Depressive SymptomsEarly Phase 1NCT04123314
Psilocybin for Depression in People With Mild Cognitive Impairment or Early Alzheimer's Disease
A Early Phase 1 study testing Psilocybin in people with Depressive Symptoms and Depression, run by Johns Hopkins University at 1 site in United States.
Trial summary
This open-label pilot study examines whether the hallucinogenic drug, psilocybin, given under supportive conditions, is safe and effective for depression in people with Mild Cognitive Impairment (MCI) or early Alzheimer's Disease (AD). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Depressive Symptoms, Depression, Alzheimer Disease
- What is being tested?
- Psilocybin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Mar 2021to 30 Sep 2027
- Phase
- Early 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must meet either A) Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) criteria for Mild Neurocognitive Disorder due to AD or Major Neurocognitive Disorder due to AD with Mild severity (including probable), or B) meet criteria for MCI including a subjective memory complaint relative to previous functioning and confirmed by Clinical Dementia Rating (CDR) Memory score at screening of >0.5
- Have Mini-Mental State Examination scores >18
- Have a Montreal Cognitive Assessment score <26.
- Have Cornell Scale for Depression in Dementia (CSDD) patient score >/= 6, or Geriatric Depression Scale-Short Form score ≥ 5, indicating at minimum a mild to moderate degree of distress.
- Acetylcholinesterase inhibitors are allowed so long as the dose has been stable for > 6 weeks.
- Concurrent pharmacotherapy with selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRI), and/or bupropion is allowed if the type and frequency of the therapy has been stable for at least two months prior to screening. Allowable bupropion doses for participants will be ≤300mg/day.
- Have a close friend or family member willing and able to serve the role of community observer / informant for data collection procedures
Who cannot join
- Individuals 86 years of age or older will be excluded.
- Currently taking antipsychotics, monoamine oxidase (MAO) inhibitors, or antidepressant medications other than SSRIs, SNRIs, or bupropion. Allowable bupropion doses for participants will be ≤300mg/day.
- Long-acting opioid pain medications (e.g. oxycodone sustained release, morphine sustained release - which are usually taken at 12 hour intervals) will be allowed if the last dose occurred at least 2 hours before psilocybin administration and the next dose was not scheduled until at least 8 hours after psilocybin administration.
- Participants must agree not to take sildenafil, tadalafil, or similar medications within 72 hours of each psilocybin administration, as these medications may potentiate hypotensive reactions to psilocybin
- Cardiovascular conditions: angina, a clinically significant ECG abnormality (e.g. atrial fibrillation or heart-rate corrected QT interval (QTc) >450msec), Transient Ischemic Attack (TIA) in the last 6 months, stroke, artificial heart valves, or uncontrolled hypertension with resting blood pressure systolic >150 or diastolic >95
- Minimum acceptable heartrate at screening is 50 bpm unless the individual is cleared for participation by a cardiologist, in accord with the American College of Cardiology's 2018 guidelines for bradycardia
Show all 13Show fewer
- Seizure disorder
- Insulin dependent diabetes mellitus
- Renal disease (creatinine clearance < 40 ml/min using the Cockcroft and Gault equation)
- Baseline liver enzyme elevation >2x the upper limit of normal
- Current or past history of meeting DSM-5 criteria for Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I Disorder
- Family (i.e., 1st degree relative) history of Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I Disorder
- Past-year hallucinogen use.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Johns Hopkins Center for Psychedelic and Consciousness Research
Baltimore, Maryland, 21224
Ian Geithner, MPS, 410-550-5466, igeithn1@jhmi.edu
Albert Garcia-Romeu, PhD, 410-550-1972, agarci33@jhmi.edu
About this study
Official title: Pilot Study of Serotonin 2A Receptor (5-HT2A) Agonist Psilocybin for Depression in Patients With Mild Cognitive Impairment or Early Alzheimer's Disease
This open-label pilot study examines whether the hallucinogenic drug, psilocybin, given under supportive conditions, is safe and effective for depression in people with Mild Cognitive Impairment (MCI) or early Alzheimer's Disease (AD). This study will also assess whether psilocybin may improve quality of life in those individuals.
