The Safety and Efficacy of Psilocybin Therapy Compared to Low-dose Control in Reducing Depressive Symptoms in Patients With COPD, ALS, MS, or APD.
The goal of this clinical trial is to evaluate whether psilocybin therapy can effectively treat depression and psychological distress in adult patients with COPD, ALS, MS, or APD who have at least 6 months life expectancy. The main questions it aims to answer are: * Can psilocybin therapy safely reduce depressive symptoms compared to low-dose control? * Will the therapeutic effects be rapid and sustained over a 6-month period? Researchers will compare patients receiving two escalating doses of psilocybin (15mg followed by 25mg) against those receiving two low doses (1mg) to see if the higher doses lead to greater improvements in depression, anxiety, demoralization, and quality of life. Participants will: * Attend three preparation sessions with psychotherapists (1-2 hours each) * Undergo two supervised psilocybin dosing sessions (6-8 hours each) * Complete five integration therapy sessions following the dosing sessions * Participate in follow-up assessments at 6 weeks, 3 months, and 6 months * Have access to a digital care platform and peer support groups during the 6-month follow-up period * Optional: Control group participants may receive one high-dose psilocybin session (25mg) after the initial study period
• 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
• Patient meets ICD-10 criteria for major depressive disorder documented through the com-pletion of the mood section of the Mini International Neuropsychiatric Interview by a screen-ing psychologist or physician.
• Patient has a MADRS score of \> 19.
• Patient should have a life expectancy of at least 6 months (assessed by study physician).
• Patient is at least 18 years of age.
• Patient has an identified caregiver/support person. See specific conditions for Czechia in Appendix 5.
• Patient is able to read and understand the informed consent and all scales used in a local language. For those with ALS, MS, or APD, competency is ensured via neurologist assessment, cognitive screening, caregiver support during screening and interactive approaches where the screening clinician ask the patient to explain their understanding of consent elements, re-explaining potentially misunderstood information.
• Patient is able to and willing to adhere to study requirements, including attending all study visits, preparatory and follow-up sessions, and completing all study evaluations.
• Patient is able to ingest capsules.