COPD (Chronic Obstructive Pulmonary Disease)Phase 2PsyPalNCT06782724
Psilocybin Therapy for Psychological Distress in Palliative Patients
A Phase 2 study testing Psilocybin therapy in people with COPD (Chronic Obstructive Pulmonary Disease) and ALS (Amyotrophic Lateral Sclerosis), run by University Medical Center Groningen at 4 sites in 4 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COPD (Chronic Obstructive Pulmonary Disease), ALS (Amyotrophic Lateral Sclerosis), MS (Multiple Sclerosis)
- What is being tested?
- Psilocybin therapy
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 108 participants
- Where
- 4 sitesin 4 countries
- Study dates
- 1 Jul 2025to 1 Jan 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- Patient has ongoing treatment with antipsychotic drugs. Any prohibited agents must have been stopped at least 5x the elimination half-life of the specific drug at the time of baseline (see Appendix 1a for Prohibited medications).
- Patient is unwilling or unable to pause formal psychotherapy (days 0-42).
- Patient has neurological conditions (e.g., intracranial tumour, epilepsy, brain injuries, or other neurological disorders) expected by the PIs to conflict with the treatment / study protocol.
- Disease-specific exclusion criteria:
- COPD: Unresolved exacerbation or pulmonary infection within last 4 weeks. ALS: Significant cognitive deficits (MoCa, see below). MS: Significant cognitive deficits (MoCa, see below), epilepsy or radiologically isolated syndrome.
- APD: Dementia (MoCa, see below), or Schwab and England ADL scale with scores > 80% in the best functional state.
- Cardiovascular conditions: recent stroke (< 1 year from signing of ICF), recent myocardial infarction (< 1 year from signing of ICF), uncontrolled hypertension (blood pressure > 140/90 mmHg), clinically significant arrhythmia within 1 year of signing the ICF, or QTc prolongation exceeding 450ms (males) / 470ms (females).
- Patient has moderate to severe hepatic impairment (Child-Pugh score ≥ 7).
- Patient has insulin-dependent diabetes or who are taking oral hypoglycaemic agents and have a current risk of hypoglycaemia that would require medical intervention.
- Patient has any physical or psychological symptoms, medications, blood test results or clinically significant findings at Screening or Baseline (based on the clinical judgement of clinical/medical study personnel) that would make a patient unsuitable for the study.
- Patient has an allergy or intolerance to any of the materials contained in either drug product.
- Cognitive and Neuropsychological assessment: Patients will be excluded if they score below mean minus 1.5 Standard Deviation according to normative age and scholarity adjusted data on the Montreal Cognitive Assessment (MoCA) assessment.
- Recent (2 weeks) change or planned change in antidepressant medication during the intervention.
- Women who are pregnant, intend to become pregnant during the study or who are currently nursing, or are unwilling to use Highly Effective Contraceptive Methods
Trial locations and contacts
4 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
4 sites in 4 countries
Czechia1 site, 1 recruiting
- Recruiting
National Institute of Mental Health
Prague
Tomas Palenicek, tomas.palenicek@nudz.cz
Tomas Palenicek
Denmark1 site, 1 recruiting
- Recruiting
Bispebjerg Hospital
Copenhagen
Kirsten Svenstrup, kirsten.svenstrup@regionh.dk
Kirsten Svenstrup
Netherlands1 site, 1 recruiting
- Recruiting
University Medical Center Groningen
Groningen, Provincie Groningen
Robert Schoevers, r.a.schoevers@umcg.nl
Sanne Smith-Apeldoorn
Portugal1 site, 1 recruiting
- Recruiting
Champalimaud Foundation
Lisbon
Albino Oliveira-Maia, albino.maia@neuro.fchampalimaud.org
Albino Oliveira-Maia
About this study
Official title: 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?
Read more
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
Read the detailed description
Rationale Patients with chronic obstructive pulmonary disorder (COPD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), or atypical and advanced Parkinsonian disorder (APD) often suffer from severe psychological distress with demoralization and death anxiety, which may culminate in to depressive disorder. Treatments of depression in palliative care currently involves psychotherapy and/or the use of antidepressants. However, these treatments have shown limited efficacy which urgently calls for new and innovative approaches. In recent years, a number of studies have shown very promising results of psilocybin therapy in alleviating psychological distress in patients with advanced cancer. The current study (PsyPal) aims to evaluate whether psilocybin therapy can also lead to rapid and sustained decreases in depressive symptoms, demoralization and other facets of psychological distress in patients who suffer from COPD, ALS, MS and APD.
