Anhedonia in Healthy VolunteersPhase 1OAD1NCT07386730
A Study of Psychedelics in Healthy Older Adults With Low Well-being
A Phase 1 study testing Psilocybin (drug) and Dextromethorphan (DXM) in people with Anhedonia in Healthy Volunteers and Older Adults (50-90 Years), run by Jennifer Mitchell at 1 site in United States.
Trial summary
This study is being conducted to understand changes in brain activity following administration of two different drugs (Psilocybin and Dextromethorphan) in older adults with low well-being. The main questions it aims to answer are, does psilocybin: 1. Read more about this study
- Who is it for?
- Ages 50 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Anhedonia in Healthy Volunteers, Older Adults (50-90 Years)
- What is being tested?
- Psilocybin (drug) and Dextromethorphan (DXM)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2026to Feb 2030
- 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 50 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Are between 50-85 years inclusive at time of consent signing
- Have below-average well-being, defined by the World Health Organization Well-Being Index (WHO-5)
- Have no cognitive impairments, indicated by a Mini-Mental State Examination (MMSE) score >24
- Have an identified willing contact person with at least weekly contact with the participant to be able to provide meaningful information about the participant's daily function and able to pick up the study participant at the end of the Dosing Visit
- Participants assigned female sex at birth must be non-lactating, and post-menopausal, defined as a period of over 12 months since the last menstrual period, or otherwise physically unable to become pregnant
- Participants assigned male sex at birth must 1) refrain from sperm donation for 3 months after the Dosing Visit, and 2) if engaging in sexual activities that may result in pregnancy, must use a condom, plus their partner of childbearing potential must use a second, highly effective form of contraception for 3 months after the Dosing Visit
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- Be proficient in English
- Are able and willing to provide consent as assessed by comprehension questions in informed consent process
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Ability to swallow oral medications (capsules)
Who cannot join
- General:
- Have a known allergic or severe reaction to Psilocybin, Dextromethorphan, or any of the non-active components of the IMP capsules
- Insufficient ability to report on symptoms to make a valid assessment on any required instrument
- Have a condition or presence of clinical feature which, in the opinion of the investigators might interfere with or prevent appropriate study participation or interfere with data interpretation
- MRI Exclusions:
- Any implanted object or device that poses a safety risk or could interfere with MRI scanning (e.g. aneurysm clips, cardiac pacemakers, defibrillators, neurostimulators, cochlear implants, spinal cord stimulators, insulin or infusion pumps, metallic prostheses or fragments, heart valves, vascular stents, or shunts. surgical staples, clips, or joint replacements, radiation seeds, medication patches containing metal, or any other metallic or electronic implants)
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- History of metallic injury to the eyes or body, or those with tattoos containing metallic ink, permanent makeup, or body piercings that cannot be removed.
- Any condition that poses a safety risk or could interfere with MRI scanning (e.g. severe claustrophobia or motion disorders or breathing problems, etc)
- Psychiatric:
- •History of hallucinogen persisting perception disorder (HPPD) (as per DSM-5 criteria)
- Cardiovascular:
- Clinically significant cardiovascular conditions e.g., clinically significant EKG abnormalities, transient ischemic attack in the last 6 months, history of hemorrhagic stroke, history of myocardial infarction within 1 year of signing informed consent form (ICF)
- Baseline (heart rate < 60 bpm or > 90 bpm at screening or pre-dose
- Baseline hypertension (≥140 SBP or ≥90 DBP), after repeated measurements
- QTc Interval > 450msec on 12-lead EKG. Note: If QT-prolonging medications are started or increased in dose after enrollment and prior to dosing visit, a repeat EKG must be done >12-hours after this change to assure continued safe enrollment in the trial
- Clinically significant arrhythmia (e.g., uncontrolled atrial fibrillation, or untreated supraventricular tachycardia)
- Any current condition where physical activity is associated with palpitations, anginal pain or syncope
- General health:
- Major systemic disorders, including seizure, insulin dependent diabetes mellitus, recent history (last 12 months) of advanced cancer or its treatment (radiation therapy or chemotherapy), had major surgery within 6 months from screening or plans to have surgery while enrolled in the study
- Inadequate hepatic function as determined by total bilirubin or alkaline phosphatase >3x institutional upper limit of normal; or aspartate aminotransferase (AST) or alanine transaminase (ALT) >3x institutional upper limit of normal. However, participants with Gilbert syndrome are allowed to enroll
- Inadequate renal function as determined by estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (based on the MDRD equation)
- Participant is at increased risk of falls
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
University of California San Francisco, Sandler Neuroscience Building
San Francisco, California, 94158
Gabriella Mace, 415-707-5399, agingandpsychedelics@ucsf.edu
Lorenzo Pasquini, PhD
About this study
Official title: A Double Blind, Randomized Trial Investigating the Safety, Feasibility, and Mechanisms of Psychedelics in Healthy Older Adults With Low Well-being as Moderated by Biomarkers for Preclinical Alzheimer's Disease
This study is being conducted to understand changes in brain activity following administration of two different drugs (Psilocybin and Dextromethorphan) in older adults with low well-being.
