Treatment Resistant DepressionPhase 2PsiDeRNCT04959253
Psilocybin in Depression Resistant to Standard Treatments
A Phase 2 study testing Psilocybin assisted therapy in people with Treatment Resistant Depression, run by King's College London at 1 site in United Kingdom.
Trial summary
A single centre clinical trial to evaluate the feasibility, safety and efficacy of psilocybin, given under supportive conditions, in a randomised, blinded design in adult participants with treatment resistant major depressive disorder. Read more about this study
- Who is it for?
- Ages 25 to 80 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Psilocybin assisted therapy
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 21 Jun 2021to 18 Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 25 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 25 - 80 years
- Fluent in the English language
- Fulfil Diagnostic and Statistical Manual of Mental Disorders (5th Edition) (DSM-5) criteria for a primary diagnosis of current single or recurrent episodes of MDD of at least moderate severity but without psychotic features as defined on the MINI 7.0. Positive and primary diagnoses on the MINI 7.0 will be subject to confirmation at clinical interview by a psychiatrist.
- 17-item HAM-D score ≥ 14.
- Have failed to respond to 2 or more antidepressants prescribed at the minimum effective dose for at least 6 weeks OR at least 1 antidepressant prescribed at the minimum effective dose for at least 6 weeks AND a course of evidence-based psychotherapy given for at least 6 sessions.
- For those aged ≥ 60 years, the first episode of depression must have started prior to their 60th birthday.
Who cannot join
- Diagnosis of bipolar disorder (defined as meeting DSM-5 criteria for bipolar 1 or bipolar 2) on the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
- Diagnosis of psychotic disorder (defined as meeting DSM-5 criteria for any psychotic disorder) on the MINI 7.0, EXCEPT substance/medication induced psychotic disorder where the duration was limited to the acute period of direct intoxication with the substance/medication. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
- Diagnosis of drug or alcohol dependence syndrome (defined as meeting DSM-5 criteria for any dependence syndrome) on the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
- Diagnosis of any personality disorder (defined as meeting DSM-5 criteria for any personality disorder) based on clinical interview and the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
- Diagnosis of any dementia (defined as meeting DSM-5 criteria for any dementia disorder) based on clinical interview by a psychiatrist.
- Personal history of a ≥ 1 suicide attempt in the past year requiring hospitalization, defined using the CSSRS (Q6 (past year) = "y") and clinical interview with a psychiatrist.
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- Other personal circumstances and behaviour judged to be incompatible with establishment of rapport or safe exposure to psilocybin.
- Depression secondary to other medical conditions
- Medical diagnosis incompatible with psilocybin treatment
- Inability to provide a screening blood sample, urine sample or electrocardiogram.
- Biochemical abnormalities (defined as falling outside the normal reference range) as evaluated by a full blood count, full biochemistry profile and thyroid function tests. Biochemical abnormalities must also be determined as clinically significant by a medical doctor to fulfil the criterion for exclusion.
- Electrocardiographic abnormalities, defined as any abnormality that is not normal sinus rhythm and determined as clinically significant by a medical doctor.
- Women of child bearing potential not using adequate contraception.
- Pregnant or breast-feeding women.
- Those unable to give informed consent.
- Non-registration with a GP or failure to consent to sharing of the GP summary care record and any psychiatric assessments held.
- Those enrolled in another drug trial
- Hypersensitivity to the IMP or to any of the excipients or placebo
- Exclusions for Pre-Existing Medical Conditions
- Participants will be excluded if they have a current diagnosis of ≥1 of:
- Uncontrolled diabetes
- Hypertension (defined as a systolic blood pressure ≥ 160mm/Hg or a diastolic blood pressure ≥ 100mm/Hg on three separate readings). All readings of systolic blood pressure ≥ 140mm/Hg or diastolic blood pressure ≥ 90mm/Hg will be reviewed by a clinician. Hypertension ascertained prior to dosing will be subject to clinical confirmation via collateral information from the GP or other source.
- Cardiac failure, defined as class IV of the New York Heart Association classification
- Renal failure, defined as ≥ stage 4 (GFR ≤ 29mL/min)
- Liver failure, defined as a clinical diagnosis of liver fibrosis, cirrhosis of the liver, liver failure or advanced liver disease.
