI or clomipramine) at minimum effective therapeutic dose for at least 8 weeks Moderate – severe symptoms: For OCD: YBOCS score of >13 Demonstrated capacity to give informed consent Willingness and capacity (as judged on assessment by study clinicians) to engage in the therapeutic elements of the study protocol SECONDARY OUTCOME: 12 Item World Health Organisation Disability Assessment Schedule (WHODAS 2.0)[Baseline compared to study timepoints: End Integration Therapy (8 weeks post‐baseline), and 6 months post‐integration therapy completion] A Go/NoGo task to assess response inhibition[Baseline EEG (pre psilocybin or MDMA session) compared to study timepoints: Post Drug therapy session 1 and Post Drug therapy session 3.] A Latent Inhibition task to assess the personality trait of openness[Baseline EEG (pre psilocybin or MDMA session) compared to study timepoints: Post Drug therapy session 1 and Post Drug therapy session 3.] Arrow version of Eriksen Flanker Task to assess reaction time, where longer reaction times correspond to greater attentional processing time, and accuracy rate where greater accuracy is assumed to be related to a better allocation of attentional resources[Baseline EEG (pre psilocybin or MDMA session) compared to study timepoints: Post Drug therapy session 1 and Post Drug therapy session 3.] Assessment of Quality of Life (AQoL‐6D)[Baseline compared to study timepoints: End Integration Therapy (8 weeks post‐baseline), and 6 months post‐integration therapy completion] Blinding Questionnaire designed specifically for this study to measure blinding[Conducted 3 Days Post Drug therapy session 1, 3 Days Post Drug therapy session 2, 3 Days Post Drug therapy session 3, and End of Integration Therapy (8 weeks post‐baseline)] Depression, Anxiety and Stress Scale (DASS10)[Baseline compared to study timepoints: End Integration Therapy (8 weeks post‐baseline), and 6 months post‐integration therapy completion] Generalised Anxiety Disorder (GAD‐7)[Baseline compared to study timepoints: End Integration Therapy (8 weeks post‐baseline), and 6 months post‐integration therapy completion] Patients Global Impression of Improvement Scale (PGI‐I) [End Integration Therapy (8 weeks post‐baseline) compared to study timepoints: 1, 3 and 6 months post‐integration therapy completion] Side effects questionnaire designed specifically for this study to measure any side effects from the treatment session. [Conducted 3 Days Post Drug therapy session 1, 3 Days Post Drug therapy session 2, 3 Days Post Drug therapy session 3, and End of Integration Therapy (8 weeks post‐baseline)] Ten minutes of eyes closed resting EEG data to assess excitation/inhibition balances[Baseline EEG (pre psilocybin or MDMA session) compared to study timepoints: Post Drug therapy session 1 and Post Drug therapy session 3.] The Acceptance and Action Questionnaire (AAQ‐2)[Baseline compared to study timepoints: End Integration Therapy (8 weeks post‐baseline), and 6 months post‐integration therapy completion] The Mystical Experience Questionnaire (MEQ)[End of Integration Therapy (8 weeks post‐baseline) compared to study timepoint: 6 months post‐integration therapy completion] The patient global impression of severity (PGI‐S)[Baseline compared to study timepoints: End Integration Therapy (8 weeks post‐baseline), and 1, 3 and 6 months post‐integration therapy completion] The Watts Connectedness Scale[Baseline compared to study timepoints: End Integration Therapy (8 weeks post‐baseline), and 6 months post‐integration therapy completion] Total score on the Self‐rated version of the Montgomery Asberg depression rating scale [Baseline compared to study timepoints: Post Drug therapy session 1, Post Drug therapy session 2, Post Drug therapy session 3, End Integration Therapy (8 weeks post‐baseline), and 1, 3 and 6 months post‐integration therapy completion] Treatment acceptability and tolerability questionnaire designed specifically for this study to measure treatment acceptability and tolerability[Conducted 3 Days Post Drug therapy session 1, 3 Days Post Drug therapy session 2, 3 Days Post Drug therapy session 3, and End of Integration Therapy (8 weeks post‐baseline)]