Clinical TrialAnxiety DisordersMDMAPlaceboPlaceboPlaceboPlaceboNot yet recruiting

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.

Target Enrollment
156 participants
Study Type
Phase III interventional
Design
Randomized, single Blind

Detailed Description

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.

Study Protocol

Preparation

3 sessions
90 min each

Dosing

2 sessions
480 min each

Integration

8 sessions
90 min each

Therapeutic Protocol

cbt

Study Arms & Interventions

MDMA-assisted

experimental

Manualised CBT-informed MDMA-assisted psychotherapy; two dosing sessions with preparatory and integration therapy.

Interventions

  • MDMA1 - 1.5 mg/kg
    via Oral• two sessions• 2 doses total

    Session 1 initial 1.0 mg/kg with 0.5 mg/kg supplemental at 2.5–3 h if indicated; Session 2 initial 1.5 mg/kg if Session 1 well tolerated, otherwise 1.0 mg/kg; supplemental 0.5 mg/kg; doses rounded to nearest 40 mg, max initial 120 mg.

Dexamfetamine-assisted

active comparator

Dexamfetamine with same psychotherapy schedule as MDMA arm.

Interventions

  • Placebo20 mg
    via Oral• two sessions• 2 doses total

    Session doses: 20 mg initial, 10 mg supplemental at 2.5–3 h if indicated.

Diphenhydramine-assisted

active comparator

Diphenhydramine with same psychotherapy schedule.

Interventions

  • Placebo50 - 75 mg
    via Oral• two sessions• 2 doses total

    Session 1 initial 50 mg (0 mg supplemental); Session 2 initial 75 mg (0 mg supplemental).

Lorazepam-assisted

active comparator

Lorazepam with same psychotherapy schedule.

Interventions

  • Placebo2 - 3 mg
    via Oral• two sessions• 2 doses total

    Session 1 initial 2 mg; Session 2 initial 3 mg; no supplemental doses.

Placebo-assisted

inactive

Placebo capsules with same psychotherapy schedule as MDMA arm.

Interventions

  • Placebo
    via Oral• two sessions• 2 doses total

    Matching placebo capsules during dosing sessions.

Participants

Ages
16 – 25
Sexes
Male & Female

Inclusion Criteria

  • 1. 16–25 years old at consent;
  • 2. ASD diagnosed in the past year or as assessed with the Autism Diagnostic Observation Schedule, 2nd Edition (ADOS-2) Module 4;
  • 3. Current diagnosis of DSM-5 Social Anxiety Disorder (using the SCID-5);
  • 4. Ability to provide informed consent (sufficient English and IQ > 70 assessed with the Wechsler Test of Adult Reading).

Exclusion Criteria

  • 1. Unable to safely abstain from alcohol for 48 hours before medication-assisted therapy sessions;
  • 2. Unable to abstain from cannabis for 48 hours before medication-assisted therapy sessions;
  • 3. Use of any illicit drug other than cannabis on average > 2 days per week over the past 4 weeks at screening;
  • 4. Unstable medical conditions or contraindications for study medications, assessed with medical exam, electrocardiogram, and clinical blood tests, and as determined by the trial doctor;
  • 5. Current treatment with contraindicated medications that cannot be safely discontinued as determined by the trial doctor;
  • 6. Current or past DSM-5 psychotic or bipolar illness, as assessed by the SCID-5;
  • 7. Acute suicidality or severe disturbance likely to interfere with the ability to comply with the study protocol;
  • 8. Significant speech, visual, or auditory impairment likely to interfere with treatment;
  • 9. Pregnancy, breastfeeding or, if sexually active, no effective contraception (participants capable of becoming pregnant only).

Study Details

Locations

Unknown facility — Australia

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