Read the detailed description
This is a pilot study evaluating the potential efficacy of psilocybin to produce improvement in depression compared to pre-treatment in people with Mild Cognitive Impairment (MCI) or early Alzheimer's Disease (AD) and clinically significant symptoms of depression. The study will be an open-label trial in a sample of up to 20 treatment-seeking participants with a diagnosis of MCI or early AD. Participants will complete an 8-week course of study treatment including two psilocybin sessions (15 mg/70 kg in week 4 and 15 or 25 mg/70 kg in week 6), with follow-up assessments up to 6 months after the final psilocybin session. The study will assess changes in depressed mood at 1 week after the second psilocybin session compared to pre-treatment, and quality of life in participants from pre- to post-treatment.
- Being tested
- Psilocybin
- Keywords
- Psilocybin, Hallucinogen, Psychedelic
- Medical subject headings
- Depression, Alzheimer Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PsilocybinDrug
Dosing at the first session will be 15 mg/70 kg. For the second session participants will either remain at the initial dose, or increase to 25 mg/70 kg at the discretion of the study team.
| Study group | Role | What they receive |
|---|---|---|
| Psilocybin | Experimental | Participants will complete an 8-week course of study treatment including weekly psychological support and two moderate to high dose psilocybin administrations in weeks 4 and 6. Receives: Drug: Psilocybin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cornell Scale for Depression in Dementia (CSDD) score
The Cornell Scale for Depression in Dementia (CSDD) is administered via patient and informant interviews to assess the presence and severity of depressive mood and behavioral symptoms during the past week. Has 19 items, each scored from 0 to 2 with higher scores indicating severe symptom.Total score range from 0 to 38.
Measured: Baseline and 1 week after second psilocybin session
Secondary outcomes (1)
Change in Quality of Life Alzheimer's Disease (QOL-AD) scale score
The Quality of Life Alzheimer's Disease (QOL-AD) scale is a 13-item measure administered via patient and informant interviews to assess overall mood, physical and cognitive function, and quality of relationships in people with Alzheimer's Disease. Each item is scored 1 to 4, with higher score indicating better quality of life. Total score range from 13 to 52.
Measured: Baseline and 2 weeks after second psilocybin session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2019
- Study start24 Mar 2021
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Depressive SymptomsStudies of the same condition, open and under way.
- More trials run by Johns Hopkins 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- Council On Spiritual Practices, Heffter Research Institute
- Responsible party
- Sponsor
- Investigators
- Albert Garcia-Romeu, PhD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04123314
- Sponsor's protocol ID
- IRB00175915
- Status last verified
- Sep 2026
- First submitted
- 9 Oct 2019
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Serotonin 2A Receptor (5-HT2A) Agonist Psilocybin for Depression in Patients With Mild Cognitive Impairment or Early Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT04123314
- Acronym / sponsor ID
- IRB00175915
- Keywords
- Psilocybin, Hallucinogen, Psychedelic
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- Council On Spiritual Practices, Heffter Research Institute
- Study start
- 24 Mar 2021 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 10 Oct 2019 (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.
This open-label pilot study examines whether the hallucinogenic drug, psilocybin, given under supportive conditions, is safe and effective for depression in people with Mild Cognitive Impairment (MCI) or early Alzheimer's Disease (AD). This study will also assess whether psilocybin may improve quality of life in those individuals.
