Psilocybin - Induced Neuroplasticity in the Treatment of Major Depressive Disorder

• Sponsor: Yale University (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03554174
• Collaborator: Heffter Research Institute (Other)
• Enrollment: 18
• Location: 1
• Arms: 4
• Anticipated Duration (Months): 61.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Low Dose Psilocybin; Drug: Placebo; Drug: Medium Dose Psilocybin	Phase 1

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: Psilocybin - Induced Neuroplasticity in the Treatment of Major Depressive Disorder
• Actual Study Start Date: Feb 27, 2018
• Anticipated Primary Completion Date: Feb 27, 2023
• Anticipated Study Completion Date: Apr 1, 2023

Arms and Interventions

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: Low Dose Psilocybin; 0.1 mg/kg psilocybin capsule; Drug: Placebo; microcrystalline cellulose 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: Low Dose Psilocybin/Placebo Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session.	Drug: Low Dose Psilocybin; 0.1 mg/kg psilocybin capsule; Drug: Placebo; microcrystalline cellulose 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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Connecticut Healthcare System, West Haven Campus	West Haven	Connecticut	United States	06516

Sponsors and Collaborators

• Yale University
• Heffter Research Institute

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Deepak C. D'Souza, Professor of Psychiatry, Yale University
• ClinicalTrials.gov Identifier: NCT03554174
• Other Study ID Numbers: 2000022394
• First Posted: Jun 13, 2018
• Last Update Posted: Jul 20, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Deepak C. D'Souza, Professor of Psychiatry, Yale University: psilocybin
• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Psilocybin

Study Results

No Results Posted as of Jul 20, 2022