Clinical TrialNeurodegenerative DisordersPsilocybinKetaminePlaceboCompleted

A study to investigate the effects of repeated low doses of psilocybin and ketamine on cognitive and emotional dysfunctions in Parkinson’s disease and to understand its mechanism of action

Randomised, double-blind, placebo-controlled crossover Phase II trial (n=34) comparing repeated low oral doses of psilocybin (5 mg) and ketamine (35 mg) versus placebo in people with Parkinson’s disease to assess effects on affect, cognition and biological markers.

Target Enrollment
34 participants
Study Type
Phase II interventional
Design
Randomized, double Blind

Detailed Description

This therapeutic exploratory randomised double-blind crossover trial tests repeated low-dose oral psilocybin and ketamine versus placebo in people with Parkinson’s disease to evaluate changes in positive and negative affect and related cognitive and biological outcomes.

Secondary outcomes include well-being, emotional and cognitive attention (computer tasks), neuroplasticity biomarkers, memory and executive function measures, emotion regulation, Parkinson’s symptom severity, microbiome and immune markers, and endocannabinoid concentrations.

Single-site in the Netherlands; participants were adults (including older adults). The primary endpoint is change in affect scores after completing all three treatment conditions.

Study Arms & Interventions

Psilocybin low-dose

experimental

Oral low-dose psilocybin capsules (repeated dosing condition) in a crossover design.

Interventions

  • Psilocybin5 mg
    via Oral• repeated low doses

    Capsule formulation; repeated small-dose treatment condition.

Ketamine low-dose

experimental

Oral low-dose ketamine capsules (repeated dosing condition) in a crossover design.

Interventions

  • Ketamine35 mg
    via Oral• repeated low doses

    Capsule formulation; repeated small-dose treatment condition.

Placebo

inactive

Matching placebo capsule in crossover design.

Interventions

  • Placebo
    via Oral• repeated dosing

    Matching capsule placebo.

Participants

Ages
18 – 99
Sexes
Male & Female

Inclusion Criteria

  • At least 18 years of age.
  • Diagnosed with Parkinson’s disease with evidence (e.g., letter from a medical doctor or DaT-scan).
  • Underwent a DaT scan as part of the diagnostic process.
  • Able to provide details about disease duration or medical records.
  • Free from conventional Parkinson medication (e.g., Levodopa, dopamine agonist, amantadine, adenosine A2A antagonist, COMT inhibitors, anticholinergic drugs, MAO inhibitors).
  • Generally healthy per investigator assessment (medical history, exam, vitals, ECG, haematology, clinical chemistry, urinalysis, serology).
  • Resting pulse/heart rate ≥51 bpm and ≤100 bpm (≥45 bpm for fit participants).
  • Resting systolic BP ≥91 mmHg and ≤140 mmHg; diastolic BP ≥51 mmHg and ≤90 mmHg.
  • Clinical laboratory values within reference ranges or clinically insignificant if borderline.
  • Normal binocular visual acuity (corrected or uncorrected).
  • BMI between 19.5 and 28 kg/m2.
  • Able to communicate in Dutch or English.
  • Written informed consent.

Exclusion Criteria

  • Previous serious adverse reaction to psychedelic drugs (e.g., severe anxiety or panic attacks).
  • Use of conventional Parkinson’s disease medication.
  • Use of other psychiatric medication.
  • History of drug addiction per medical/drug questionnaires and exam.
  • Depression or dementia.
  • Excessive alcohol consumption (>20 units/week).
  • Excessive smoking (>20 cigarettes/week).
  • Current or past psychiatric disorder per medical questionnaire and exam.
  • Hypertension (diastolic >90 mmHg; systolic >140 mmHg).
  • Liver dysfunction.
  • History of cardiac dysfunction (arrhythmia, ischaemic heart disease, etc.).
  • Pregnancy or lactation.

Study Details

Locations

Netherlands

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