Psilocybin and Depression

University of Helsinki60 enrolled

Overview

The main aim of the study is to investigate the possible long-term therapeutic effects of psilocybin on the symptoms of severe depression, as well as the brain mechanisms underlying these changes. Depression severity is assessed before and after (i.e., 1 week, 3 months and 6 months after) a single dose of psilocybin and compared to respective scores of a group receiving an active placebo, ketamine. Brain activity (using functional magnetic resonance imaging) is measured before and one week after drug administration in order to determine whether changes in brain networks related to emotional and self-referential processing correlate with any observed changes in depression scores. Further, blood samples will be obtained from the participants and analyzed in order to reveal gene expression and molecular level correlates underlying rapid antidepressant effects, and to identify biomarkers that predict treatment outcome.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Enrollment

Conditions

Severe Depression

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 64 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Major depression of a moderate to severe degree (17+ on the 21-item HAM-D). 2. No health-related contraindications. Exclusion Criteria: 1. Current or previously diagnosed psychotic disorder. 2. Immediate family member with a diagnosed psychotic disorder. 3. Medically significant condition rendering unsuitability for the study (e.g., diabetes, epilepsy, severe cardiovascular disease, hepatic or renal failure etc.). 4. History of suicide attempts. 5. History of mania. 6. Current 5-HT2A antagonist antidepressant medication. 7. Blood or needle phobia. 8. Positive pregnancy test. 9. Current drug or alcohol dependence. 10. Lack of appropriate use of contraception. 11. Breast-feeding.

Outcomes

Primary Outcomes

The 16-Item Quick Inventory of Depressive Symptomatology (QIDS)

The primary outcome measures in this study will be the mean change in QIDS scores from pre-administration baseline at day 1 to Follow-up 2 at day 103 (3 months after the administration session). Additionally, an electronic version of the QIDS will be performed 6 months after the administration session. The criteria for determining response will be a reduction of 25% in the (QIDS; Rush et al., 2003) scores from baseline (screening), and remission will be scores of ≤5 on the QIDS.

Time frame: 6 months

Secondary Outcomes

The Montgomery and Asberg Depression Rating Scale

The Montgomery and Asberg Depression Rating Scale will be carried out at screening ( day 1), Follow-up 1 (day 18) and Follow-up 2 (day 103, 3 months after the administration session).

Time frame: 3 months

Hamilton Depression Rating Scale

The Hamilton Depression Rating Scale will be carried out at screening ( day 1), Follow-up 1 (day 18) and Follow-up 2 (day 103, 3 months after the administration session).