Psilocybin Therapy for Psychological Distress in... — Clinical Trial Details

PsyPal is a randomized, double-blind, low-dose controlled Phase II trial evaluating psilocybin therapy for depressive symptoms and psychological distress in patients with COPD, ALS, MS, or atypical Parkinsonian disorders with at least six months life expectancy.

Participants receive three preparation psychotherapy sessions, two supervised oral psilocybin dosing sessions (experimental: 15 mg then 25 mg; control: 1 mg twice), and five integration sessions; outcomes assessed at 6 weeks, 3 months and 6 months.

Primary endpoint is change in depression severity at 6 weeks after the second dose; secondary and exploratory measures include anxiety, demoralization, quality of life, biomarkers (EEG, blood), health-economic outcomes, and qualitative interviews.

Participants

Ages

18 – 99

Sexes

Male & Female

BMI

Psychosis History

Excluded

Inclusion Criteria

Inclusion Criteria:
1. Patient has to be diagnosed with one of the following four conditions, defined as:
COPD i) Diagnosis by medical specialist ii) Postbronchodilator FEV1/FVC < 0.7 and FEV1 <80% pred iii) ≥ 40 years old iv) ≥ 10 years smoking
ALS i) ALS according to Goldcoast criteria (Shefner et al, Clin Neurophysiol, 2020) ii) ALS-FRS-R subscores of minimum 1 in item 2, 3 and 8, subscore of minimum 2 in item 1, 4 and 10 and a subscore of minimum 3 in item 11 and 12
MS i) Fulfilled diagnostic revised McDonald criteria for MS from 2017 (Thompson et al., 2018) ii) EDSS ≥ 1.0
APD i) Advanced to Late-Stage Parkinson's Disease - patients with a diagnosis of Parkinson's Disease per the MDS clinical diagnosis criteria with evidence of motor and non-motor fluctuations ii) Diseases in the spectrum of Progressive supranuclear palsy (PSP), fulfilling possible and probable criteria, according to the MDS diagnostic criteria iii) Clinically Established and Clinically Probable Multiple System Atrophy (MSA) according to the MDS diagnostic criteria
2. Patient meets ICD-10 criteria for major depressive disorder documented through completion of the mood section of the MINI by a screening psychologist or physician.
3. Patient has a MADRS score of > 19.
4. Patient should have a life expectancy of at least 6 months (assessed by study physician).
5. Patient is at least 18 years of age.
6. Patient has an identified caregiver/support person.
7. Patient is able to read and understand the informed consent and all scales used in a local language; competency procedures for ALS/MS/APD described.
8. Patient is able to and willing to adhere to study requirements, including attending all visits and sessions.
9. Patient is able to ingest capsules.

Exclusion Criteria

Exclusion Criteria:
1. Patient has used a psychedelic substance in the past 6 months (e.g., psilocybin, LSD, 5-MeO-DMT, DMT, ayahuasca or mescaline).
2. Patient is in active treatments for other psychiatric disorders judged to be a more significant clinical problem than depression/distress.
3. Patient meets ICD-10 criteria for schizophrenia spectrum or other psychotic disorders, including major depressive disorder with psychotic features, or bipolar I/II disorder.
4. Any lifetime diagnosis of schizophrenia spectrum or other psychotic disorders.
5. Patient has a first-degree relative with schizophrenia spectrum, bipolar I disorder or other psychotic disorders.
6. Pre-existing psychiatric conditions judged incompatible with safe exposure to psilocybin therapy.
7. Significant suicide risk defined as (1) suicidal ideation with intent to act (MADRS item 10 ≥ 5), (2) suicide attempts within past year, or (3) clinical assessment of significant suicidal risk during interview.
8. Active/current alcohol or drug use disorder.
9. Ongoing treatment with antipsychotic drugs; prohibited agents must be stopped for at least 5x elimination half-life prior to baseline.
10. Unwillingness or inability to pause formal psychotherapy (days 0-42).
11. Neurological conditions expected to conflict with treatment (e.g., intracranial tumour, epilepsy, brain injury).
12. Disease-specific exclusions (unresolved COPD exacerbation, significant cognitive deficits for ALS/MS/APD, dementia for APD, specific functional thresholds).
13. Cardiovascular conditions: recent stroke or MI (<1 year), uncontrolled hypertension (>140/90 mmHg), clinically significant arrhythmia within 1 year, or QTc prolongation exceeding 450 ms (males)/470 ms (females).
14. Moderate to severe hepatic impairment (Child-Pugh ≥ 7).
15. Insulin-dependent diabetes or oral hypoglycaemic agents with current hypoglycaemia risk requiring intervention.
16. Any physical/psychological/medication/lab finding at screening or baseline making patient unsuitable for study.
17. Allergy or intolerance to materials in either drug product.
18. Cognitive/neuropsychological exclusion if MoCA score < mean -1.5 SD adjusted for age/education.
19. Recent (2 weeks) change or planned change in antidepressant medication during intervention.

Company

Product

Legal

Psilocybin Therapy for Psychological Distress in Palliative Patients (PsyPal)

Detailed Description

Study Protocol

Preparation

Locations

Dosing

Integration

Therapeutic Protocol

Study Arms & Interventions

High-dose psilocybin

Interventions

Low-dose psilocybin

Interventions

Participants

Inclusion Criteria

Exclusion Criteria

Study Details

Study Team

Sponsors & Collaborators