Psilocybin - Induced Neuroplasticity in the Treatment of Major Depressive Disorder

Phase 1

Active, not recruiting

Interventions: Drug: Low Dose Psilocybin
Drug: Placebo
Drug: Medium Dose Psilocybin

Brief Summary: 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: 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).

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo/Low Dose Psilocybin	Placebo	Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session.
Placebo/Medium Dose Psilocybin	Placebo	Subjects in this arm receive placebo in the first session and medium dose psilocybin in the second session.
Low Dose Psilocybin/Placebo	Placebo	Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session.
Medium Dose Psilocybin/Placebo	Placebo	Subjects in this arm receive medium dose psilocybin in the first session and placebo in the second session.
Placebo/Low Dose Psilocybin	Low Dose Psilocybin	Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session.
Placebo/Medium Dose Psilocybin	Medium Dose Psilocybin	Subjects in this arm receive placebo in the first session and medium dose psilocybin in the second session.
Low Dose Psilocybin/Placebo	Low Dose Psilocybin	Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session.
Medium Dose Psilocybin/Placebo	Medium Dose Psilocybin	Subjects in this arm receive medium dose psilocybin in the first session and placebo in the second session.

Primary Outcome Measures

Name	Time	Method
Changes in electrical brain activity associated with neuroplasticity measured by Electroencephalography (EEG)	One day and two weeks after each experimental session	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)

Secondary Outcome Measures

Name	Time	Method
Changes in verbal memory [ Time Frame: One day and two weeks after each experimental session ]	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.
Change in mood symptoms using the GRID-Hamilton Depression Rating Scale (GRID-HAM-D)	Four weeks before the initiation of testing, the day before and after each experimental session, and one and two weeks after each experimental session.	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.
Change in mood symptoms using the Quick Inventory of Depressive Symptoms (QIDS-SR16)	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.	The QIDS-SR16 is a 16-item self-reported rating scale designed to assess severity of depressive symptoms.

Locations (1): VA Connecticut Healthcare System, West Haven Campus
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West Haven, Connecticut, United States