Depression - Major Depressive DisorderNCT07164755
Measurement of Serum Inflammatory Markers in Patients Treatment-resistant Depression Given Psilocybin
An observational study of Depression - Major Depressive Disorder, run by King's College London at 1 site in United Kingdom.
Trial summary
About one in three people with major depression respond poorly to standard antidepressant treatments. This kind of depression is called treatment-resistant depression, and it can lead to long-term disability, financial challenges, and a higher risk of suicide. Read more about this study
- Who is it for?
- Ages 25 to 80 years
- Conditions the study is for
- Depression - Major Depressive Disorder
- How many people
- 46 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 21 Jun 2021to Sep 2026
- Phase
- Observational
- 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 25 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with treatment-resistant depression, recruited in the UK
Who may be able to join
- Fluent in the English language
- Fulfil Diagnostic and Statistical Manual of Mental Disorders (5th Edition) (DSM-5) criteria for current single or recurrent episodes of MDD of at least moderate severity but without psychotic features, as defined on the MINI 7.0.
- 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 confirmation at 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
King's College London Institute of Psychiatry, Psychology and Neuroscience
London, SE5 8AF
About this study
Official title: Measurement of Serum Cytokine Levels in Samples Collected as Part of a Clinical Trial of Psilocybin for Treatment-resistant Depression.
About one in three people with major depression respond poorly to standard antidepressant treatments. This kind of depression is called treatment-resistant depression, and it can lead to long-term disability, financial challenges, and a higher risk of suicide.
Psilocybin-a compound found in certain mushrooms-has shown early promise as a new treatment for this difficult-to-treat depression. Scientists believe it works by affecting a specific brain receptor (called 5-HT2A), which helps the brain become more flexible and adaptable. But there's another possible mechanism of psilocybin that hasn't been studied much: its ability to influence the immune system.
Read more
Recent research suggests that inflammation in the body might play a role in depression, especially when treatments don't work. High levels of certain inflammatory markers (called cytokines) are linked to poor response to antidepressants, while lower levels are tied to feeling better. Psilocybin may help reduce this inflammation, which could be part of why it helps some people feel better.
Still, we don't fully understand how a person's inflammation levels before treatment, and how those levels change afterward, relate to how well psilocybin works. Figuring this out could help doctors better match patients to psychedelic therapy and discover new ways to treat depression.
In this study, blood samples from a recent study (called the PsiDeR trial) that tested psilocybin in people with treatment-resistant depression will be analyzed. Cytokine levels in these blood samples, as well as levels of another type of molecule linked to inflammation, called mRNA, will be measured.
Read the detailed description
Chronic and elevated inflammation is associated with depression. Depressed patients tend to have raised inflammatory markers compared to healthy controls, and studies have reported that the greatest elevation is seen in patients with treatment-resistant depression (TRD). Previous studies highlight the bidirectional relationship between inflammation and depression. Elevated pro-inflammatory cytokines are linked to poor antidepressant response, while reductions in these markers are associated with symptom improvement. While neuroinflammation may play a role in the pathophysiology of depression, inflammation is also a causal risk factor for physical illnesses that are often co-morbid with depression, such as cardiovascular disease. As such, targeting inflammation in patients with depression may have significant implications for both their mental and physical health.
Psychedelics are emerging as a potential new class of therapeutic agents for psychiatric illness, including depression. It has been suggested that their therapeutic effect may partly be due to reducing inflammation. Psychedelics have been shown reduce markers of inflammation in models of human inflammatory disease, both in vitro and in vivo. While, as might be expected, psilocybin was not found to reduce markers of inflammation in healthy human volunteers, in a clinical sample of people with treatment-resistant depression, use of ayahuasca (containing the psychedelic N,N DMT) resulted in a significant reduction in CRP levels compared to participants given placebo, with the reduction in CRP levels significantly correlated with a reduction in depressive symptoms. Ayahuasca consists of an admixture of multiple different compounds. As such, the relative contribution of the psychedelic to the anti-inflammatory effect that was observed is unknown.
The effect of isolated psychedelic compounds such as psilocybin on the systemic inflammatory state of patients, specifically patients with depression, therefore, remains to be investigated. Psilocybin's capacity to reduce inflammation, as evidenced in preclinical models, may be a crucial mechanism underlying its therapeutic effects. Moreover, while it is recognised that baseline inflammation levels can influence the effectiveness of conventional antidepressants, it is unclear whether this is also the case for psilocybin.
This study aims to evaluate serum cytokine and inflammatory-related mRNA levels in samples collected from participants with TRD who took part in the (Psi)locybin in (De)pression (R)esistant to Standard Treatments (PsiDeR) Trial, and the relationships between these and psilocybin treatment response. PsiDeR was a randomised, placebo-controlled trial of psilocybin as a treatment for TRD that has now completed.
- Conditions
- Depression - Major Depressive Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Psilocybin-treated group blood samples | Blood samples from participants in Psider trial treated with psilocybin 25mg | |
| Placebo-treated group blood samples | Blood samples from participants in Psider trial treated with placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Linear regression to examine the association between baseline cytokines and depression outcomes at six weeks
Linear regression to examine the association between baseline cytokines and depression outcomes at six weeks
Measured: Six weeks
Secondary outcomes (1)
Linear regression to examine the association between cytokine level change and depression outcomes at six weeks.
Linear regression to examine the association between cytokine level change and depression outcomes at six weeks.
