A Randomized Neuroimaging Trial of Psilocybin in Depression

Launched by SUNNYBROOK HEALTH SCIENCES CENTRE · Oct 2, 2023

Keywords

ClinConnect Summary

This clinical trial is studying how a substance called psilocybin, found in certain mushrooms, affects the brain activity of people with major depressive disorder. Researchers want to see if psilocybin can change how different parts of the brain communicate with each other and how blood flows in areas linked to mood and depression. Participants will take part in two treatment sessions where they will receive either psilocybin or a placebo, along with supportive therapy. After taking the medication, participants will have an MRI scan to observe any changes in their brain activity.

To participate, individuals must be between 18 and 65 years old and have a confirmed diagnosis of depression that has lasted for at least three months. They should also have a reliable caregiver to monitor them after treatment and be able to attend all study visits. However, certain medical conditions, such as a history of seizures or uncontrolled diabetes, may exclude individuals from the trial. This study is currently recruiting participants, and those who join can expect a supportive environment where their mental health is prioritized throughout the process.

Gender

ALL

Eligibility 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:
• • 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