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
Who can participate
Age range
18 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Patient has to be diagnosed with one of the following four conditions, defined as:
. 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.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Depressive symptoms (MADRS)
Timeframe: Baseline (Day -14) to Primary Endpoint (Day 56)
. 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.
Exclusion criteria
. Patient has used a psychedelic substance in the past 6 months (e.g., psilocybin, LSD, 5-MeO-DMT, DMT, ayahuasca or mescaline).
. Patient is in active treatments for other psychiatric disorders, judged by the screening clinician to be a more significant clinical problem than depression / distress.
. Patient meets ICD-10 criteria for schizophrenia spectrum or other psychotic disorders, including major depressive disorder with psychotic features (except substance/medication-induced or due to another medical condition) or bipolar I/II disorder.
. Patients with any lifetime diagnosis of schizophrenia spectrum or other psychotic disorders.
. Patient has a first-degree relative with schizophrenia spectrum, bipolar I disorder or other psychotic disorders (expect substance/medication-induced or due to another medical condition).
. Patients with a pre-existing psychiatric condition judged to be incompatible with safe exposure to psilocybin therapy.
. Significant suicide risk as defined by (1) suicidal ideation with intent to act (defined as ≥ 5 on MADRS item 10), (2) suicidal attempts within the past year, or (3) clinical assessment of significant suicidal risk during patient interview.
. Patient meets ICD-10 criteria for active/current alcohol or drug use disorder.