Objective The primary objective of the PsyPal study is to assess the safety and efficacy of psilocybin therapy compared to low-dose control in reducing depressive symptoms in patients with COPD, ALS, MS, or APD. Secondary objectives of PsyPal are to assess change in clinical functioning, end-of-life anxiety, psychological/existential distress, health-related quality of life, and how it impacts caregiver 's health- and economic burden. The safety objective of PsyPal is to evaluate the difference in adverse events between high and low dose groups before, during and after the dosing session. Exploratory objectives include the investigation of psychological mechanism, subjective effects, biomarkers (EEG and blood-based), cost-effectiveness, and the usefulness of a digital care platform, with a mixed methods approach.
Main trial endpoints The main trial endpoint for PsyPal is the change in depression severity from baseline to 6 weeks after the second dose of psilocybin (high dose session). Adverse events and change in depression symptoms will also be assessed at 3- and 6-month follow-up to determine the safety and sustained effects of psilocybin therapy.
Secondary trial endpoints Secondary trial endpoints will be assessed at baseline and 6 weeks after the second dose of psilocybin. These include response rate, anxiety, demoralization, health-related quality of life, experiential avoidance, coping with illness, death anxiety, the wish to hasten death, self-compassion, spirituality, attachment, pain, healthcare resource use, blood-based biomarkers, and functional brain changes. Some secondary endpoints will also be assessed at the 3- and 6-month follow-up, including anxiety, demoralization, health-related quality of life, experiential avoidance, and coping with illness. These endpoints aim to improve our understanding of the effects of psilocybin therapy, how psilocybin therapy works, and to see which patients show the best response. Finally, changes in (religious/spiritual) beliefs/understandings and the experience(s) with psilocybin therapy will be assessed through in-depth qualitative interviews with patients that are conducted 6 weeks after the second dose of psilocybin.
Trial design PsyPal trial consists of a double-blind randomized low-dose controlled clinical trial with long term follow-up. Patients who are enrolled in the trial will be actively participating for ten weeks. After the primary endpoint, patients who received a low dose of psilocybin (1 mg) will be offered an optional single open label high-dose of psilocybin (25mg) together with three integration sessions. During long-term follow-up, patients will have access to a digital care platform and peer support groups.
Trial population The trial population in PsyPal consists of patients with COPD, ALS, MS, or APD and co-morbid depression. The main further inclusion criteria for participation are an age of 18 or higher, having an identified caregiver or support person, and a life expectancy of at least 6 months. The main exclusion criteria are current use of antipsychotic drugs, suicidal ideations, schizophrenia or other psychotic disorders, bipolar I/II disorder, other major neurological conditions, cardiovascular conditions, diabetes, and/or moderate to severe hepatic impairment (i.e., liver failure). Other exclusion criteria are a first-degree relative on the schizophrenia spectrum, other psychotic disorders, or bipolar I disorder.
Interventions
Patients will receive psilocybin therapy consisting of three phases; 1) preparation, 2) dosing, and 3) integration:
Preparation - The preparation phase consists of three psychotherapy sessions of 1-2 hours each. The purpose of these sessions is threefold: to build a therapeutic alliance between the patient and the therapist, to make a psychotherapeutic treatment plan for the patient using a process-based approach, and to educate patients about psilocybin's acute effects and how patients and therapists together can handle difficult experiences during the dosing sessions.
Dosing - The dosing phase of PsyPal starts 1-3 days after the last preparation session. It consists of two escalating dosing sessions of 6-8 hours each. The patient first receives a moderate dose of psilocybin (15mg). Two weeks later, the patient receives a high dose of psilocybin (25mg). Patients in the control group will receive two doses of psilocybin (1mg). All dosing sessions take place under supervision of two trained therapists within a treatment room specifically designed for psilocybin therapy and with a medical doctor on call.
Integration - The integration phase consists of five psychotherapeutic sessions of 1-2 hours each. There are two integration sessions following the first dosing session and three integration sessions following the second dosing session. The integration sessions are intended for further psychotherapeutic work, including working with the experience(s) that may have emerged during dosing sessions, and clinical assessment of the patient. Central topics may include the relationship with their life-limiting illness, death, meaning, sense of purpose, personal (religious/spiritual) beliefs, (social) relationships, and conflict resolution. The patient can also share thoughts and feelings about the PsyPal trial.
