Psilocybin - Induced Neuroplasticity in the Treatment of Major Depressive Disorder

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Low Dose Psilocybin; Drug: Medium Dose Psilocybin

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).

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • VA Connecticut Healthcare System, West Haven Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Heffter Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2018
• Primary Completion (Estimated): February 27, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: April 13, 2018
• First Submitted That Met QC Criteria: June 5, 2018
• First Posted (Actual): June 13, 2018

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: June 5, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: psilocybin
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Psychotropic Drugs; Hallucinogens; Psilocybin
• Other Study ID Numbers: 2000022394

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No