Psilocybin and Depression

Study Overview
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Brief Summary
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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.

Official Title
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Psilocybin and Depression - Assessing the Long-term Effects of a Single Administration of Psilocybin on the Psychiatric Symptoms and Brain Activity of Patients With Severe Depression

Conditions
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Severe Depression

Intervention / Treatment
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* Drug: Psilocybin
* Drug: Ketamine (Ketalar)


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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: In a randomized, double-blind placebo-controlled design, 20 of the participants will receive ketamine, and 20 will receive psilocybin. 20 of the participants will be included in the study as a no-treatment group, so that natural time-dependent changes in depressive symptoms can be controlled for and thus the antidepressive effects of ketamine and psilocybin treatment can be verified. The no-treatment group will only attend the initial clinical interviews, and their depressive symptoms will be assessed remotely.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Psilocybin group<br>This group will receive a single oral 25mg dose of psilocybin under surveilled and safe conditions. | Drug: Psilocybin<br>* Psilocybin ingested orally<br>|
| Active Comparator: Ketamine group<br>This group will receive a single intranasal 125mg dose of ketamine under surveilled and safe conditions. | Drug: Ketamine (Ketalar)<br>* Ketamine administered intranasally<br>|
| No Intervention: No-treatment group<br>This group will be included in the study as a no-treatment group, so that natural time-dependent changes in depressive symptoms can be controlled for and thus the antidepressive effects of ketamine and psilocybin treatment can be verified | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 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). | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fMRI, psilocybin, ketamine, biomarker, rapid-acting antidepressants