A Randomized Neuroimaging Trial of Psilocybin in Depression (EMBRACE)

Sunnybrook Health Sciences Centre

Status and phase: Enrolling; Phase 2

Conditions: Major Depressive Disorder; Depressive Disorder

Treatments: Behavioral: Supportive psychotherapy; Drug: Psilocybin; Other: Microcrystalline cellulose

Study type: Interventional

Funder types: Other

Identifiers

NCT06072898

5423

Details and patient eligibility

About

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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Able and voluntarily willing to provide written informed consent at the screening visit.
• Over 18 and under 65 years old
• Able to attend all study visits and complete all required assessment tools without assistance or alteration
• Have a responsible individual/caregiver who is able to monitor the participant at home for 24 hours after each treatment visit
• Must have a psychiatrist and/or general practitioner who is able to provide psychiatric follow-up care
• Mini International Neuropsychiatric Interview (MINI)-confirmed diagnosis of depressive disorder, recurrent or single episode, without psychotic features where the duration of the current episode is at least 3 months
• Depression of at least moderate severity as defined by a Hamilton Depression Rating Scale (HAMD-17) score >17

Exclusion criteria

• Uncontrolled or insulin-dependent diabetes
• Women who are pregnant (self-report or via urine test), nursing, or planning a pregnancy during the timespan of the study
• History of seizure disorder except for seizures from electroconvulsive therapy and/or febrile seizures in childhood
• History of stroke, recent myocardial infarction (< 1 year from signing of ICF), uncontrolled hypertension (blood pressure > 140/90 mmHg) or clinically significant arrhythmia within 1 year of signing the ICF
• Abnormal and clinically significant results on a physical examination performed within one month of study participation by a general practitioner, vital signs, ECG, or laboratory test at screening
• QTc prolongation on ECG defined by > 450 ms in males and > 460 ms in females in V5 on a 12-lead ECG
• Positive urine drug screen for illicit drugs or drugs of abuse at screening, a week prior to treatment, and during the trial (any positive urine drug test will be reviewed with participants to determine the pattern of use and eligibility will be determined at the investigator's discretion)
• Serial blood counts to achieve a value to meet eligibility -- abnormalities in screening/baseline blood work (complete blood counts, electrolyte panel, etc.) will be reviewed by MD, then repeated serially until abnormalities resolve
• Any symptoms consistent with psychosis
• Any symptoms consistent with hypomania and/or mania as assessed by a psychiatrist
• Other personal circumstances or behavior judged to be incompatible with establishment of rapport or safe exposure to psilocybin
• 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)
• ≥ 1 suicide attempt in the past year requiring hospitalization, defined using the Columbia Suicide Severity Rating Scale (CSSRS) (Q6 (past year) = "y") and clinical interview with a psychiatrist
• History of substance use and/or alcohol use disorder, of moderate severity or greater, in the past 12 months
• Lifetime history of substance use disorder with a hallucinogen
• Lifetime history of substance-induced psychosis
• Depression secondary to other medical conditions or bipolar I and II disorder
• Family history of a first degree relative with a diagnosis of schizophrenia or a primary psychotic disorder and/or bipolar disorder
• Exposure to psilocybin or any other psychedelic in the past 12 months prior to screening and/or during the current MDE and use of psychedelics, such as ayahuasca/LSD, during the current depressive episode
• A clinical diagnosis of antisocial personality disorder and/or paranoid personality disorder (defined as meeting DSM-5.0 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
• Diagnosis of any mild or major neurocognitive disorder meeting DSM-5 criteria and based on clinical interview/cognitive screening by a psychiatrist
• Current enrolment in an interventional study for depression or participation in such within 30 days of screening
• Any other clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal 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 he/she takes part in the study

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

---

50 participants in 2 patient groups

Staged Active Treatment Arm (Psilocybin-Psilocybin)

Experimental group

Description:

This group will receive psilocybin (25mg) at the first and second treatment visit, along with supportive psychotherapy.

Treatment:

Drug: Psilocybin

Behavioral: Supportive psychotherapy

Placebo to Active Delayed-Start Treatment Arm (MCC-Psilocybin)

Experimental group

Description:

This group will receive microcrystalline cellulose (25mg) at the first treatment visit and psilocybin (25mg) at the second treatment visit, along with supportive psychotherapy.

Treatment:

Other: Microcrystalline cellulose

Drug: Psilocybin

Behavioral: Supportive psychotherapy