Psilocybin for Treatment-Resistant Depression in Autism

NCT06731621 | Recruiting Phase 1

• 1 other identifier: 2023/112
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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)

Conditions

Treatment Resistant Depression; Autism Spectrum Disorder

Keywords

Treatment Resistant Depression; Autism Spectrum Disorder; psilocybin-assisted therapy

Outcome Measures

Primary Outcomes (4)

• Feasibility of Administering Psilocybin in Conjunction with Psychotherapy in Autistic Adults

  Percentage of participants recruited and retained.

  From enrollment to end of treatment & follow-up at 12 weeks post-intervention (12 weeks post treatment dosing i.e., Day 0)

• Subjective Psychedelic Effects as Measured by the 11-Dimensions of Altered States of Consciousness (11D-ASC) Rating Scale

  A visual analogue scale (0-100 millimeters in length) with higher scores indicating more intense effects. Each question is attributable to one of the specified 11 dimensions of altered states of consciousness.

  Administered following each dosing session (Visit 3 (Safety dosing - Day -7)) & Visit 4 (treatment dosing - Day 0))

• Number of Participants with Treatment-Related Adverse Events as Assessed by SBQ-ASC & UKU Side Effect Rating Scale

  Treatment-Related Adverse Events are expected to be similar in nature \& frequency to those reported in previous clinical studies on classic psychedelics in neurotypical populations. The UKU Side Effect Scale will be used to capture \& document core features of any treatment-related side effects. The Suicidal Behaviors Questionnaire - Autism Spectrum Conditions (SBQ-ASC) will be used to measure suicidality in participants. It consists of 5 scored items: 1) lifetime experience of suicidal thoughts; 2) frequency of intense suicidal thoughts in the last 12 months; 3) perseverative intense suicidal thoughts; 4) likelihood of suicide attempts; 5) communication of future suicide intent \& past suicide attempts to others. The SBQ-ASC also includes optional follow-up items which are not scored, based on responses to Item 5: for those who have attempted suicide, the follow-up items address presence of plans, impulsivity, and access to means.

  From enrollment to end of treatment & follow-up at 12 weeks post-intervention (12 weeks post treatment dosing i.e., Day 0)

• Feasibility of Dense Sampling Brain MRI Procedures & Trial Design

  Percentage of participants recruited and retained for the optional dense sampling brain MRI procedures (multiple scans throughout duration of participant's involvement in study, up to 10 ).

  From enrollment to end of treatment & follow-up at 12 weeks post-intervention (12 weeks post-treatment dosing i.e., Day 0)

Secondary Outcomes (2)

• Changes in Brain Network Interactions as Assessed with Pre- and Post-Intervention MRI Brain Scans

  Evaluated using MRI before and after each dosing session (Visit 2 (Baseline Visit - Day -15 to -8)), Visit 3a (one day after safety dosing - Day -6)) & Visit 5 (one day after treatment dosing - Day 1))

• Changes & Variance in Brain Functional Connectivity Assessed Across Dense Sampling Brain MRI Sessions

  From enrollment to end of treatment & follow-up at 12 weeks post-intervention (12 weeks post treatment dosing i.e., Day 0)

Other Outcomes (2)

• Antidepressant Efficacy of Psilocybin-Assisted Psychotherapy for Autistic Adults with Treatment-Resistant Depression

  From enrollment to end of treatment & follow-up at 12 weeks post-intervention

• Changes in Psychological Symptoms & Features Theoretically Associated with Psilocybin-Assisted Psychotherapy & Depression

  Administered at follow-up visits post-intervention (Visits 5-9)

Study Arms (1)

Open-label

EXPERIMENTAL

Safety Dosing Session (V3): 10mg of psilocybin + therapy + safety evaluations Active Treatment Session (V4): 25mg of psilocybin + therapy + safety evaluations

Drug: Psilocybin

Interventions

Psilocybin DRUG

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).