- Any cardiac arrhythmia, except atrial fibrillation.
- Any form of epilepsy
- Past diagnosis of ≥1 of:
- Cerebrovascular accident or intracerebral trauma.
- Myocardial infarction within 1 year prior to the screening visit.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Clinical Research Facility, King's College Hospital
London, London, SE5 9RS
About this study
Official title: A Randomised, Placebo Controlled Trial of Psilocybin in Treatment Resistant Depression: A Feasibility Study
A single centre clinical trial to evaluate the feasibility, safety and efficacy of psilocybin, given under supportive conditions, in a randomised, blinded design in adult participants with treatment resistant major depressive disorder. The primary objective is to evaluate feasibility by measuring recruitment rates, dropout rates and by estimating the variance of the primary outcome measure (MADRS).
- Conditions
- Treatment Resistant Depression
- Being tested
- Psilocybin assisted therapy, Placebo assisted therapy
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Psilocybin assisted therapyCombination product
A package of psychological therapy and a single dosing session of psilocybin.
Placebo assisted therapyCombination product
A package of psychological therapy and a single dosing session of placebo.
| Study group | Role | What they receive |
|---|---|---|
| Psilocybin 25mg PO | Experimental | Not described Receives: Combination Product: Psilocybin assisted therapy |
| Placebo PO | Placebo comparator | Not described Receives: Combination Product: Placebo assisted therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recruitment rates
Recruitment rates to the trial
Measured: From opening to closing of trial recruitment period
Dropout rates
Dropout rates in the trial
Measured: From time of first enrollment until last participant last visit
Montgomery Asberg Depression Rating Scale (MADRS)
The variance in the MADRS between groups
Measured: 3 weeks from baseline
Secondary outcomes (3)
Montgomery Asberg Depression Rating Scale (MADRS)
The change in the Montgomery-Asberg Depression Rating Scale total score from the Baseline Visit (V2 - 1 day prior to treatment) to Week 3 after treatment (V6). Higher scores mean worse depression. Lowest score is 0. Highest score is 60.
Measured: 3 weeks from baseline
Montgomery Asberg Depression Rating Scale (MADRS)
The change in the Montgomery-Asberg Depression Rating Scale total score from the Baseline Visit (V2 - 1 day prior to treatment) to Week 3 after treatment (V6). Higher scores mean worse depression. Lowest score is 0. Highest score is 60.
Measured: 6 weeks from baseline
Time to event measures
Restart antidepressant medication for any reason, restart medication for continuing depressive symptoms or relapse from a previously recovered state (clinical judgement, supported by the QIDS-SR-16). Participants who withdraw from the study will be censored from the time to event analysis.
Measured: At any point from baseline (day 0) visit until 6-week follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2021
- Study start21 Jun 2021
- Primary completion18 Dec 2024
- Study completion18 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- More trials run by King's College LondonThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- King's College London
- Sponsor type
- University, hospital or other
- Collaborators
- South London and Maudsley NHS Foundation Trust
- Responsible party
- Sponsor
- Investigators
- James Rucker, MD PhD, Principal investigator, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04959253
- Sponsor's protocol ID
- 252750
- Acronym
- PsiDeR
- Status last verified
- Jun 2021
- First submitted
- 1 Jul 2021
- Last updated
- 28 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The Trial Management Group will consider data sharing on receipt of a distinct Statistical Analysis plan that is approved by the Trial Management Group.
Publications
Rucker J, Jafari H, Mantingh T, Bird C, Modlin NL, Knight G, Reinholdt F, Day C, Carter B, Young A. Psilocybin-assisted therapy for the treatment of resistant major depressive disorder (PsiDeR): protocol for a randomised, placebo-controlled feasibility trial. BMJ Open. 2021 Dec 1;11(12):e056091. doi: 10.1136/bmjopen-2021-056091.
PubMed 34853114
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Placebo Controlled Trial of Psilocybin in Treatment Resistant Depression: A Feasibility Study
- ClinicalTrials.gov ID
- NCT04959253
- Acronym / sponsor ID
- PsiDeR / 252750
- Conditions
- Treatment Resistant Depression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Collaborators
- South London and Maudsley NHS Foundation Trust
- Study start
- 21 Jun 2021 (actual)
- Primary completion
- 18 Dec 2024 (actual)
- Study completion
- 18 Dec 2024 (actual)
- First posted
- 13 Jul 2021 (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.
