NCT06746441

Effect of Psilocybin Only and Psilocybin Assisted Cognitive Behavioral Therapy in the Management of Major Depressive Disorder and Associated Metabolic, Immune, Inflammatory, Neuroplasticity and Electrical Activity Markers

Effect of Psilocybin Only and Psilocybin Assisted Cognitive Behavioral Therapy in the Management of Major Depressive Disorder and Associated Metabolic, Immune, Inflammatory, Neuroplasticity and Electrical Activity Markers: a Randomized Controlled Trial

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (actual)
• Sponsor: Khyber Medical University Peshawar · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This randomized controlled clinical trial evaluates the effectiveness of psilocybin and psilocybin-assisted cognitive behavioral therapy (CBT) in the management of Major Depressive Disorder (MDD). The study aims to compare the effects of psilocybin-only therapy, CBT, and psilocybin-assisted CBT on depression symptoms, neurochemical markers, inflammatory markers, and neuroplasticity in individuals with MDD. Participants will continue their routine depression medications and will be assessed for changes in depression scores, biochemical markers, and brain activity patterns using validated tools and tests.

Detailed description

This single-masked randomized controlled trial investigates novel therapeutic interventions for Major Depressive Disorder (MDD). MDD is a leading cause of disability worldwide, with a significant proportion of patients being treatment-resistant or showing only partial response to conventional antidepressants. Emerging evidence suggests that psilocybin, a serotonergic psychedelic, has potential as a rapid-acting antidepressant. The study will recruit 60 participants meeting DSM-V criteria for MDD, randomized into four groups: Control group (Conventional therapy only), Psilocybin therapy group, Cognitive Behavioral Therapy (CBT) group, and Psilocybin-assisted CBT group. Participants will receive interventions over 10 weeks, with psilocybin administered in two heroic doses six weeks apart, and CBT delivered in 8-10 structured sessions. Biochemical and neurochemical markers such as CD4/CD8 ratio, TNF-α, IL-6, BDNF, and oxytocin will be measured, along with inflammatory markers (resistin and visfatin). Depression scores will be assessed using scales like HAM-D, MADRS, and BDI. EEG recordings will evaluate changes in brain activity pre- and post-intervention. The primary objective is to assess improvements in depression symptoms, while secondary objectives include evaluating changes in immune, inflammatory, and neurochemical markers and EEG activity. Data will be analyzed using ANOVA with Tukey's post-hoc tests to determine statistical significance.

Conditions

• Major Depressive Disorder

Interventions

Type	Name	Description
DRUG	Psilocybin	Psilocybin is a naturally occurring serotonergic psychedelic compound found in Psilocybe mushrooms. It is metabolized in the body into its active form, psilocin, which has a high affinity for serotonin 5-HT2A receptors. This enables psilocin to bypass the default serotonin pathway, producing antidepressant effects. For this study: Psilocybin will be administered orally in a dose of 5-6 grams per session. Each participant in the Psilocybin and Psilocybin-assisted CBT arms will receive two sessions spaced six weeks apart. The therapy will be conducted in a controlled hospital setting with medical monitoring during the session to ensure safety until the hallucination phase subsides. Psilocybin will be added to routine antidepressant medication.
BEHAVIORAL	Cognitive Behavioral Therapy (CBT)	Cognitive Behavioral Therapy (CBT) is a structured, time-limited psychotherapy aimed at alleviating symptoms of depression. It involves addressing negative thoughts and behavioral patterns through the following steps: Identifying troubling life situations. Recognizing thoughts, emotions, and beliefs about those situations. Identifying negative or inaccurate thinking patterns. Restructuring those thoughts into positive and realistic perspectives. In this study: CBT will consist of 8-10 structured sessions, each lasting approximately 90 minutes. Participants will attend therapy sessions twice weekly over a six-week period. The intervention will be delivered by trained psychotherapists in a controlled hospital setting. Routine antidepressant medications will be continued alongside CBT.

Timeline

• Start date: 2024-12-01
• Primary completion: 2025-06-01
• Completion: 2025-07-30
• First posted: 2024-12-24
• Last updated: 2025-09-02

Locations

1 site across 1 country: Pakistan