Psychedelic Microdosing Effects on Mood, Cognition, Subjective Well-being and MRIEarly Phase 1NCT07449351
Psilocybin Microdosing on Cognition, Mood and Quality of Life
A Early Phase 1 study testing Psliocybin in people with Psychedelic Microdosing Effects on Mood, Cognition, Subjective Well-being and MRI, run by Yale University at 1 site in United States.
Trial summary
This study is being conducted to evaluate how of 30 days of intermittently microdosed psilocybin affects mood, cognition, subjective well-being and structural/functional MRI results compared to a placebo. Read more about this study
- Who is it for?
- Ages 21 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Psychedelic Microdosing Effects on Mood, Cognition, Subjective Well-being and MRI
- What is being tested?
- Psliocybin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2026to 1 Apr 2028
- 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 21 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- No history of psychedelic use OR
- No use within 10 years, less than or equal to 7x in life OR
- No use within 5 years, less than or equal to 3x in life
- Able to read, speak, and understand English
- Able and willing to provide written informed consent, and willing to commit to study protocol
- Women of childbearing potential must be on a highly effective birth control method
- Must have smartphone compatible with mindLAMP app
Who cannot join
- Positive screen for recreational drugs or alcohol on test day will result in rescheduling the appointment
- Current mood, developmental, or psychotic disorders (e.g., schizophrenia, affective disorders) per DSM-V
- Current or past alcohol or substance use disorder per DSM-V
- IQ <70 on the Weschler Abbreviated Scale of Intelligence
- Serious medical, neuro-ophthalmological, or neurological illness (e.g., cancer, seizure disorders, encephalopathy)
- Current pregnancy, breastfeeding, or ineffective birth control methods
Show all 26Show fewer
- History of head trauma with loss of consciousness lasting >30 minutes or concussion in last 30 days
- Any medical/neurological condition that could compromise neurocognitive performance (e.g., epilepsy, multiple sclerosis, fetal alcohol syndrome)
- Anyone deemed unsafe to study personnel for any reason; e.g., suicidal ideation
- Focal brain lesion seen on structural MRI
- MRI contraindications (e.g., implanted metallic object, severe claustrophobia)
- Clinically significant risk of suicidality, as determined by a score of 4 or higher on the suicidal ideation subscale of C-SSRS (past 6 months) or any suicidal behavior (lifetime)
- Currently taking a monoamine oxidase inhibitor, tricyclic antidepressant, other non-SSRI or non-SNRI antidepressants, an antipsychotic or a mood stabilizer
- Family history of schizophrenia or schizoaffective disorder (first degree relatives), or bipolar disorder type 1 (first degree relatives)
- Diagnosis of arrhythmia or ongoing cardiovascular disorder
- Sustained clinically relevant abnormal heart rate (resting supine heart rate >100 bpm) or blood pressure (resting supine sustolic blood pressure (SBP) above 140mmHg or diastolic blood pressure (DBP) above 90mmHg) at screening
- Clinically relevant abnormal laboratory results, 12-lead ECG, vital signs, cardiopulmonary compromise as detected by echocardiogram, or other physical findings
- Presence of more than mild regurgitant lesions in any position and left ventricular ejection fraction < 35 %
- Evidence of pulmonary vascular disease demonstrated by right ventricular systolic pressure >30mmHg
- Currently taking any GLP-1
- Study Discontinuation Criteria
- Development of active suicidal or homicidal ideation with plan and intent
- Worsening in mood symptoms, or development of psychotic symptoms that in the opinion of the investigators requires discontinuation
- Development of severe or life-threatening medical condition
- Psychiatric or medical hospitalization or incarceration post-screening
- Adverse reaction to study drug that in the opinion of the investigators requires discontinuation (e.g. acute, clinically significant hypertension, cardiac toxicity, non-acute significant negative psychological changes)
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
Olin Neuropsychiatry Research Center
Hartford, Connecticut, 06106
Diana King, 860-545-7563, diana.king@hhchealth.org
About this study
Official title: Effects of Psilocybin Microdosing on Cognition, Mood and Quality of Life: A Pilot Study
This study is being conducted to evaluate how of 30 days of intermittently microdosed psilocybin affects mood, cognition, subjective well-being and structural/functional MRI results compared to a placebo. Investigators hypothesize that compared to placebo, 30 days of intermittently microdosed psilocybin will produce observable changes in mood, cognition, subjective well-being and MRI, in the absence of psychedelic experiences.