A single centre clinical trial to evaluate the feasibility, safety and efficacy of psilocybin, given under supportive conditions, in a randomised, blinded design in adult participants with treatment resistant major depressive disorder. The primary objective is to evaluate feasibility by measuring recruitment rates, dropout rates and by estimating the variance of the primary outcome measure (MADRS).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Psilocybin 25mg PO | Experimental | Combination Product: Psilocybin assisted therapy |
| Placebo PO | Placebo comparator | Combination Product: Placebo assisted therapy |
Who may qualify
- Ages
- 25 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 25 - 80 years
- Fluent in the English language
- Fulfil Diagnostic and Statistical Manual of Mental Disorders (5th Edition) (DSM-5) criteria for a primary diagnosis of current single or recurrent episodes of MDD of at least moderate severity but without psychotic features as defined on the MINI 7.0. Positive and primary diagnoses on the MINI 7.0 will be subject to confirmation at clinical interview by a psychiatrist.
- 17-item HAM-D score ≥ 14.
- Have failed to respond to 2 or more antidepressants prescribed at the minimum effective dose for at least 6 weeks OR at least 1 antidepressant prescribed at the minimum effective dose for at least 6 weeks AND a course of evidence-based psychotherapy given for at least 6 sessions.
Key exclusion criteria (30 listed)
- Diagnosis of bipolar disorder (defined as meeting DSM-5 criteria for bipolar 1 or bipolar 2) on the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
- Diagnosis of psychotic disorder (defined as meeting DSM-5 criteria for any psychotic disorder) on the MINI 7.0, EXCEPT substance/medication induced psychotic disorder where the duration was limited to the acute period of direct intoxication with the substance/medication. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
- Diagnosis of drug or alcohol dependence syndrome (defined as meeting DSM-5 criteria for any dependence syndrome) on the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
- Diagnosis of any personality disorder (defined as meeting DSM-5 criteria for any personality disorder) based on clinical interview and the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
- Diagnosis of any dementia (defined as meeting DSM-5 criteria for any dementia disorder) based on clinical interview by a psychiatrist.
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 assisted therapyA package of psychological therapy and a single dosing session of psilocybin. | Combination product | Psilocybin 25mg PO |
| Placebo assisted therapyA package of psychological therapy and a single dosing session of placebo. | Combination product | Placebo PO |
Primary outcome
Recruitment rates
Time frame: From opening to closing of trial recruitment period
Recruitment rates to the trial
Dropout rates
Time frame: From time of first enrollment until last participant last visit
Dropout rates in the trial
Montgomery Asberg Depression Rating Scale (MADRS)
Time frame: 3 weeks from baseline
The variance in the MADRS between groups
3 secondary outcomes
Montgomery Asberg Depression Rating Scale (MADRS)
Time frame: 3 weeks from baseline
Montgomery Asberg Depression Rating Scale (MADRS)
Time frame: 6 weeks from baseline
Time to event measures
Time frame: At any point from baseline (day 0) visit until 6-week follow-up
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2026.
- Derived from this study: PubMed 34853114Rucker J, Jafari H, Mantingh T, Bird C, Modlin NL, Knight G, Reinholdt F, Day C, Carter B, Young A. Psilocybin-assisted therapy for the treatment of resistant major depressive disorder (PsiDeR): protocol for a randomised, placebo-controlled feasibility trial. BMJ Open. 2021 Dec 1;11(12):e056091. doi: 10.1136/bmjopen-2021-056091.
- Individual participant dataSharing planned: No. The Trial Management Group will consider data sharing on receipt of a distinct Statistical Analysis plan that is approved by the Trial Management Group.
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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. This study is not recruiting at the moment.
James Rucker, MD PhD principal investigator
King's College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Psilocybin assisted therapy in people with Treatment Resistant Depression, run by King's College London at 1 site in United Kingdom.
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 6 inclusion and 30 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: finished, as of the sponsor's last update on 28 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recruitment rates (time frame: From opening to closing of trial recruitment period). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04959253, which also lists 1 linked publication.
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 28 Aug 2026.