Long-term follow-up After the intervention, patients will be returned to regular care and followed for a period of 6 months, tracking usage of healthcare resources, the digital care platform, and peer support groups. Qualitative aspects of the intervention will be evaluated for patients, caregivers and therapists. Long-term safety data of psilocybin therapy will be collected for the four patient populations.
- Conditions
- COPD (Chronic Obstructive Pulmonary Disease), ALS (Amyotrophic Lateral Sclerosis), MS (Multiple Sclerosis), Major Depressive Disorder (MDD), Atypical Parkinson Disease
- Being tested
- Psilocybin therapy
- Keywords
- psilocybin, therapy, palliative, care, palliative care, end-of-life distress, depression, psychological distress, psypal, copd, als, ms, apd, chronic obstructive pulmonary disorder, amyotrophic lateral sclerosis, multiple sclerosis, major depressive disorder, atypical parkinson disease, existential distress
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Depressive Disorder, Major, Parkinson Disease, Familial, Type 1, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Psilocybin therapyDrug
Psilocybin therapy consisting of three preparation, two dosing, and three integration sessions. All sessions will take place in a controlled, safety environment and supported by two study therapists
| Study group | Role | What they receive |
|---|---|---|
| Moderate (15mg) and high dose (25mg) psilocybin group | Experimental | Patients assigned to this arm will first receive three prepration sessions followed by one moderate dose (15mg) of psilocybin. Patients will then receive two integration sessions and a high dose (25mg) of psilocybin. This is followed by three integration sessions. Receives: Drug: Psilocybin therapy |
| Low-dose (1mg) psilocybin group | Placebo comparator | Patients assigned to this arm will first receive three prepration sessions followed by one low dose (1mg) of psilocybin. Patients will then receive two integration sessions and another low dose (1mg) of psilocybin. This is followed by three integration sessions. Receives: Drug: Psilocybin therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Depressive symptoms (MADRS)
To examine medium/high-dose psilocybin therapy safety and efficacy in reducing symptoms of depression in patients with COPD, ALS, MS, or APD, compared to the low-dose control group.
Measured: Baseline (Day -14) to Primary Endpoint (Day 56)
Secondary outcomes (15)
Response rate
To determine the response rate to psilocybin therapy (≥50% reduction in MADRS)
Measured: Baseline (Day -14) to Primary Endpoint (Day 56)
End-of-life anxiety
To evaluate the effect of psilocybin therapy on end-of-life anxiety
- Death and Dying Distress Scale (DADDS)
Measured: Baseline (Day -14) to Primary Endpoint (Day 56)
Anxiety and depression (symptoms)
To evaluate the effect of psilocybin therapy on symptoms of anxiety and depression
- Hospital Anxiety and Depression Scale (HADS)
Measured: Baseline (Day -14) to Primary Endpoint (Day 56)
Demoralization
To assess the impact of psilocybin therapy on demoralization
- Demoralization Scale-II (DS-II)
Measured: Baseline (Day -14) to Primary Endpoint (Day 56)
Impact on Quality of life
To evaluate the effect of psilocybin therapy on quality of life
- EQ-5D-5L
Measured: Baseline (Day -14) to Primary Endpoint (Day 56)
Caregiver burden
To assess the impact of psilocybin therapy on caregiver burden
- Zarit Burden Interview (ZBI-7)
Measured: Baseline (Day -14) to Primary Endpoint (Day 56)
Daily functioning in COPD
To assess the impact of psilocybin therapy on daily function in patients with COPD.
- CODP Assessment Test (CAT)
Measured: Baseline (Day -14) to Primary Endpoint (Day 56)
Health-related quality of life in COPD
To assess the impact of psilocybin therapy on health-related quality of life in patients with COPD.
- St. George's Respiratory Questionnaire (SGRQ-C)
Measured: Baseline (Day -14) to Primary Endpoint (Day 56)
Health-related quality of life in ALS
To assess the impact of psilocybin therapy on quality of life in patients with ALS.
- Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALS-AQ-5)
Measured: Baseline (Day -14) to Primary Endpoint (Day 56)
Functional status in ALS
To assess the impact of psilocybin therapy on functional status in patients with ALS
- ALS Functional Rating Scale Revised (ALS-FRS-R)
Measured: Baseline (Day -14) to Primary Endpoint (Day 56)
Health-related quality of life in MS
To assess the impact of psilocybin therapy on health-related quality of life in patients with MS.