Read the detailed description
This study is being conducted to evaluate the effects of 30 days of intermittently microdosed psilocybin in a parallel arm double-blind manner on mood, cognition, subjective well-being and structural/functional MRI compared to placebo, using validated psychological assessments and cognitive tests. Investigators hypothesize that compared to placebo, 30 days of intermittently microdosed psilocybin will produce observable changes in mood, cognition, subjective well-being and MRI, in the absence of psychedelic experiences.
Demonstrating significant results in a population of healthy psychedelic non-users will establish a strong precedent for studying the effects of microdosing psychedelics in patient populations, such as those with treatment-resistant depression. Showing that microdosing minimizes risk of adverse outcomes with psychedelic treatment while maintaining beneficial effects would provide useful information relevant to clinical research in psychedelic-assisted psychotherapy. In addition to investigating claims that microdosing psychedelics may improve cognition and mood, this study also aims to test the hypothesis that these effects including those measurable at a brain level may persist beyond the course of the 30 days of the study. There are few to no studies that assessed the longevity of psychedelic effects on the majority of the above measures, so the proposed study may further establish the longer-term benefits of microdosing. The use of structural and functional magnetic resonance imaging (fMRI) will elucidate the mechanisms by which microdosing may be exerting its effects on mood and cognition. Because this is a relatively understudied area, information gleaned from this study will provide service in informing the field in general.
- Being tested
- Psliocybin, Placebo
- Keywords
- Psychedelics, Psilocybin, MRI, fMRI, Microdosing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PsliocybinDrug
2.0mg powdered psilocybin derived from Psilocybe cubensis mushrooms, in capsules, provided three times weekly for four weeks
PlaceboDrug
0mg matching capsules, provided three times weekly for four weeks
| Study group | Role | What they receive |
|---|---|---|
| Psychedelic group | Active comparator | An imperceptible dose of psilocybin in capsules will be administered to subjects three times weekly for four weeks. Assessments will be conducted once weekly. After 30 days of a steady dose of psilocybin, subjects will be re-assessed with baseline measures. Receives: Drug: Psliocybin |
| Placebo group | Placebo comparator | An dose of placebo in capsules, identical to the active, will be administered to subjects three times weekly for four weeks. Assessments will be conducted once weekly. After 30 days of a steady dose of psilocybin, subjects will be re-assessed with baseline measures. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Complex Working Memory Span (CWMS) Task- fMRI measure
CWMS Task assesses immediate plus delayed recall and working memory by assessing working memory capacity by presenting a list of stimuli to be recalled while simultaneously performing a secondary task. This task uses a fully crossed design which includes both same-domain CWMS conditions (e.g. verbal storage combined with verbal processing) as well as cross-domain CWMS conditions (e.g., verbal storage combined with spatial processing). BOLD signal Infrontal lobe.
Measured: From enrollment to end of treatment at 8 weeks.
NEO-Five-Factor-Inventory (NEO-FFI)
The NEO-FFI is a self-description questionnaire with 60 items for the measurement of the "big five": neuroticism, extraversion, openness, agreeableness, and consciousness. It uses a 5-point Likert scale ranging from "completely disagree" to "fully agree.
Measured: From enrollment to end of treatment at 8 weeks.
Beck Depression Inventory
This scale has a total of 21 items. Each item is scored from 0-3 points, and the total score ranges from 0-63 points. The higher the score, the higher the degree of depression.
Measured: From enrollment to end of treatment at 8 weeks.
Beck Anxiety Inventory
Beck Anxiety Inventory is a 21-item self-reported questionnaire which measures the existenceand severity of symptoms of anxiety. Each of the 21 items on BAI tool represents an anxiety symptom. A total score of 0 - 7 is interpreted as a "Minimal" level of anxiety; 8 - 15 as "Mild"; 16 - 25 as "Moderate", and 26 - 63 as "Severe".
