A Randomized Neuroimaging Trial of Psilocybin in Depression
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-64
SponsorSunnybrook Health Sciences Centre
About this trial
The goal of this neuroimaging clinical trial is to test whether psilocybin produces significant immediate changes in functional brain activity in networks associated with mood regulation and depression compared to placebo in patients with depression. The trial aims to determine if psilocybin:
1. Changes connectivity within brain networks associated with mood and depression 2. Changes blood flow in brain regions associated with mood and depression
Participants will be attend two treatment sessions where they receive an oral medication and supportive psychotherapy. At each session, participants will undergo an MRI scan after drug administration but prior to psychotherapy. Participants will be randomly to assigned to one of two groups that will receive, 1) microcrystalline cellulose (25mg) at the first visit and psilocybin (25mg) at the second visit, or 2) psilocybin (25mg) at both visits, respectively. Differences between groups will be compared to understand what effects on brain activity are specific to psilocybin.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Able and voluntarily willing to provide written informed consent at the screening visit
Over 18 and under 65 years old
Able to complete all protocol required assessment tools without any assistance or alteration to the copyrighted assessments, and to comply with all study visits
Must have a responsible individual/caregiver who is able to monitor the participant at home for 24 hours after each treatment visit in the study
Disqualifiers
Current or past history of bipolar I/II disorder, schizophrenia, schizoaffective disorder, psychotic disorder, or delusional disorder as assessed by a structured clinical interview (MINI)
A clinical diagnosis of antisocial personality disorder and/or paranoid personality disorder (defined as meeting DSM-5 criteria) based on clinical interview and the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at a clinical interview by a psychiatrist.
An active clinical diagnosis of borderline personality disorder as confirmed by the MINI 7.0.
Depression secondary to other medical conditions or bipolar I and II disorder
Trial design
Design model
Crossover
Treatments tested in this trial
Psilocybin
DrugPsilocybin (\[3-\[2-(dimethylamino)ethyl\]-1H-indol-4-yl\] dihydrogen phosphate), 25mg PO.
Microcrystalline cellulose
Other interventionMCC (excipient), 25mg PO.
Supportive psychotherapy
BehavioralSupportive psychotherapy in the form of reassurance, integration, and de-escalatory techniques (if needed). Facilitating rapport and a positive environment.
Treatment groups
50 Participants
are divided into 2 treatment groupsGroup A: Staged Active Treatment Arm (Psilocybin-Psilocybin)Experimental treatment 2 interventions
Group B: Placebo to Active Delayed-Start Treatment Arm (MCC-Psilocybin)Experimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Regional Cerebral Blood Flow
Changes in cerebral blood flow within three a priori-defined brain regions relevant to mood regulation and depression as assessed by arterial spin labeling acutely at expected peak drug concentration during treatment visits.
Time frame
Up to 3 weeks2
Montgomery-Asberg Depression Rating Scale (MADRS) Changes
Changes in the MADRS relative to baseline at study follow-up visits. Higher scores with respect to the MADRS minimum (0) and maximum (60) values represent a worse treatment outcome .
Time frame
Up to 6 weeksSecondary outcomes
1
Functional Network Connectivity
Changes in voxel-wise functional connectivity within four a priori-defined and established functional networks relevant to mood regulation and depression as assessed by resting state functional magnetic resonance imaging acutely at the time of expected peak drug concentration during treatment visits.
Time frame
Up to 3 weeks2
17-item Hamilton Depression Rating Scale (GRID-HAMD-17)
Baseline grid-version of the 17-item Hamilton Depression Rating Scale score. The GRID-HAMD is a 17-item clinician-administered rating scale designed to assess severity of depressive symptoms. The score range is 0 to 52, with higher score indicating more severe depression .
Time frame
24 hours3
Incidence of response
Incidence of response, calculated as the proportion of participants with a response (defined as a ≥ 50% improvement in MADRS total score from Baseline) at at follow-up after psilocybin administration.
Time frame
up to 6 weeks4
Incidence of remission
Incidence of remission, calculated as the proportion of participants with remission (defined as MADRS total score \<11) at week 3 and 6 following the initial psilocybin/niacin administration.
Time frame
up to 6 weeksOther outcomes
1
Blood biomarkers
Correlation of blood for circulating biomarkers will occur at baseline. Plasma-derived proteins (brain-derived neurotrophic factor, S100Beta, C-reactive protein) will be measured in blood samples collected at the baseline visit and second treatment visit using fluorometric immunoassays and evaluated as predictors of subsequent treatment response as defined above based on MADRS scores.
Time frame
up to 5 weeksSponsors and contacts
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Source ClinicalTrials.gov