- Expanded Disability Status Scale (EDSS)
Measured: Baseline (Day -14) to Primary Endpoint (Day 56)
Health-related quality of life in APD
To assess the impact of psilocybin therapy on health-related quality of life in patients with APD.
- Parkinson's Disease Questionnaire (PDQ-8)
Measured: Baseline (Day -14) to Primary Endpoint (Day 56)
Motor and non-motor symptoms in APD
To assess the impact of psilocybin therapy on (non-)motor symptoms in patients with APD.
- Movement Disorders Society Unified Parkinson Disease Rating Scale (MDS-UPDRS, parts I, II, and III)
Measured: Baseline (Day -14) to Primary Endpoint (Day 56)
Functional magnetic resonance imaging (fMRI) in APD
At the Champalimaud Foundation in Lisbon, structural and functional magnetic resonance imaging (MRI) will be conducted in patients with APD. Changes in brain volume and tissue microstructures (with fractional anisotropy and diffusivity) will be computed. Changes in whole brain resting-state functional connectivity will be additionally computed using the BOLD response. The structural and function MRI protocol consists of 3D T1-weighted, T2/PD-weighted, FLAIR, T2*, diffusion tensor, and blood-oxygen-level-dependent (BOLD) imaging.
Measured: Baseline (Day -14) to one week after Dose 2 (Day 21)
Incidence, severity, and frequency of (serious) adverse events following psilocybin therapy
The reporting of (serious) adverse events by using MedDRA version 27.0 during the clinical trial.
Measured: Baseline (Day -14), Dose 1 (Day 0), Integration 1 (Day 1), Integration 2 (Day 7), Dose 2 (Day 14), Integration 3 (Day 15), Integration 4 (Day 21), Integration 5 (Day 28), Primary endpoint (Day 56), Open label dose (Day 62), 3- and 6-month follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2025
- Study start1 Jul 2025
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COPD (Chronic Obstructive Pulmonary Disease)Studies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized double-blind low-dose controlled clinical trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 108 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- HumanKindLabs, University of Copenhagen, CTC Clinical Trial Consultants AB, OPEN Foundation, IESE Business School, Uppsala University, The Champalimaud Centre, Lisbon, Portugal, Stockholm University, University of Groningen, The Netherlands, National Institute of Mental Health, Czech Republic, European Association for Palliative Care, Madopa, Bispebjerg Hospital, European Association of Neurological Associations (EFNA), 29k International AB, Lung Alliance Netherlands, European Psychiatric Association, Norrsken Mind
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06782724
- Sponsor's protocol ID
- 18870
- Other IDs
- 2023-510488-36-01, 2023
- Acronym
- PsyPal
- Status last verified
- Apr 2026
- First submitted
- 2 Jan 2025
- Last updated
- 8 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety and Efficacy of Psilocybin Therapy Compared to Low-dose Control in Reducing Depressive Symptoms in Patients With COPD, ALS, MS, or APD.
- ClinicalTrials.gov ID
- NCT06782724
- Acronym / sponsor ID
- PsyPal / 18870
- Conditions
- COPD (Chronic Obstructive Pulmonary Disease), ALS (Amyotrophic Lateral Sclerosis), MS (Multiple Sclerosis), Major Depressive Disorder (MDD), Atypical Parkinson Disease
- Keywords
- psilocybin, therapy, palliative, care, palliative care, end-of-life distress, depression, psychological distress
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 108 participants (estimated)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- HumanKindLabs, University of Copenhagen, CTC Clinical Trial Consultants AB, OPEN Foundation, IESE Business School, Uppsala University, The Champalimaud Centre, Lisbon, Portugal, Stockholm University, University of Groningen, The Netherlands, National Institute of Mental Health, Czech Republic, European Association for Palliative Care, Madopa, Bispebjerg Hospital, European Association of Neurological Associations (EFNA), 29k International AB, Lung Alliance Netherlands, European Psychiatric Association, Norrsken Mind
- Study start
- 1 Jul 2025 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 20 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Rationale Patients with chronic obstructive pulmonary disorder (COPD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), or atypical and advanced Parkinsonian disorder (APD) often suffer from severe psychological distress with demoralization and death anxiety, which may culminate in to depressive disorder. Treatments of depression in palliative care currently involves psychotherapy and/or the use of antidepressants. However, these treatments have shown limited efficacy which urgently calls for new and innovative approaches. In recent years, a number of studies have shown very promising results of psilocybin therapy in alleviating psychological distress in patients with advanced cancer. The current study (PsyPal) aims to evaluate whether psilocybin therapy can also lead to rapid and sustained decreases in depressive symptoms, demoralization and other facets of psychological distress in patients who suffer from COPD, ALS, MS and APD.