Measured: From enrollment to end of treatment at 8 weeks.
Harvard Flourishing Measure
12 questions, rating from 0 to 10 per question, sum score to calculate the 'flourish measure' will be used.
Measured: From enrollment to end of treatment at 8 weeks.
NIH Toolbox Cognitive Battery
Cognitive function will be assessed using the NIH Toolbox Cognition Battery, administered on an iPad.
Measured: From enrollment to end of treatment at 8 weeks.
Ecological Momentary Assessments (EMAs) w/ MindLamp
Once-daily questions (EMAs) about mood and sleep will be sent via the MindLamp smartphone app.
Measured: From enrollment to end of treatment at 8 weeks.
Switching Stroop Test
Stroop task measures response inhibition or response interference control. Participants will be shown a series of word colors that are either congruent or incongruent with the color of the word itself. The participant will be asked to respond to the color of the word and not the word itself. Responses are made with the keyboard. The incongruent condition is the more difficult condition of the two. Reaction time is recorded and a cost score is calculated, with shorter cost scores indicating better performance.
Measured: From enrollment to end of treatment at 8 weeks.
Penn Conditional Exclusion Test
Neurocognition measure of reasoning \& problem solving in PennCNB. Scores will be transformed into z-scores. The key score will assess perseverative errors. Lowest score = 0, no max score. A higher score is correlated with worse performance, i.e. more perseverative errors.
Measured: From enrollment to end of treatment at 8 weeks.
Flanker Inhibitory Control and Attention Test
This test is designed to evaluate an individual's ability to concentrate their attention while inhibiting automatic response tendencies that could potentially hinder goal achievement. This is the percent correct outcome from this assessment.
Measured: From enrollment to end of treatment at 8 weeks.
Face Name Associated Memory Exam
The score ranges from 0 to 130, with a higher score indicating better speed of processing.
Measured: From enrollment to end of treatment at 8 weeks.
9-hole pegboard dexterity test
The Nine-Hole Peg Test (9HPT) is used to measure finger dexterity in patients with various neurological diagnoses. Time to complete the test as quickly as possible
Measured: From enrollment to end of treatment at 8 weeks.
NIH Toolbox Cognitive Battery
The Nine-Hole Peg Test (9HPT) is used to measure finger dexterity in patients with various neurological diagnoses. Time to complete the test as quickly as possible
Measured: From enrollment to end of treatment at 8 weeks.
Neurite Orientation Dispersion and Density Imaging (NODDI)
Assessing synaptic plasticity in MRI
Measured: From enrollment to end of treatment at 8 weeks.
Secondary outcomes (2)
Complex Working Memory Span task
Measures ability to juggle holding information (storage) and doing something with it (processing) at the same time. Percent accuracy will be reported.
Measured: From enrollment to end of treatment at 8 weeks.
fMRI
Mean BOLD signal
Measured: From enrollment to end of treatment at 8 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2026
- Study start1 Oct 2026 (estimated)
- Primary completion1 Apr 2028 (estimated)
- Study completion1 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Psychedelic Microdosing Effects on Mood, Cognition, Subjective Well-being and MRIStudies 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Hartford HealthCare
- Responsible party
- Principal investigator, Godfrey Pearlson, Yale University
- Investigators
- Godfrey Pearlson, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07449351
- Sponsor's protocol ID
- HHC-2025-0200
- Status last verified
- Jun 2026
- First submitted
- 26 Feb 2026
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Psilocybin Microdosing on Cognition, Mood and Quality of Life: A Pilot Study
- ClinicalTrials.gov ID
- NCT07449351
- Acronym / sponsor ID
- HHC-2025-0200
- Keywords
- Psychedelics, Psilocybin, MRI, fMRI, Microdosing
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Hartford HealthCare
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 1 Apr 2028 (estimated)
- Study completion
- 1 Apr 2028 (estimated)
- First posted
- 4 Mar 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 evaluate how of 30 days of intermittently microdosed psilocybin affects mood, cognition, subjective well-being and structural/functional MRI results compared to a placebo. Investigators hypothesize that compared to placebo, 30 days of intermittently microdosed psilocybin will produce observable changes in mood, cognition, subjective well-being and MRI, in the absence of psychedelic experiences.