The main questions it aims to answer are, does psilocybin:
Read more
- Acutely increase complexity of EEG activity in older adults with low well-being, as modulated by the presence of biomarkers of Alzheimer's disease (AD) pathology.
- Longitudinally decrease plasma markers of neuroinflammation, as modulated by the presence of biomarkers of AD pathology.
- Explore longitudinal changes in autonomic physiology via wearable recording devices as well as longitudinal structural and functional brain changes measured in the MRI
Participants will be in the study for up to 3 months, which will include 3 to 4 in person visits and 3 to 4 remote visits. Most visits will be between 1 to 3 hours, but the dosing visit will last a minimum of 8 hours and could be as long as 12 hours. During the dosing visit, all participants will receive a single dose of the study drugs and dosages listed below.
Researchers will compare participants who receive the following drug options:
- A low-to-moderate dose of Psilocybin (5-10 mg)
- A moderate-to-high dose of Psilocybin (25-30 mg)
- A low-to-moderate dose of Dextromethorphan (30-60 mg)
- A moderate-to-high dose of Dextromethorphan (80-90 mg)
- Being tested
- Psilocybin (drug), Dextromethorphan (DXM)
- Keywords
- Psilocybin, Dextromethorphan, older adults, well-being, EEG, MRI, neuroinflammation, Alzheimer's disease plasma markers, wearables
- Medical subject headings
- Neuroinflammatory Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Psilocybin (drug)Drug
Participants will receive either Psilocybin or Dextromethorphan in this clinical trial
Dextromethorphan (DXM)Drug
Participants will receive either Psilocybin or Dextromethorphan in this clinical trial
| Study group | Role | What they receive |
|---|---|---|
| A low-to-moderate dose of Psilocybin (5-10 mg) | Experimental | A single low-to-moderate dose of Psilocybin (5-10 mg) Receives: Drug: Psilocybin (drug) |
| A moderate-to-high dose of Psilocybin (25-30 mg) | Experimental | A single moderate-to-high dose of Psilocybin (25-30 mg) Receives: Drug: Psilocybin (drug) |
| A low-to-moderate dose of Dextromethorphan (30-60 mg) | Experimental | A single low-to-moderate dose of Dextromethorphan (30-60 mg) Receives: Drug: Dextromethorphan (DXM) |
| A moderate-to-high dose of Dextromethorphan (80-90 mg) | Experimental | A single moderate-to-high dose of Dextromethorphan (80-90 mg) Receives: Drug: Dextromethorphan (DXM) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute changes in EEG-based ESBA
Compare acute changes in EEG-based Lempel Ziv complexity (pre- to post-dose, arbitrary unit) between the four study arms, with the presence of biomarkers of AD pathology used in the statistical analyses as a moderator. Lempel-Ziv complexity in EEG is a non-linear analysis tool that quantifies the amount of entropy of spontaneous brain activity (ESBA).
Measured: Pre- to post-dose two hours later
Secondary outcomes (1)
Changes in TNF-alpha
Compare changes in a biomarkers of neuroinflammation (TNF-alpha) psilocybin across the four study arms, with the presence of biomarkers of AD pathology used in the statistical analyses as a moderator. Reference Range 0.56-1.40 pg/mL
Measured: Screening to three weeks post dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2026
- Study start1 Jun 2026
- Primary completionFeb 2030 (estimated)
- Study completionFeb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anhedonia in Healthy VolunteersStudies of the same condition, open and under way.
- 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
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jennifer Mitchell
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jennifer Mitchell, University of California, San Francisco
- Investigators
- Lorenzo Pasquini, PhD, Principal investigator, University of California, San FranciscoJennifer Mitchell, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07386730
- Sponsor's protocol ID
- 25-45261
- Other IDs
- A146672
- Acronym
- OAD1
- Status last verified
- Dec 2025
- First submitted
- 20 Jan 2026
- Last updated
- 9 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 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double Blind, Randomized Trial Investigating the Safety, Feasibility, and Mechanisms of Psychedelics in Healthy Older Adults With Low Well-being as Moderated by Biomarkers for Preclinical Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT07386730
- Acronym / sponsor ID
- OAD1 / 25-45261
- Keywords
- Psilocybin, Dextromethorphan, older adults, well-being, EEG, MRI, neuroinflammation, Alzheimer's disease plasma markers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Jennifer MitchellUniversity, hospital or other
- Study start
- 1 Jun 2026 (actual)
- Primary completion
- Feb 2030 (estimated)
- Study completion
- Feb 2030 (estimated)
- First posted
- 4 Feb 2026 (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 study is being conducted to understand changes in brain activity following administration of two different drugs (Psilocybin and Dextromethorphan) in older adults with low well-being.
The main questions it aims to answer are, does psilocybin:
- Acutely increase complexity of EEG activity in older adults with low well-being, as modulated by the presence of biomarkers of Alzheimer's disease (AD) pathology.