Objective The primary objective of the PsyPal study is to assess the safety and efficacy of psilocybin therapy compared to low-dose control in reducing depressive symptoms in patients with COPD, ALS, MS, or APD. Secondary objectives of PsyPal are to assess change in clinical functioning, end-of-life anxiety, psychological/existential distress, health-related quality of life, and how it impacts caregiver 's health- and economic burden. The safety objective of PsyPal is to evaluate the difference in adverse events between high and low dose groups before, during and after the dosing session. Exploratory objectives include the investigation of psychological mechanism, subjective effects, biomarkers (EEG and blood-based), cost-effectiveness, and the usefulness of a digital care platform, with a mixed methods approach.
Main trial endpoints The main trial endpoint for PsyPal is the change in depression severity from baseline to 6 weeks after the second dose of psilocybin (high dose session). Adverse events and change in depression symptoms will also be assessed at 3- and 6-month follow-up to determine the safety and sustained effects of psilocybin therapy.
Secondary trial endpoints Secondary trial endpoints will be assessed at baseline and 6 weeks after the second dose of psilocybin. These include response rate, anxiety, demoralization, health-related quality of life, experiential avoidance, coping with illness, death anxiety, the wish to hasten death, self-compassion, spirituality, attachment, pain, healthcare resource use, blood-based biomarkers, and functional brain changes. Some secondary endpoints will also be assessed at the 3- and 6-month follow-up, including anxiety, demoralization, health-related quality of life, experiential avoidance, and coping with illness. These endpoints aim to improve our understanding of the effects of psilocybin therapy, how psilocybin therapy works, and to see which patients show the best response. Finally, changes in (religious/spiritual) beliefs/understandings and the experience(s) with psilocybin therapy will be assessed through in-depth qualitative interviews with patients that are conducted 6 weeks after the second dose of psilocybin.
Trial design PsyPal trial consists of a double-blind randomized low-dose controlled clinical trial with long term follow-up. Patients who are enrolled in the trial will be actively participating for ten weeks. After the primary endpoint, patients who received a low dose of psilocybin (1 mg) will be offered an optional single open label high-dose of psilocybin (25mg) together with three integration sessions. During long-term follow-up, patients will have access to a digital care platform and peer support groups.
Trial population The trial population in PsyPal consists of patients with COPD, ALS, MS, or APD and co-morbid depression. The main further inclusion criteria for participation are an age of 18 or higher, having an identified caregiver or support person, and a life expectancy of at least 6 months. The main exclusion criteria are current use of antipsychotic drugs, suicidal ideations, schizophrenia or other psychotic disorders, bipolar I/II disorder, other major neurological conditions, cardiovascular conditions, diabetes, and/or moderate to severe hepatic impairment (i.e., liver failure). Other exclusion criteria are a first-degree relative on the schizophrenia spectrum, other psychotic disorders, or bipolar I disorder.
Interventions
Patients will receive psilocybin therapy consisting of three phases; 1) preparation, 2) dosing, and 3) integration:
Preparation - The preparation phase consists of three psychotherapy sessions of 1-2 hours each. The purpose of these sessions is threefold: to build a therapeutic alliance between the patient and the therapist, to make a psychotherapeutic treatment plan for the patient using a process-based approach, and to educate patients about psilocybin's acute effects and how patients and therapists together can handle difficult experiences during the dosing sessions.
Dosing - The dosing phase of PsyPal starts 1-3 days after the last preparation session. It consists of two escalating dosing sessions of 6-8 hours each. The patient first receives a moderate dose of psilocybin (15mg). Two weeks later, the patient receives a high dose of psilocybin (25mg). Patients in the control group will receive two doses of psilocybin (1mg). All dosing sessions take place under supervision of two trained therapists within a treatment room specifically designed for psilocybin therapy and with a medical doctor on call.