Detailed description
This study is being conducted to evaluate the effects of 30 days of intermittently microdosed psilocybin in a parallel arm double-blind manner on mood, cognition, subjective well-being and structural/functional MRI compared to placebo, using validated psychological assessments and cognitive tests. Investigators hypothesize that compared to placebo, 30 days of intermittently microdosed psilocybin will produce observable changes in mood, cognition, subjective well-being and MRI, in the absence of psychedelic experiences.
Demonstrating significant results in a population of healthy psychedelic non-users will establish a strong precedent for studying the effects of microdosing psychedelics in patient populations, such as those with treatment-resistant depression. Showing that microdosing minimizes risk of adverse outcomes with psychedelic treatment while maintaining beneficial effects would provide useful information relevant to clinical research in psychedelic-assisted psychotherapy. In addition to investigating claims that microdosing psychedelics may improve cognition and mood, this study also aims to test the hypothesis that these effects including those measurable at a brain level may persist beyond the course of the 30 days of the study. There are few to no studies that assessed the longevity of psychedelic effects on the majority of the above measures, so the proposed study may further establish the longer-term benefits of microdosing. The use of structural and functional magnetic resonance imaging (fMRI) will elucidate the mechanisms by which microdosing may be exerting its effects on mood and cognition. Because this is a relatively understudied area, information gleaned from this study will provide service in informing the field in general.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Psychedelic group | Active comparator | Drug: PsliocybinAn imperceptible dose of psilocybin in capsules will be administered to subjects three times weekly for four weeks. Assessments will be conducted once weekly. After 30 days of a steady dose of psilocybin, subjects will be re-assessed with baseline measures. |
| Placebo group | Placebo comparator | Drug: PlaceboAn dose of placebo in capsules, identical to the active, will be administered to subjects three times weekly for four weeks. Assessments will be conducted once weekly. After 30 days of a steady dose of psilocybin, subjects will be re-assessed with baseline measures. |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- No history of psychedelic use OR
- No use within 10 years, less than or equal to 7x in life OR
- No use within 5 years, less than or equal to 3x in life
- Able to read, speak, and understand English
- Able and willing to provide written informed consent, and willing to commit to study protocol
Key exclusion criteria (26 listed)
- Positive screen for recreational drugs or alcohol on test day will result in rescheduling the appointment
- Current mood, developmental, or psychotic disorders (e.g., schizophrenia, affective disorders) per DSM-V
- Current or past alcohol or substance use disorder per DSM-V
- IQ <70 on the Weschler Abbreviated Scale of Intelligence
- Serious medical, neuro-ophthalmological, or neurological illness (e.g., cancer, seizure disorders, encephalopathy)
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 |
|---|---|---|
| Psliocybin2.0mg powdered psilocybin derived from Psilocybe cubensis mushrooms, in capsules, provided three times weekly for four weeks | Drug | Psychedelic group |
| Placebo0mg matching capsules, provided three times weekly for four weeks | Drug | Placebo group |
Primary outcome
The Complex Working Memory Span (CWMS) Task- fMRI measure
Time frame: From enrollment to end of treatment at 8 weeks.
CWMS Task assesses immediate plus delayed recall and working memory by assessing working memory capacity by presenting a list of stimuli to be recalled while simultaneously performing a secondary task. This task uses a fully crossed design which includes both same-domain CWMS conditions (e.g. verbal storage combined with verbal processing) as well as cross-domain CWMS conditions (e.g., verbal storage combined with spatial processing). BOLD signal Infrontal lobe.
NEO-Five-Factor-Inventory (NEO-FFI)
Time frame: From enrollment to end of treatment at 8 weeks.
The NEO-FFI is a self-description questionnaire with 60 items for the measurement of the "big five": neuroticism, extraversion, openness, agreeableness, and consciousness. It uses a 5-point Likert scale ranging from "completely disagree" to "fully agree.
