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Psilocybin Microdosing for Mood and Cognition

This study is looking at how small, regular doses of psilocybin (from Psilocybe cubensis mushrooms) affect your mood, thinking skills (cognition), and overall well-being, compared to a placebo (an inactive capsule). Researchers will also use MRI scans to see if there are any brain changes. You might be able to join if you are between 21 and 40 years old, have never used psychedelics, and can read and speak English. Women who can have children must be using effective birth control. The study hopes to see if psilocybin microdosing can improve mood and thinking without causing psychedelic experiences. This could help future research into using psychedelics for conditions like depression. The study is currently recruiting participants.

Study design
This is a double-blind study, meaning neither you nor the researchers will know if you are receiving psilocybin or placebo. It plans to enroll 20 participants.
What's involved
You would take either psilocybin or placebo capsules three times a week for four weeks. Your mood, thinking, and well-being will be assessed, and you will have MRI scans.
Compensation
Not stated in the trial record.
Follow-up
Your mood, cognition, and depression levels will be measured from enrollment to the end of treatment at 8 weeks.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT07449351

Psilocybin Microdosing on Cognition, Mood and Quality of Life

Not Yet Recruiting
EARLY_PHASE1Ages 21–40InterventionalBasic science
Yale University
~20 participants
Updated 2026-06-23 on ClinicalTrials.gov
What's tested:PsliocybinPlacebo

At a glance

Recruiting sites
0 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
The Complex Working Memory Span (CWMS) Task- fMRI measure
Measured over From enrollment to end of treatment at 8 weeks.
+13 more outcomes measured

Conditions

Psychedelic Microdosing Effects on Mood, Cognition, Subjective Well-being and MRI

Explore related trials

Healthy Volunteer

Where it's being run

1 sites across 1 states
Connecticut1

Study leadership

  • Godfrey Pearlson, MD · PRINCIPAL_INVESTIGATOR · Yale University

Who to contact

Godfrey Pearlson, MD
[email protected]
860-545-7757
Email the study team

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Do you actually qualify for this trial?

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Eligibility criteria

Inclusion

No history of psychedelic use
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

Exclusion

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
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)

What this trial measures

  • The Complex Working Memory Span (CWMS) Task- fMRI measureFrom 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)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 InventoryFrom 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 InventoryFrom 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 MeasureFrom 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 BatteryFrom 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/ MindLampFrom 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 TestFrom 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 TestFrom 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 TestFrom 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 ExamFrom 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 testFrom 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 BatteryFrom 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)From enrollment to end of treatment at 8 weeks.

    Assessing synaptic plasticity in MRI