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

Khyber Medical University Peshawar

Status and phase: Completed; Phase 2

Conditions: Major Depressive Disorder

Treatments: Behavioral: Cognitive Behavioral Therapy (CBT); Drug: Psilocybin

Study type: Interventional

Funder types: Other

Identifiers

NCT06746441

KMU/DIR/CTU/2024/011

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Individuals aged 18-70 years.
• Diagnosed with Major Depressive Disorder (MDD) according to DSM-V criteria.
• Active depressive symptoms as indicated by a score > 16 on the Hamilton Depression
• Rating Scale (HAM-D) over the preceding two weeks.
• Female participants of childbearing potential must be using a highly effective form of contraception and willing to maintain contraceptive use throughout the study period.
• Participants must have been taking one SSRI antidepressant (e.g., citalopram, escitalopram, fluoxetine) for at least 6 weeks with at least 75% adherence.

Exclusion criteria

• Resting blood pressure >140/90 (average of four separate measurements).
• Risk of suicidal tendencies as indicated by a score of 3 or higher on item 3 of the HAM-D scale.
• Use of multiple SSRIs or any antidepressant not specified in the inclusion criteria.
• Presence of concurrent psychiatric disorders (e.g., bipolar disorder, schizophrenia).
• Use of psychedelics or ketamine within the last 12 months.
• Pregnancy, breastfeeding, or attempting to conceive.
• History of substance abuse or alcohol use in the last 6 months.
• Cardiovascular conditions (e.g., hypertension, stroke history).
• History of seizures or epilepsy.
• Diabetes (especially insulin-dependent).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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60 participants in 4 patient groups

Psilocybin Therapy Group

Experimental group

Description:

Participants will receive two oral doses of psilocybin (5-6 grams per dose), administered six weeks apart. Each session will occur in a controlled environment with medical monitoring until the hallucination phase subsides. Participants will continue their routine antidepressant medications during the study.

Treatment:

Drug: Psilocybin

Control Group

No Intervention group

Description:

Participants will continue their routine antidepressant medications (e.g., SSRIs such as citalopram, escitalopram, or sertraline) without any additional intervention.

Cognitive Behavioral Therapy (CBT) Group

Active Comparator group

Description:

Participants will undergo 8-10 structured sessions of Cognitive Behavioral Therapy over six weeks. Each session will last approximately 90 minutes, focusing on restructuring negative thought patterns and addressing depression symptoms. Participants will continue their routine antidepressant medications during the study.

Treatment:

Behavioral: Cognitive Behavioral Therapy (CBT)

Psilocybin-Assisted CBT Group

Active Comparator group

Description:

Participants will receive both psilocybin therapy and Cognitive Behavioral Therapy. Psilocybin will be administered in two oral doses (5-6 grams per dose), six weeks apart, with medical monitoring during sessions. In addition, participants will undergo 8-10 CBT sessions over six weeks. Routine antidepressant medications will be continued.

Treatment:

Drug: Psilocybin

Behavioral: Cognitive Behavioral Therapy (CBT)