Clinical TrialMicrodosingPsilocybinPlaceboNot yet recruiting

Psilocybin Microdosing on Cognition, Mood and Quality of Life

This Phase I, randomised, double-blind, parallel trial (n=20) will study the effects of intermittent psilocybin microdosing on mood, cognition, subjective well‑being and brain structure/function in healthy adults with no history of psychedelic use aged 21–40. The primary aim is basic science: to evaluate whether 30 days of intermittent microdosed psilocybin produces measurable changes on psychological, cognitive and neuroimaging outcomes compared with placebo, in the presumed absence of overt psychedelic experiences. Participants will be randomised to receive either 2 mg powdered psilocybin (from Psilocybe cubensis) in capsules or matching 0 mg placebo capsules three times weekly for four weeks, with weekly assessments and re‑assessment after 30 days of steady dosing; primary outcome measures are assessed from enrolment to end of treatment (8 weeks). Outcomes include task‑based fMRI (Complex Working Memory Span task), structural and diffusion imaging (including NODDI), neuropsychological batteries (NIH Toolbox, Switching Stroop, Flanker, Penn Conditional Exclusion, Face‑Name Associative Memory, 9‑hole pegboard), personality and symptom scales (NEO‑FFI, Beck Depression and Anxiety Inventories, Harvard Flourishing), and ecological momentary assessments via MindLamp. Key eligibility features are no prior psychedelic use, ability to consent, effective contraception for women of childbearing potential, and exclusion for current mood/psychotic disorders, substance use disorders, significant medical/neurological illness or MRI contraindications.

Target Enrollment
20 participants
Study Type
Phase I interventional
Design
Randomized, double Blind

Detailed Description

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.

Study Arms & Interventions

Psychedelic group

experimental

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.

Interventions

  • Psilocybin2 mg
    via Oral• three times weekly for four weeks• 12 doses total

    Unmatched intervention: Psliocybin

Placebo group

inactive

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.

Interventions

  • Placebo0 mg
    via Oral• three times weekly for four weeks• 12 doses total

Participants

Ages
21 – 40
Sexes
Male & Female

Inclusion Criteria

  • 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 Criteria

  • 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)

Study Details

  • Status
    Not yet recruiting
  • Phase
    Phase I
  • Type
    interventional
  • Design
    Randomizeddouble Blind
  • Target Enrollment20 participants
  • Timeline
    Start: 2026-04-01
    End: 2028-04-01
  • Compounds
    PsilocybinPlacebo
  • Topic
    Microdosing

Study Team

Sponsors & Collaborators

Locations

Olin Neuropsychiatry Research Center — Hartford, Connecticut, United States

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