Psilocybin - Induced Neuroplasticity in the Treatment of Major Depressive Disorder

Study Overview
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Brief Summary
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The primary goal of this pilot study is to investigate whether psilocybin alters neuroplasticity in people with major depressive disorder. The primary hypothesis is that psilocybin will result in neuroplastic changes that parallel improvement in symptoms of depression.

Detailed Description
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In this placebo-controlled, blinded study, individuals with depression will participate in 2 experimental sessions approximately 4 weeks apart during which they will receive two of the following three interventions: 1) placebo, 2) low dose psilocybin (0.1 mg/kg), and 3) medium dose psilocybin (0.3 mg/kg).

Official Title
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Psilocybin - Induced Neuroplasticity in the Treatment of Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Low Dose Psilocybin
* Drug: Placebo
* Drug: Medium Dose Psilocybin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with Major Depressive Disorder (MDD), single or recurrent episode, and currently experiencing a Major Depressive Episode (MDE) Failed to achieve a satisfactory clinical response to at least one adequate antidepressant trial during the current depressive episode Currently engaged in treatment with a mental health clinician Exclusion Criteria: Axis I psychotic disorder (e.g. schizophrenia, bipolar I, depression with psychosis) Axis I psychotic disorder in first degree relative Currently taking a conventional antidepressant medication Unstable medical or neurological conditions Significant cognitive disorders History of intolerance to drugs known to significantly alter perception e.g., psilocybin, LSD, salvinorin A, mescaline, etc. Pregnant, breastfeeding, lack of adequate birth control Urine toxicology positive to drugs of abuse on experimental test days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo/Low Dose Psilocybin<br>Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session. | Drug: Low Dose Psilocybin<br>* 0.1 mg/kg psilocybin capsule<br>Drug: Placebo<br>* microcrystalline cellulose capsule<br>|
| Experimental: Placebo/Medium Dose Psilocybin<br>Subjects in this arm receive placebo in the first session and medium dose psilocybin in the second session. | Drug: Placebo<br>* microcrystalline cellulose capsule<br>Drug: Medium Dose Psilocybin<br>* 0.3 mg/kg psilocybin capsule<br>|
| Experimental: Low Dose Psilocybin/Placebo<br>Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session. | Drug: Low Dose Psilocybin<br>* 0.1 mg/kg psilocybin capsule<br>Drug: Placebo<br>* microcrystalline cellulose capsule<br>|
| Experimental: Medium Dose Psilocybin/Placebo<br>Subjects in this arm receive medium dose psilocybin in the first session and placebo in the second session. | Drug: Placebo<br>* microcrystalline cellulose capsule<br>Drug: Medium Dose Psilocybin<br>* 0.3 mg/kg psilocybin capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in electrical brain activity associated with neuroplasticity measured by Electroencephalography (EEG) | An auditory Long Term Potentiation (LTP) task will assess changes in neuroplasticity. For the EEG task, the outcome measures will include stimulus-evoked time x frequency analysis (e.g., spectral power) | One day and two weeks after each experimental session | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in verbal memory [ Time Frame: One day and two weeks after each experimental session ] | This will be measured by a modified computer version of the Rey Auditory Verbal Learning Test (RAVLT), administered while EEG data is collected. The EEG outcomes will include time x frequency analysis (e.g., spectral power) during the learning and recognition phases of the task. | One day and two weeks after each experimental session | 
| Change in mood symptoms using the GRID-Hamilton Depression Rating Scale (GRID-HAM-D) | The GRID-Hamilton Depression Rating Scale is a clinician-administered rating scale designed to assess severity of depressive symptoms. It includes 17 items, nine of which are scored on 5-point scale, and eight of which are scored on a three-point scale. The score range for the GRID-HAMD is 0 to 52, with higher score indicating more severe depression. | Four weeks before the initiation of testing, the day before and after each experimental session, and one and two weeks after each experimental session. | 
| Change in mood symptoms using the Quick Inventory of Depressive Symptoms (QIDS-SR16) | The QIDS-SR16 is a 16-item self-reported rating scale designed to assess severity of depressive symptoms. | Four weeks before the initiation of testing, the day before and after each experimental session, one and two weeks after each experimental session, then monthly for three months after the last experimental session. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psilocybin