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Active, Not Recruiting

NCT Number: NCT03554174

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Major Depressive Disorder Depressive Disorder Depressive Disorder, Major Mental Disorders Mood Disorders

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

VA Connecticut Healthcare System, West Haven Campus

West Haven, Connecticut, 06516, United States

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Low Dose Psilocybin

Drug

0.1 mg/kg psilocybin capsule

Placebo

Drug

microcrystalline cellulose capsule

Medium Dose Psilocybin

Drug

0.3 mg/kg psilocybin capsule

Primary outcomes

  1. Changes in electrical brain activity associated with neuroplasticity measured by Electroencephalography (EEG)

    Time frame: 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 outcomes

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

    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.

  2. Change in mood symptoms using the GRID-Hamilton Depression Rating Scale (GRID-HAM-D)

    Time frame: 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)

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Yale University

Other

Collaborators

  • Heffter Research Institute

Registry information

Important dates

Study start
2018
Primary completion
2021
Study completion
2026
First posted
Jun 13, 2018
Registry last updated
Nov 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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