Measurement of Serum Inflammatory Markers in Patients Treatment-resistant Depression Given Psilocybin

NCT07164755 | Active Not Recruiting

• 1 other identifier: 357453
• Study Type: observational
• Target: 46
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Depression - Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• 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

  Six weeks

Secondary Outcomes (1)

• Linear regression to examine the association between cytokine level change and depression outcomes at six weeks.

  Six weeks

Study Arms (2)

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

Eligibility Criteria

• Age: 25 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with treatment-resistant depression, recruited in the UK

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• King's College London: lead

Study Sites (1)

King's College London Institute of Psychiatry, Psychology and Neuroscience

London, SE5 8AF, United Kingdom

Location

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2025
• First Posted: September 10, 2025
• Study Start: June 21, 2021
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: September 10, 2025

Record last verified: 2025-09

Locations

GB (1)