Integration - The integration phase consists of five psychotherapeutic sessions of 1-2 hours each. There are two integration sessions following the first dosing session and three integration sessions following the second dosing session. The integration sessions are intended for further psychotherapeutic work, including working with the experience(s) that may have emerged during dosing sessions, and clinical assessment of the patient. Central topics may include the relationship with their life-limiting illness, death, meaning, sense of purpose, personal (religious/spiritual) beliefs, (social) relationships, and conflict resolution. The patient can also share thoughts and feelings about the PsyPal trial.
Long-term follow-up After the intervention, patients will be returned to regular care and followed for a period of 6 months, tracking usage of healthcare resources, the digital care platform, and peer support groups. Qualitative aspects of the intervention will be evaluated for patients, caregivers and therapists. Long-term safety data of psilocybin therapy will be collected for the four patient populations.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- randomized double-blind low-dose controlled clinical trial
| Arm | Type | Receives |
|---|---|---|
| Moderate (15mg) and high dose (25mg) psilocybin group | Experimental | Drug: Psilocybin therapyPatients assigned to this arm will first receive three prepration sessions followed by one moderate dose (15mg) of psilocybin. Patients will then receive two integration sessions and a high dose (25mg) of psilocybin. This is followed by three integration sessions. |
| Low-dose (1mg) psilocybin group | Placebo comparator | Drug: Psilocybin therapyPatients assigned to this arm will first receive three prepration sessions followed by one low dose (1mg) of psilocybin. Patients will then receive two integration sessions and another low dose (1mg) of psilocybin. This is followed by three integration sessions. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (22 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Psilocybin therapyPsilocybin therapy consisting of three preparation, two dosing, and three integration sessions. All sessions will take place in a controlled, safety environment and supported by two study therapists | Drug | Low-dose (1mg) psilocybin group, Moderate (15mg) and high dose (25mg) psilocybin group |
Primary outcome
Depressive symptoms (MADRS)
Time frame: Baseline (Day -14) to Primary Endpoint (Day 56)
To examine medium/high-dose psilocybin therapy safety and efficacy in reducing symptoms of depression in patients with COPD, ALS, MS, or APD, compared to the low-dose control group.
15 secondary outcomes
Response rate
Time frame: Baseline (Day -14) to Primary Endpoint (Day 56)
End-of-life anxiety
Time frame: Baseline (Day -14) to Primary Endpoint (Day 56)
Anxiety and depression (symptoms)
Time frame: Baseline (Day -14) to Primary Endpoint (Day 56)
Demoralization
Time frame: Baseline (Day -14) to Primary Endpoint (Day 56)
Impact on Quality of life
Time frame: Baseline (Day -14) to Primary Endpoint (Day 56)
Caregiver burden
Time frame: Baseline (Day -14) to Primary Endpoint (Day 56)
Daily functioning in COPD
Time frame: Baseline (Day -14) to Primary Endpoint (Day 56)
Health-related quality of life in COPD
Time frame: Baseline (Day -14) to Primary Endpoint (Day 56)
Health-related quality of life in ALS
Time frame: Baseline (Day -14) to Primary Endpoint (Day 56)
Functional status in ALS
Time frame: Baseline (Day -14) to Primary Endpoint (Day 56)
Health-related quality of life in MS
Time frame: Baseline (Day -14) to Primary Endpoint (Day 56)
Health-related quality of life in APD
Time frame: Baseline (Day -14) to Primary Endpoint (Day 56)
Motor and non-motor symptoms in APD
Time frame: Baseline (Day -14) to Primary Endpoint (Day 56)
Functional magnetic resonance imaging (fMRI) in APD
Time frame: Baseline (Day -14) to one week after Dose 2 (Day 21)
Incidence, severity, and frequency of (serious) adverse events following psilocybin therapy
Time frame: Baseline (Day -14), Dose 1 (Day 0), Integration 1 (Day 1), Integration 2 (Day 7), Dose 2 (Day 14), Integration 3 (Day 15), Integration 4 (Day 21), Integration 5 (Day 28), Primary endpoint (Day 56), Open label dose (Day 62), 3- and 6-month follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2026.
- Official website for PsyPalLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Psilocybin therapy in people with COPD (Chronic Obstructive Pulmonary Disease) and ALS (Amyotrophic Lateral Sclerosis), run by University Medical Center Groningen at 4 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Czechia, Denmark, Netherlands, Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Robert A Schoevers, Professor (050 361 2008, r.a.schoevers@umcg.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Depressive symptoms (MADRS) (time frame: Baseline (Day -14) to Primary Endpoint (Day 56)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2026.