Clinical TrialTreatment-Resistant Depression (TRD)PsilocybinRecruiting

Psilocybin for Treatment-Resistant Depression in Autism With Pre-Post Brain and Cognitive Measurement to Understand Mechanisms (PAT-DA)

Open-label Phase I study (n=20) assessing feasibility, tolerability and safety of psilocybin (10 mg safety dose then 25 mg treatment dose) with manualised psilocybin-assisted therapy in autistic adults with treatment-resistant depression.

Target Enrollment
20 participants
Study Type
Phase I interventional
Design
Non-randomized

Detailed Description

This open-label single-group Phase I trial will enrol 20 intellectually able autistic adults with treatment-resistant depression to evaluate feasibility, tolerability and safety of two oral psilocybin dosing sessions (10 mg safety dose, then 25 mg treatment dose) given approximately 1 week apart.

Participants will receive around 20 hours of manualised psilocybin-assisted psychotherapy spanning preparation, dosing support and integration; outcome measures include clinical depression scales, cognitive and pre–post brain measures to explore mechanisms.

Study Protocol

Preparation

sessions
1200 min each

Dosing

2 sessions
480 min each

Integration

sessions

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

Open-label

experimental

Safety dose (10 mg) then treatment dose (25 mg) psilocybin with manualised psilocybin-assisted therapy; two dosing sessions ~1 week apart (~6–8 hours each).

Interventions

  • Psilocybin25 mg
    via Oral• two sessions 1 week apart• 2 doses total

    10 mg safety dose then 25 mg treatment dose; paired with ~20 hours of manualised psychotherapy; sessions ~6–8 h each.

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • Autistic adult, ages 18–65
  • Must be deemed to have capacity to provide informed consent
  • Must sign and date the informed consent form
  • Willingness to comply with all study procedures
  • Intellectually able: either documented IQ ≥70 on WAIS-IV GAI or equivalent, or >10th percentile on nine-item RSPM
  • Ability to read and communicate in English sufficient for consent and questionnaires
  • Primary DSM-5 diagnosis of non-psychotic MDD (single or recurrent) based on SCID-5-CV at screening
  • Treatment-resistant depression defined as baseline GRID-HAMD-17 > 14 and non-response to ≥2 adequate antidepressant trials (no upper limit on failures)
  • Ability to take oral medication
  • Individuals capable of becoming pregnant must use highly effective contraception for ≥3 months prior to screening and during participation
  • Willingness to taper off current antidepressant and antipsychotic medications for a minimum of 2 weeks (or longer as required) prior to baseline with physician approval
  • Agreement to adhere to lifestyle considerations during study

Exclusion Criteria

  • Exclusion Criteria:
  • Pregnant or breastfeeding or intending to become pregnant during the study
  • Treatment with another investigational drug or intervention within 30 days of screening
  • Unstable seizure disorder (not seizure-free for ≥6 months or unstable anticonvulsant treatment <4 weeks)
  • Any clinically significant or unstable medical condition (cardiovascular, liver, kidney, pulmonary disease, congenital brain malformation) per investigator assessment
  • Moderate or severe DSM-5 alcohol or substance use disorder in past 12 months
  • Any DSM-5 lifetime diagnosis of schizophrenia-spectrum disorder, psychotic disorder (unless substance-induced or medical), bipolar I/II, paranoid personality disorder, or neurocognitive disorder
  • Any first-degree relative with schizophrenia-spectrum disorder, psychotic disorder (unless substance-induced or medical), or bipolar I/II disorder
  • Contraindication to psilocybin (drug allergy, recent stroke, uncontrolled or labile BP, recent MI, arrhythmia, severe CAD, moderate–severe renal or hepatic impairment)
  • Substantial lifetime use (>10 years) or recent use (past 6 months) of ketamine, psychedelics, or MDMA
  • Any other clinically significant physical illness that may interfere with study or pose risk
  • Active suicidal ideation with intent and plan as determined by SBQ-ASC
  • Currently undergoing psychotherapy or received psychotherapy within 12 weeks prior to screening
  • Contraindication to MRI (metal implants, pacemaker, aneurysm clips, metallic tattoos on head, history of claustrophobia)

Study Details

Locations

Centre for Addiction and Mental Health — Toronto, Ontario, Canada

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