Psilocybin for Treatment-Resistant Depression in Autism
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-65
SponsorCentre for Addiction and Mental Health
About this trial
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)
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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;
Disqualifiers
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;
Trial design
Design model
Single group
Treatments tested in this trial
Psilocybin
Drug2 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).
Treatment groups
20 Participants
are divided into 1 treatment groupGroup A: Open-labelExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Feasibility of Administering Psilocybin in Conjunction with Psychotherapy in Autistic Adults
Percentage of participants recruited and retained.
Time frame
From enrollment to end of treatment & follow-up at 12 weeks post-intervention (12 weeks post treatment dosing i.e., Day 0)2
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.
Time frame
Administered following each dosing session (Visit 3 (Safety dosing - Day -7)) & Visit 4 (treatment dosing - Day 0))3
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.
Time frame
From enrollment to end of treatment & follow-up at 12 weeks post-intervention (12 weeks post treatment dosing i.e., Day 0)4
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 ).
Time frame
From enrollment to end of treatment & follow-up at 12 weeks post-intervention (12 weeks post-treatment dosing i.e., Day 0)Secondary outcomes
1
Changes in Brain Network Interactions as Assessed with Pre- and Post-Intervention MRI Brain Scans
Brain MRI scans and subsequent brain network \& cognitive modelling will be used to assess \& study changes in brain network interactions and possible mechanisms underpinning antidepressant effects of psilocybin for treatment-resistant depression in autism.
Time frame
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))2
Changes & Variance in Brain Functional Connectivity Assessed Across Dense Sampling Brain MRI Sessions
The optional dense sampling brain MRI procedures will allow for a more robust model of the brain and changes/variance that may be observed in an individual's brain over the course of the study, particularly in response to the intervention. Brain MRI scans and subsequent brain network \& cognitive modelling will be used to assess \& study changes in brain network interactions and possible mechanisms underpinning antidepressant effects of psilocybin for treatment-resistant depression in autism.
Time frame
From enrollment to end of treatment & follow-up at 12 weeks post-intervention (12 weeks post treatment dosing i.e., Day 0)Other outcomes
1
Antidepressant Efficacy of Psilocybin-Assisted Psychotherapy for Autistic Adults with Treatment-Resistant Depression
The following measures will assess antidepressant efficacy: Clinical Global Impression Scale (CGI) - Clinician-administered scale providing a brief, stand-alone assessment of the clinician's view of the participant's global functioning before and after initiating study medication. 7-point scale; higher scores indicate more severe symptoms. Beck Depression Inventory II (BDI-II) - 4-point scale measuring severity of depression and related symptoms; higher scores indicate more severe depressive symptoms. Snaith-Hamilton Pleasure Scale (SHAPS) - 4-point scale measuring hedonic capacity; lower scores indicate greater hedonic capacity (less anhedonia). Ruminative Responses Scale (RRS-10) - 4-point scale describing responses to depressed mood; higher scores reflect more severe rumination. Anxiety Scale for Autism - Adults (ASA-A) - 4-point scale measuring anxiety in autistic adults; higher scores indicate greater anxiety.
Time frame
From enrollment to end of treatment & follow-up at 12 weeks post-intervention2
Changes in Psychological Symptoms & Features Theoretically Associated with Psilocybin-Assisted Psychotherapy & Depression
General Alexithymia Factor Score (GAFS-8) - Self-report assessing difficulty identifying and describing feelings. Acceptance \& Action Questionnaire-II (AAQ-II) - Self-report measuring experiential avoidance and psychological inflexibility. Autism Burnout Survey Items (ABSI) - Self-report quantifying autistic burnout (exhaustion, withdrawal, cognitive overload) from stressors amplified in autistic individuals. Connor-Davidson Resilience Scale 10 (CD-RISC-10) - Measures resilience and flexibility in adapting to stressful situations. Interoception Sensory Questionnaire-8 (ISQ-8) - Measures perception and interpretation of interoceptive capacity. Interpersonal Needs Questionnaire (INQ-15) - Assesses 'thwarted belongingness' and 'perceived burdensomeness'. Cognitive Flexibility Inventory (CFI) - Self-report assessing cognitive flexibility in challenging and replacing maladaptive thoughts.
Time frame
Administered at follow-up visits post-intervention (Visits 5-9)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov