Clinical TrialMajor Depressive Disorder (MDD)PsilocybinPlaceboPsilocybinRecruiting

A Randomized Neuroimaging Trial of Psilocybin in Depression

Randomised Phase II neuroimaging crossover trial (n=50) testing oral psilocybin 25 mg versus microcrystalline cellulose placebo in participants with depressive disorder; two treatment sessions with MRI assessments and supportive psychotherapy.

Target Enrollment
50 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind

Detailed Description

This randomised, two-group delayed-start (AB/BB) crossover neuroimaging trial will compare brain activity after psilocybin 25 mg versus placebo (microcrystalline cellulose 25 mg) across two treatment sessions in patients with depressive disorder.

Participants undergo MRI after drug administration and prior to supportive psychotherapy at each session; primary outcomes assess changes in connectivity and regional blood flow in mood-related networks.

An interim analysis is planned after 20 participants to evaluate preliminary efficacy and safety; all participants receive supportive psychotherapy and clinical follow-up arrangements are required.

Study Protocol

Preparation

sessions

Dosing

2 sessions

Integration

sessions

Therapeutic Protocol

support

Study Arms & Interventions

Psilocybin–Psilocybin

experimental

Staged active treatment arm receiving psilocybin 25 mg at both treatment visits with supportive psychotherapy.

Interventions

  • Psilocybin25 mg
    via Oral• single dose• 2 doses total

    Psilocybin 25 mg at each of two sessions; supportive psychotherapy provided at each session.

  • Compound

    Supportive psychotherapy (reassurance, integration, de-escalation) at each visit.

MCC–Psilocybin (Delayed start)

experimental

Placebo (microcrystalline cellulose 25 mg) at first visit then psilocybin 25 mg at second visit; supportive psychotherapy at both visits.

Interventions

  • Placebo25 mg
    via Oral• single dose• 1 doses total

    Microcrystalline cellulose (MCC) 25 mg at first visit (placebo).

  • Psilocybin25 mg
    via Oral• single dose• 1 doses total

    Psilocybin 25 mg at second visit.

  • Compound

    Supportive psychotherapy (reassurance, integration, de-escalation) at each visit.

Participants

Ages
18 – 64
Sexes
Male & Female

Inclusion Criteria

  • 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

  • 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

Study Details

Locations

Sunnybrook Health Sciences Centre — Toronto, Ontario, Canada

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