- Longitudinally decrease plasma markers of neuroinflammation, as modulated by the presence of biomarkers of AD pathology.
- Explore longitudinal changes in autonomic physiology via wearable recording devices as well as longitudinal structural and functional brain changes measured in the MRI
Participants will be in the study for up to 3 months, which will include 3 to 4 in person visits and 3 to 4 remote visits. Most visits will be between 1 to 3 hours, but the dosing visit will last a minimum of 8 hours and could be as long as 12 hours. During the dosing visit, all participants will receive a single dose of the study drugs and dosages listed below.
Researchers will compare participants who receive the following drug options:
- A low-to-moderate dose of Psilocybin (5-10 mg)
- A moderate-to-high dose of Psilocybin (25-30 mg)
- A low-to-moderate dose of Dextromethorphan (30-60 mg)
- A moderate-to-high dose of Dextromethorphan (80-90 mg)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| A low-to-moderate dose of Psilocybin (5-10 mg) | Experimental | Drug: Psilocybin (drug)A single low-to-moderate dose of Psilocybin (5-10 mg) |
| A moderate-to-high dose of Psilocybin (25-30 mg) | Experimental | Drug: Psilocybin (drug)A single moderate-to-high dose of Psilocybin (25-30 mg) |
| A low-to-moderate dose of Dextromethorphan (30-60 mg) | Experimental | Drug: Dextromethorphan (DXM)A single low-to-moderate dose of Dextromethorphan (30-60 mg) |
| A moderate-to-high dose of Dextromethorphan (80-90 mg) | Experimental | Drug: Dextromethorphan (DXM)A single moderate-to-high dose of Dextromethorphan (80-90 mg) |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Are between 50-85 years inclusive at time of consent signing
- Have below-average well-being, defined by the World Health Organization Well-Being Index (WHO-5)
- Have no cognitive impairments, indicated by a Mini-Mental State Examination (MMSE) score >24
- Have an identified willing contact person with at least weekly contact with the participant to be able to provide meaningful information about the participant's daily function and able to pick up the study participant at the end of the Dosing Visit
- Participants assigned female sex at birth must be non-lactating, and post-menopausal, defined as a period of over 12 months since the last menstrual period, or otherwise physically unable to become pregnant
Key exclusion criteria (22 listed)
- Have a known allergic or severe reaction to Psilocybin, Dextromethorphan, or any of the non-active components of the IMP capsules
- Insufficient ability to report on symptoms to make a valid assessment on any required instrument
- Have a condition or presence of clinical feature which, in the opinion of the investigators might interfere with or prevent appropriate study participation or interfere with data interpretation
- Any implanted object or device that poses a safety risk or could interfere with MRI scanning (e.g. aneurysm clips, cardiac pacemakers, defibrillators, neurostimulators, cochlear implants, spinal cord stimulators, insulin or infusion pumps, metallic prostheses or fragments, heart valves, vascular stents, or shunts. surgical staples, clips, or joint replacements, radiation seeds, medication patches containing metal, or any other metallic or electronic implants)
- History of metallic injury to the eyes or body, or those with tattoos containing metallic ink, permanent makeup, or body piercings that cannot be removed.
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 |
|---|---|---|
| Psilocybin (drug)Participants will receive either Psilocybin or Dextromethorphan in this clinical trial | Drug | A low-to-moderate dose of Psilocybin (5-10 mg), A moderate-to-high dose of Psilocybin (25-30 mg) |
| Dextromethorphan (DXM)Participants will receive either Psilocybin or Dextromethorphan in this clinical trial | Drug | A low-to-moderate dose of Dextromethorphan (30-60 mg), A moderate-to-high dose of Dextromethorphan (80-90 mg) |
Primary outcome
Acute changes in EEG-based ESBA
Time frame: Pre- to post-dose two hours later
Compare acute changes in EEG-based Lempel Ziv complexity (pre- to post-dose, arbitrary unit) between the four study arms, with the presence of biomarkers of AD pathology used in the statistical analyses as a moderator. Lempel-Ziv complexity in EEG is a non-linear analysis tool that quantifies the amount of entropy of spontaneous brain activity (ESBA).
1 secondary outcome
Changes in TNF-alpha
Time frame: Screening to three weeks post dosing
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 9 Sep 2026.
- Individual participant dataSharing planned: No
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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.
Lorenzo Pasquini, PhD principal investigator
University of California, San Francisco
Jennifer Mitchell, PhD principal investigator
University of California, San Francisco
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 Psilocybin (drug) and Dextromethorphan (DXM) in people with Anhedonia in Healthy Volunteers and Older Adults (50-90 Years), run by Jennifer Mitchell 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 10 inclusion and 22 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 9 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?
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?
Contact Gabriella Mace (415-707-5399, agingandpsychedelics@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute changes in EEG-based ESBA (time frame: Pre- to post-dose two hours later). 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 9 Sep 2026.