Psilocybin - Induced Neuroplasticity in the Treatment of Major Depressive Disorder

NCT03554174 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 2000022394
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Disorder

Keywords

psilocybin

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Changes in verbal memory [ Time Frame: One day and two weeks after each experimental session ]

  One day and two weeks after each experimental session

• 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.

• 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.

Study Arms (4)

Placebo/Low Dose Psilocybin

EXPERIMENTAL

Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session.

Drug: Low Dose Psilocybin; Drug: Placebo

Placebo/Medium Dose Psilocybin

EXPERIMENTAL

Subjects in this arm receive placebo in the first session and medium dose psilocybin in the second session.

Drug: Placebo; Drug: Medium Dose Psilocybin

Low Dose Psilocybin/Placebo

EXPERIMENTAL

Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session.

Drug: Low Dose Psilocybin; Drug: Placebo

Medium Dose Psilocybin/Placebo

EXPERIMENTAL

Subjects in this arm receive medium dose psilocybin in the first session and placebo in the second session.

Drug: Placebo; Drug: Medium Dose Psilocybin

Interventions

Low Dose Psilocybin DRUG

0.1 mg/kg psilocybin capsule

Low Dose Psilocybin/Placebo; Placebo/Low Dose Psilocybin

Placebo DRUG

microcrystalline cellulose capsule

Low Dose Psilocybin/Placebo; Medium Dose Psilocybin/Placebo; Placebo/Low Dose Psilocybin; Placebo/Medium Dose Psilocybin

Medium Dose Psilocybin DRUG

0.3 mg/kg psilocybin capsule

Medium Dose Psilocybin/Placebo; Placebo/Medium Dose Psilocybin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• Heffter Research Institute: collaborator

Study Sites (1)

VA Connecticut Healthcare System, West Haven Campus

West Haven, Connecticut, 06516, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Deepak D'Souza, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: April 13, 2018
• First Posted: June 13, 2018
• Study Start: February 27, 2018
• Primary Completion: July 8, 2021
• Study Completion (Estimated): September 1, 2026
• Last Updated: November 5, 2025

Record last verified: 2025-11

Locations

US (1)