NCT06731621

Psilocybin for Treatment-Resistant Depression in Autism

Psilocybin for Treatment-Resistant Depression in Autism: a Pilot Trial With Pre-Post Brain and Cognitive Measurement to Understand Mechanism

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Centre for Addiction and Mental Health · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

We propose a first-of-its-kind open-label clinical trial to investigate the feasibility, tolerability, and safety of administering psilocybin in autistic adults with treatment-resistant depression (TRD). In this study, 20 participants (intellectually able and fluent-speech adults) with autism and co-occurring TRD will receive around 20 hours of manualized psychotherapy that has previously been used with psilocybin (Agin-Liebes et al., 2020). They will also receive psilocybin at 2 different time points, firstly a safety dose of 10mg, followed by a treatment dose of 25mg. This study design is in accordance with previous studies investigating the use of psilocybin with psilocybin-assisted therapy (PAT) to treat TRD (Carhart-Harris et al., 2016, 2018)

Detailed description

Each participant will begin with a screening visit (V1), during which eligibility will be determined through clinical and psychiatric assessments of the participant's physical and mental health. Following confirmation of eligibility, the study procedures will begin. The participant will begin with a 2-4 week tapering period during which they will taper and discontinue any conventional antidepressants. Most conventional antidepressants will require a minimum 2-week tapering period, with the exception of fluoxetine, which will require a 4-week tapering period. Additional time may be added at the discretion of the study investigator. During the tapering period, there will be weekly check-ins with a study psychiatrist by in-person assessment or brief telephone calls to monitor for worsening depression and suicidality. Following the tapering period, participant eligibility will be re-assessed for the eligibility. At Study Visit 2 (Baseline, V2), participants will complete a series of questionnaires and assessments (Table 2) and preparatory therapy with trained study therapists. The participant will also receive a brain MRI scan lasting for about 45 minutes. At Study Visits 3 \& 4 (V3/V4), participants will receive oral doses of psilocybin (safety dose of 10 mg at V3, treatment dose of 25 mg at V4), to assess the tolerability and efficacy of psilocybin. These sessions will be held one week apart and will last 6 to 8 hours each. These sessions will take place in a pre-decorated treatment room at CAMH. Throughout the entire duration of the dosing sessions, participants will be monitored by a minimum of two trained therapists. At the end of each session, participants will be evaluated for safety by a study psychiatrist before being discharged. Participants will also rate the 11-Dimension Altered States of Consciousness (11D-ASC) at the end of each dosing day when the subjective effects of psilocybin have subsided to a negligible level. In addition, the participant will also receive a second brain MRI scan lasting for about 30 minutes (V3a) following V3 Safety dosing. To reduce participant burden, MRI scan can be completed on the following day or within 1-3 days following safety dosing (V3). The participants will also be required to complete the self-rated questionnaires at this additional MRI assessment. Visit 5 (V5) will be held one day after administration of the treatment dose (V4). During V5 the participants will complete post-treatment clinical and cognitive assessments, alongside the third and final MRI scan (of the main clinical trial design). Participants will also undergo a 1-hour integration therapy session to debrief their experiences the day before. Visit 6 (V6) will be held one week following the treatment dose (V4). During V6 a second 1-hour integration therapy session takes place and all post-treatment clinical assessments will be repeated. Subsequent clinical progress will be evaluated virtually at V7, V8, V9, which will respectively be held 2, 4, and 12 weeks following the treatment session (V4). 10 participants out of 20 participants in the main clinical trial could opt to receive 7 additional brain MRI scans besides the MRI scans at V2, V3a and V5 required in the main clinical trial. These 7 additional scans will be assessed at V1, in the middle of medication washout/tapering period V6, V7, V8, 8 weeks following the treatment dose (V4), and V9, respectively. At each optional MRI visit, self-rated assessments will also be collected.

Conditions

• Treatment Resistant Depression
• Autism Spectrum Disorder

Interventions

Type	Name	Description
DRUG	Psilocybin	2 dosing sessions 1 week apart, each about 6-8 hours duration Psilocybin-assisted therapy (PAT), is a psychotherapeutic intervention in which the psychological effects of psilocybin play a significant role. PAT procedures typically involve psychological preparation prior to therapist-supported psilocybin dosing sessions. These sessions are used to establish a therapeutic relationship, inform participants about what to expect, and set expectations for the dosing session. During the psilocybin dosing session, trained therapists support the individual through their experience and psychological integration therapy occurs after the dosing experience. PAT has shown impressive antidepressant effects in people with TRD or severe MDD in at least six modern-era clinical trials (Andersen et al., 2021).

Timeline

• Start date: 2024-11-01
• Primary completion: 2027-08-01
• Completion: 2027-08-01
• First posted: 2024-12-12
• Last updated: 2026-03-20

Locations

1 site across 1 country: Canada