Beck Depression Inventory
Time frame: From enrollment to end of treatment at 8 weeks.
This scale has a total of 21 items. Each item is scored from 0-3 points, and the total score ranges from 0-63 points. The higher the score, the higher the degree of depression.
Beck Anxiety Inventory
Time frame: From enrollment to end of treatment at 8 weeks.
Beck Anxiety Inventory is a 21-item self-reported questionnaire which measures the existenceand severity of symptoms of anxiety. Each of the 21 items on BAI tool represents an anxiety symptom. A total score of 0 - 7 is interpreted as a "Minimal" level of anxiety; 8 - 15 as "Mild"; 16 - 25 as "Moderate", and 26 - 63 as "Severe".
Harvard Flourishing Measure
Time frame: From enrollment to end of treatment at 8 weeks.
12 questions, rating from 0 to 10 per question, sum score to calculate the 'flourish measure' will be used.
NIH Toolbox Cognitive Battery
Time frame: From enrollment to end of treatment at 8 weeks.
Cognitive function will be assessed using the NIH Toolbox Cognition Battery, administered on an iPad.
Ecological Momentary Assessments (EMAs) w/ MindLamp
Time frame: From enrollment to end of treatment at 8 weeks.
Once-daily questions (EMAs) about mood and sleep will be sent via the MindLamp smartphone app.
Switching Stroop Test
Time frame: From enrollment to end of treatment at 8 weeks.
Stroop task measures response inhibition or response interference control. Participants will be shown a series of word colors that are either congruent or incongruent with the color of the word itself. The participant will be asked to respond to the color of the word and not the word itself. Responses are made with the keyboard. The incongruent condition is the more difficult condition of the two. Reaction time is recorded and a cost score is calculated, with shorter cost scores indicating better performance.
Penn Conditional Exclusion Test
Time frame: From enrollment to end of treatment at 8 weeks.
Neurocognition measure of reasoning \& problem solving in PennCNB. Scores will be transformed into z-scores. The key score will assess perseverative errors. Lowest score = 0, no max score. A higher score is correlated with worse performance, i.e. more perseverative errors.
Flanker Inhibitory Control and Attention Test
Time frame: From enrollment to end of treatment at 8 weeks.
This test is designed to evaluate an individual's ability to concentrate their attention while inhibiting automatic response tendencies that could potentially hinder goal achievement. This is the percent correct outcome from this assessment.
Face Name Associated Memory Exam
Time frame: From enrollment to end of treatment at 8 weeks.
The score ranges from 0 to 130, with a higher score indicating better speed of processing.
9-hole pegboard dexterity test
Time frame: From enrollment to end of treatment at 8 weeks.
The Nine-Hole Peg Test (9HPT) is used to measure finger dexterity in patients with various neurological diagnoses. Time to complete the test as quickly as possible
NIH Toolbox Cognitive Battery
Time frame: From enrollment to end of treatment at 8 weeks.
The Nine-Hole Peg Test (9HPT) is used to measure finger dexterity in patients with various neurological diagnoses. Time to complete the test as quickly as possible
Neurite Orientation Dispersion and Density Imaging (NODDI)
Time frame: From enrollment to end of treatment at 8 weeks.
Assessing synaptic plasticity in MRI
2 secondary outcomes
Complex Working Memory Span task
Time frame: From enrollment to end of treatment at 8 weeks.
fMRI
Time frame: From enrollment to end of treatment at 8 weeks.
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 24 Sep 2026.
- Individual participant dataSharing planned: No
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.
Godfrey Pearlson, 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 Early Phase 1 study testing Psliocybin in people with Psychedelic Microdosing Effects on Mood, Cognition, Subjective Well-being and MRI, 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 7 inclusion and 26 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: opening soon, as of the sponsor's last update on 24 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. Some participants in this study may receive a placebo. 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 Godfrey Pearlson, MD (860-545-7757, godfrey.pearlson@hhchealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Complex Working Memory Span (CWMS) Task- fMRI measure (time frame: From enrollment to end of treatment at 8 weeks.). The study lists 14 primary outcomes in all. 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 24 Sep 2026.