Detailed description
This is a pilot study evaluating the potential efficacy of psilocybin to produce improvement in depression compared to pre-treatment in people with Mild Cognitive Impairment (MCI) or early Alzheimer's Disease (AD) and clinically significant symptoms of depression. The study will be an open-label trial in a sample of up to 20 treatment-seeking participants with a diagnosis of MCI or early AD. Participants will complete an 8-week course of study treatment including two psilocybin sessions (15 mg/70 kg in week 4 and 15 or 25 mg/70 kg in week 6), with follow-up assessments up to 6 months after the final psilocybin session. The study will assess changes in depressed mood at 1 week after the second psilocybin session compared to pre-treatment, and quality of life in participants from pre- to post-treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Psilocybin | Experimental | Drug: PsilocybinParticipants will complete an 8-week course of study treatment including weekly psychological support and two moderate to high dose psilocybin administrations in weeks 4 and 6. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Must meet either A) Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) criteria for Mild Neurocognitive Disorder due to AD or Major Neurocognitive Disorder due to AD with Mild severity (including probable), or B) meet criteria for MCI including a subjective memory complaint relative to previous functioning and confirmed by Clinical Dementia Rating (CDR) Memory score at screening of >0.5
- Have Mini-Mental State Examination scores >18
- Have a Montreal Cognitive Assessment score <26.
- Have Cornell Scale for Depression in Dementia (CSDD) patient score >/= 6, or Geriatric Depression Scale-Short Form score ≥ 5, indicating at minimum a mild to moderate degree of distress.
- Acetylcholinesterase inhibitors are allowed so long as the dose has been stable for > 6 weeks.
Key exclusion criteria (13 listed)
- Individuals 86 years of age or older will be excluded.
- Currently taking antipsychotics, monoamine oxidase (MAO) inhibitors, or antidepressant medications other than SSRIs, SNRIs, or bupropion. Allowable bupropion doses for participants will be ≤300mg/day.
- Long-acting opioid pain medications (e.g. oxycodone sustained release, morphine sustained release - which are usually taken at 12 hour intervals) will be allowed if the last dose occurred at least 2 hours before psilocybin administration and the next dose was not scheduled until at least 8 hours after psilocybin administration.
- Participants must agree not to take sildenafil, tadalafil, or similar medications within 72 hours of each psilocybin administration, as these medications may potentiate hypotensive reactions to psilocybin
- Cardiovascular conditions: angina, a clinically significant ECG abnormality (e.g. atrial fibrillation or heart-rate corrected QT interval (QTc) >450msec), Transient Ischemic Attack (TIA) in the last 6 months, stroke, artificial heart valves, or uncontrolled hypertension with resting blood pressure systolic >150 or diastolic >95
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 |
|---|---|---|
| PsilocybinDosing at the first session will be 15 mg/70 kg. For the second session participants will either remain at the initial dose, or increase to 25 mg/70 kg at the discretion of the study team. | Drug | Psilocybin |
Primary outcome
Change in Cornell Scale for Depression in Dementia (CSDD) score
Time frame: Baseline and 1 week after second psilocybin session
The Cornell Scale for Depression in Dementia (CSDD) is administered via patient and informant interviews to assess the presence and severity of depressive mood and behavioral symptoms during the past week. Has 19 items, each scored from 0 to 2 with higher scores indicating severe symptom.Total score range from 0 to 38.
1 secondary outcome
Change in Quality of Life Alzheimer's Disease (QOL-AD) scale score
Time frame: Baseline and 2 weeks after second psilocybin 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 4 Sep 2026.
- Study information and application formLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Depressive Symptoms
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
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
Active, not recruiting
NYUCI-ES: Psychosocial Intervention to Improve Health Outcomes for Chinese and Korean ADRD Caregivers
Dementia Caregivers, Diabetes
RecruitingPhase 1
Ketamine Pharmacokinetics and Pharmacodynamics for Postpartum Depression and Pain After Cesarean Delivery
Pain, Postpartum Depression
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.
Albert Garcia-Romeu, PhD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Psilocybin in people with Depressive Symptoms and Depression, run by Johns Hopkins 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 7 inclusion and 13 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: looking for participants now, as of the sponsor's last update on 4 Sep 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Contact Ian Geithner, MPS (4105505466, igeithn1@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Cornell Scale for Depression in Dementia (CSDD) score (time frame: Baseline and 1 week after second psilocybin 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 4 Sep 2026.