This randomised, blinded, Phase III trial (n=156) will investigate the effects of MDMA-assisted psychotherapy (70mg/70kg, with a 35mg/70kg supplemental dose; 105mg/70kg in the second session if well tolerated, otherwise 70mg/70kg, with a 35mg/70kg supplemental dose; doses rounded to the nearest 40 mg, max 120 mg initial dose) on social anxiety in young autistic people, compared with psychotherapy assisted by dexamfetamine (20mg, with a 10mg supplemental dose), lorazepam (2mg, with a 3mg dose in the second session), diphenhydramine (50mg, increasing to 75mg), or placebo.
Participants, aged 16-25 years, will undergo a structured psychotherapy programme based on cognitive behavioural therapy (CBT). This includes three preparatory sessions, two 8-hour medication-assisted therapy sessions (four weeks apart), and eight post-session integration therapy sessions. The study will take place at the Orygen Clinical Trials Unit in Melbourne and the Brain and Mind Centre at the University of Sydney.
The primary outcome measure is the Leibowitz Social Anxiety Scale (LSAS), assessed at 12 weeks, with secondary outcomes including safety, depression, social skills, and quality of life. This trial is funded by the Australian Department of Health and Aged Care Medical Research Future Fund and is led by Associate Professor Gill Bedi at Orygen.
Trial Details
Individual psychotherapy is manualized and adapted from Cognitive Behavioral Therapy for social anxiety in autism. Participants undergo three 90-minute preparatory psychotherapy sessions, approximately a week apart. Following the prep sessions, each participant will attend two 8-hour MDMA-assisted psychotherapy sessions separated by 4 weeks. There will be four 60-90 minute integration psychotherapy sessions in the 4 weeks after each MDMA session, equalling a total of 8 integration sessions. Therapy is delivered by allied health practitioners (e.g. psychologists) trained in this method. MDMA-assisted sessions and most other psychotherapy sessions are delivered face-to-face. Some preparatory and/or integration sessions may be delivered via telehealth. Preparatory sessions will focus on developing a collaborative relationship between participant and therapist, setting therapy expectations and developing a safety plan. Medication-assisted psychotherapy sessions will include periods of quiet introspection and will employ the cognitive behavioural framework to discuss material arising during these periods, as well as reflecting on cognitions identified as related to social anxiety, and some exposure activities. Integration sessions will include reflecting on experiences and learnings in the medication-assisted sessions and generalising these learnings into everyday life using cognitive behavioural techniques. MDMA DOSE: Session 1, Initial Dose 1.0 mg/kg (Administered at the beginning of the session once baseline checks (e.g., medical review; biochemical tests for pregnancy and recent drug and alcohol use; adverse events) are completed; oral) Session 1, Supplemental Dose 0.5mg/kg (Administered 2.5-3 hours post initial dose if indicated; oral) Session 2, Initial Dose 1.5 mg/kg if Session 1 dose well tolerated, or 1.0 mg/kg (Administered at the beginning of the session once baseline checks (e.g., medical review; biochemical tests for pregnancy and recent drug and alcohol use; adverse events) are completed; oral) Session 2, Supplemental Dose 0.5mg/kg (Administered 2.5-3 hours post initial dose if indicated; oral) MDMA doses are rounded to the nearest 40 mg with a maximum initial dose of 120 mg. STUDY SETTING The study will be conducted at Orygen Clinical Trials Unit in Melbourne and the Brain and Mind Centre at the University of Sydney. FIDELITY All participants will be asked for permission to video record sessions for ongoing clinician training and fidelity assessment. ALLIED HEALTH PRACTITIONERS All therapists will be clinically experienced allied health providers. Study specific clinician training will be delivered by study PIs who are experts in the field (clinical psychologists and psychiatrists). Training (between five and ten, 2-hour training sessions) will include didactic training, guided reading, discussion, and role plays and be delivered before the first trial participant is randomised.Trial Number ACTRN12624001474549p