Measured: Six weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2025
- Study start21 Jun 2021
- Primary completionSep 2026 (estimated)
- Study completionSep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Depression - Major Depressive DisorderStudies 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
- Observational
- Observational model
- Other
- Time perspective
- Retrospective
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- King's College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07164755
- Sponsor's protocol ID
- 357453
- Status last verified
- Sep 2025
- First submitted
- 2 Sep 2025
- Last updated
- 10 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Measurement of Serum Cytokine Levels in Samples Collected as Part of a Clinical Trial of Psilocybin for Treatment-resistant Depression.
- ClinicalTrials.gov ID
- NCT07164755
- Acronym / sponsor ID
- 357453
- Conditions
- Depression - Major Depressive Disorder
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 46 participants (actual)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Study start
- 21 Jun 2021 (actual)
- Primary completion
- Sep 2026 (estimated)
- Study completion
- Sep 2026 (estimated)
- First posted
- 10 Sep 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.
About one in three people with major depression respond poorly to standard antidepressant treatments. This kind of depression is called treatment-resistant depression, and it can lead to long-term disability, financial challenges, and a higher risk of suicide.
Psilocybin-a compound found in certain mushrooms-has shown early promise as a new treatment for this difficult-to-treat depression. Scientists believe it works by affecting a specific brain receptor (called 5-HT2A), which helps the brain become more flexible and adaptable. But there's another possible mechanism of psilocybin that hasn't been studied much: its ability to influence the immune system.
Recent research suggests that inflammation in the body might play a role in depression, especially when treatments don't work. High levels of certain inflammatory markers (called cytokines) are linked to poor response to antidepressants, while lower levels are tied to feeling better. Psilocybin may help reduce this inflammation, which could be part of why it helps some people feel better.
Still, we don't fully understand how a person's inflammation levels before treatment, and how those levels change afterward, relate to how well psilocybin works. Figuring this out could help doctors better match patients to psychedelic therapy and discover new ways to treat depression.
In this study, blood samples from a recent study (called the PsiDeR trial) that tested psilocybin in people with treatment-resistant depression will be analyzed. Cytokine levels in these blood samples, as well as levels of another type of molecule linked to inflammation, called mRNA, will be measured.
Detailed description
Chronic and elevated inflammation is associated with depression. Depressed patients tend to have raised inflammatory markers compared to healthy controls, and studies have reported that the greatest elevation is seen in patients with treatment-resistant depression (TRD). Previous studies highlight the bidirectional relationship between inflammation and depression. Elevated pro-inflammatory cytokines are linked to poor antidepressant response, while reductions in these markers are associated with symptom improvement. While neuroinflammation may play a role in the pathophysiology of depression, inflammation is also a causal risk factor for physical illnesses that are often co-morbid with depression, such as cardiovascular disease. As such, targeting inflammation in patients with depression may have significant implications for both their mental and physical health.
Psychedelics are emerging as a potential new class of therapeutic agents for psychiatric illness, including depression. It has been suggested that their therapeutic effect may partly be due to reducing inflammation. Psychedelics have been shown reduce markers of inflammation in models of human inflammatory disease, both in vitro and in vivo. While, as might be expected, psilocybin was not found to reduce markers of inflammation in healthy human volunteers, in a clinical sample of people with treatment-resistant depression, use of ayahuasca (containing the psychedelic N,N DMT) resulted in a significant reduction in CRP levels compared to participants given placebo, with the reduction in CRP levels significantly correlated with a reduction in depressive symptoms. Ayahuasca consists of an admixture of multiple different compounds. As such, the relative contribution of the psychedelic to the anti-inflammatory effect that was observed is unknown.
The effect of isolated psychedelic compounds such as psilocybin on the systemic inflammatory state of patients, specifically patients with depression, therefore, remains to be investigated. Psilocybin's capacity to reduce inflammation, as evidenced in preclinical models, may be a crucial mechanism underlying its therapeutic effects. Moreover, while it is recognised that baseline inflammation levels can influence the effectiveness of conventional antidepressants, it is unclear whether this is also the case for psilocybin.
This study aims to evaluate serum cytokine and inflammatory-related mRNA levels in samples collected from participants with TRD who took part in the (Psi)locybin in (De)pression (R)esistant to Standard Treatments (PsiDeR) Trial, and the relationships between these and psilocybin treatment response. PsiDeR was a randomised, placebo-controlled trial of psilocybin as a treatment for TRD that has now completed.
Study design
- Observational model
- Other
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Psilocybin-treated group blood samples | – | –Blood samples from participants in Psider trial treated with psilocybin 25mg |
| Placebo-treated group blood samples | – | –Blood samples from participants in Psider trial treated with placebo |
Who may qualify
- Ages
- 25 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with treatment-resistant depression, recruited in the UK
Key inclusion criteria (5 listed)
- Fluent in the English language
- Fulfil Diagnostic and Statistical Manual of Mental Disorders (5th Edition) (DSM-5) criteria for current single or recurrent episodes of MDD of at least moderate severity but without psychotic features, as defined on the MINI 7.0.
- 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.
Key exclusion criteria (18 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.
Primary outcome
Linear regression to examine the association between baseline cytokines and depression outcomes at six weeks
Time frame: Six weeks
Linear regression to examine the association between baseline cytokines and depression outcomes at six weeks
1 secondary outcome
Linear regression to examine the association between cytokine level change and depression outcomes at six weeks.
Time frame: Six weeks
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 10 Sep 2025.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Depression - Major Depressive Disorder, 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 5 inclusion and 18 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: under way, not looking for participants, as of the sponsor's last update on 10 Sep 2025. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
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?
Linear regression to examine the association between baseline cytokines and depression outcomes at six weeks (time frame: Six weeks). 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 10 Sep 2025.