PAPAYA: Pharmacologically-Assisted Psychotherapy for social Anxiety in Young people with Autism
This randomised, blinded, Phase III trial (n=156) will investigate MDMA-assisted psychotherapy (weight-based dosing with supplemental doses) versus dexamfetamine-, lorazepam-, diphenhydramine-, or placebo-assisted psychotherapy for social anxiety in autistic young people.
Details
Randomised, parallel-group trial comparing MDMA-assisted psychotherapy with three active comparator medications and placebo; n=156, two 8-hour medication-assisted therapy sessions with preparatory and integration psychotherapy.
Therapy is manualised and adapted from CBT for social anxiety in autism: three 90-minute preparatory sessions, two 8-hour dosing sessions separated by 4 weeks, and eight 60–90 minute integration sessions (four after each dosing session). Sessions delivered primarily face-to-face with limited telehealth for some prep/integration sessions.
MDMA dosing is weight-based (initial 1.0 mg/kg with 0.5 mg/kg supplemental; second session 1.5 mg/kg if first tolerated, otherwise 1.0 mg/kg; supplemental 0.5 mg/kg); doses rounded to nearest 40 mg, max initial 120 mg. Comparator dosing: dexamfetamine 20 mg (±10 mg supplemental), diphenhydramine 50→75 mg, lorazepam 2→3 mg; placebo given as matching capsules.
Study sites: Orygen Clinical Trials Unit (Melbourne) and Brain and Mind Centre (University of Sydney). Training and fidelity procedures include video recording (with permission) and study-specific clinician training delivered by study PIs.