Also known as: Psilocybin-Assisted Therapy

Open-label

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be aged 18 to 65 years old;
• Must be deemed to have capacity to provide informed consent;
• Ability to read and communicate in English;
• Must sign and date the informed consent form;
• Stated willingness to comply with all study procedures;
• Intellectually able: Either 1) the participant has a previous report showing intelligence quotient (IQ) ≥ 70 on the General Abilities Index of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) or any other standardized intelligence scales, or 2) the participant scores \>10 percentile on the nine-item form of the Raven's Standard Progressive Matrices Test (RSPM).
• Clinical diagnosis of autism spectrum disorder (ASD), based on the DSM-5 or ICD-11
• Primary DSM-5 diagnosis of non-psychotic MDD, single or recurrent, based on the Mini International Neuropsychiatric Interview (MINI) administered at the first screening visit (V1);
• Participants diagnosed with treatment-resistant depression defined as individuals with a baseline GRID-HAMD-17 score \> 14 and that have not responded to two or more separate trials of antidepressants at an adequate dosage and duration based on the Antidepressant Treatment History Form; there is no upper limit on the number of treatment failures;
• Ability to take oral medication;
• Individuals who are capable of becoming pregnant: use of highly effective contraception for at least 3 months prior to screening and agreement to use such a method during study participation;
• Individuals who are willing to taper off current antidepressant and antipsychotic medications for a minimum of 2-weeks (or more depending on the medication) prior to Baseline (V2) and whose physician confirms that it is safe for them to do so; and
• A clean urine drug screen and negative urine pregnancy test (in females).
• Agreement to adhere to Lifestyle Considerations (see below) throughout study duration

You may not qualify if:

• Pregnant as assessed by a urine pregnancy test or individual's that intend to become pregnant during the study or are breastfeeding;
• Treatment with another investigational drug or other intervention within 30 days of Screening (V1);
• The presence of an unstable seizure disorder as defined by having not been seizure-free for at least 6 months or anticonvulsant treatment has not been stable for at least 4 weeks;
• The presence of any clinically significant or unstable medical conditions, including cardiovascular, liver, kidney, pulmonary disease, presence of known congenital brain malformation, as per investigator assessment based on medical history and chart review;
• Moderate or severe DSM-5 diagnosis of an alcohol or substance use disorder in the past 12 months;
• Any DSM-5 lifetime diagnosis of a schizophrenia-spectrum disorder, psychotic disorder (unless substance induced or due to a medical condition), bipolar I or II disorder, paranoid personality disorder, or neurocognitive disorder as determined by medical history and the MINI clinical interview;
• Any first-degree relative with a diagnosis of schizophrenia-spectrum disorder; psychotic disorder (unless substance-induced or due to a medical condition); or bipolar I or II disorder as determined by the family medical history form and discussions with the participant;
• Presence of a relative or absolute contraindication to psilocybin, including a drug allergy, recent stroke history, uncontrolled hypertension, low or labile blood pressure, recent myocardial infarction, cardiac arrhythmic, severe coronary artery disease, or moderate to severe renal or hepatic impairment;
• Substantial lifetime use (\>10 years total) or recent use (past 6 months) of ketamine, psychedelics, or MDMA and positive urine toxicological screen at Screening (V1) and Baseline (V2);
• Any other clinically significant physical illness, including chronic infectious diseases or any other major concurrent illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if they take part in the study;
• Have active suicidal ideation with intent and plan as determined by SBQ-ASC.
• Have initiated new psychotherapy within 12 weeks prior to Screening
• Contraindication to MR imaging or a previous history of claustrophobia.
• Lifestyle considerations:
• During this clinical trial, participants are asked to:

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Autism Spectrum Disorder

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Child Development Disorders, Pervasive; Neurodevelopmental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Hsiang-Yuan Lin, MD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hsiang-Yuan Lin, MD

CONTACT

416-535-8501; Hsiang-Yuan.Lin@camh.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2024
• First Posted: December 12, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)