Major Depressive DisorderPhase 1NCT03554174
Psilocybin - Induced Neuroplasticity in the Treatment of Major Depressive Disorder
A Phase 1 study testing Low Dose Psilocybin and Medium Dose Psilocybin in people with Major Depressive Disorder, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Low Dose Psilocybin and Medium Dose Psilocybin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Feb 2018to Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Connecticut Healthcare System, West Haven Campus
West Haven, Connecticut, 06516
About this study
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.
Read the 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).
- Conditions
- Major Depressive Disorder
- Being tested
- Low Dose Psilocybin, Placebo, Medium Dose Psilocybin
- Keywords
- psilocybin
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Dose PsilocybinDrug
0.1 mg/kg psilocybin capsule
PlaceboDrug
microcrystalline cellulose capsule
Medium Dose PsilocybinDrug
0.3 mg/kg psilocybin capsule
| Study group | Role | What they receive |
|---|---|---|
| Placebo/Low Dose Psilocybin | Experimental | Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Placebo; Drug: Medium Dose Psilocybin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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 ]
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.
Measured: 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.
Measured: 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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2018
- Study start27 Feb 2018
- Primary completion8 Jul 2021
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Heffter Research Institute
- Responsible party
- Principal investigator, Deepak C. D'Souza, Yale University
- Investigators
- Deepak D'Souza, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03554174
- Sponsor's protocol ID
- 2000022394
- Status last verified
- Nov 2026
- First submitted
- 13 Apr 2018
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Psilocybin - Induced Neuroplasticity in the Treatment of Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT03554174
- Acronym / sponsor ID
- 2000022394
- Conditions
- Major Depressive Disorder
- Keywords
- psilocybin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Heffter Research Institute
- Study start
- 27 Feb 2018 (actual)
- Primary completion
- 8 Jul 2021 (actual)
- Study completion
- Dec 2026 (estimated)
- First posted
- 13 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, care provider)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo/Low Dose Psilocybin | Experimental | Drug: Low Dose Psilocybin, Drug: PlaceboSubjects in this arm receive placebo in the first session and low dose psilocybin in the second session. |
| Placebo/Medium Dose Psilocybin | Experimental | Drug: Placebo, Drug: Medium Dose PsilocybinSubjects in this arm receive placebo in the first session and medium dose psilocybin in the second session. |
| Low Dose Psilocybin/Placebo | Experimental | Drug: Low Dose Psilocybin, Drug: PlaceboSubjects in this arm receive low dose psilocybin in the first session and placebo in the second session. |
| Medium Dose Psilocybin/Placebo | Experimental | Drug: Placebo, Drug: Medium Dose PsilocybinSubjects in this arm receive medium dose psilocybin in the first session and placebo in the second session. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low Dose Psilocybin0.1 mg/kg psilocybin capsule | Drug | Low Dose Psilocybin/Placebo, Placebo/Low Dose Psilocybin |
| Placebomicrocrystalline cellulose capsule | Drug | Low Dose Psilocybin/Placebo, Medium Dose Psilocybin/Placebo, Placebo/Low Dose Psilocybin, Placebo/Medium Dose Psilocybin |
| Medium Dose Psilocybin0.3 mg/kg psilocybin capsule | Drug | Medium Dose Psilocybin/Placebo, Placebo/Medium Dose Psilocybin |
Primary outcome
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)
3 secondary outcomes
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
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.
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
Related trials for Major Depressive Disorder
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deepak D'Souza, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Low Dose Psilocybin and Medium Dose Psilocybin in people with Major Depressive Disorder, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in electrical brain activity associated with neuroplasticity measured by Electroencephalography (EEG) (time frame: One day and two weeks after each experimental session). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.