A Phase 1 interventional study of Low Dose Psilocybin and Placebo in Major Depressive Disorder, sponsored by Yale University. Active, not recruiting at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2025-11-05.
Sponsored by Yale University · Phase 1, Interventional, and Treatment
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.
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).
2,741 studies on the registry are indexed under Depressive Disorder, Major; 559 are open to participants now.
This study's planned enrollment of 18 is below the median of 80 across 2,283 interventional studies indexed under Depressive Disorder, Major.
Browse Depressive Disorder, Major studies →Yale University is the lead sponsor of 1,724 studies on the registry; 298 are open to participants now.
Of its 210 completed or terminated interventional studies of FDA-regulated products, 126 (60%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session.
Drug: Low Dose Psilocybin · Drug: Placebo
Subjects in this arm receive placebo in the first session and medium dose psilocybin in the second session.
Drug: Placebo · Drug: Medium Dose Psilocybin
Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session.
Drug: Low Dose Psilocybin · Drug: Placebo
Subjects in this arm receive medium dose psilocybin in the first session and placebo in the second session.
Drug: Placebo · Drug: Medium Dose Psilocybin
0.1 mg/kg psilocybin capsule
microcrystalline cellulose capsule
0.3 mg/kg psilocybin capsule
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)
Time frame: One day and two weeks after each experimental session
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.
Time frame: 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.
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.
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.
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.
This study is active, not recruiting, as verified in Nov 2025. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Yale University