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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-01

Study Completion Date

2025-07-30

Brief Summary

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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.

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Detailed Description

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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

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Major Depressive Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Parallel Assignment (The study has four distinct intervention groups: Control, Psilocybin Therapy, CBT, and Psilocybin-assisted CBT.)

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Randomized (Random allocation will be performed using a simple lottery method.)

Study Groups

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Psilocybin Therapy Group

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.

Group Type EXPERIMENTAL

Psilocybin

Intervention Type DRUG

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.

Control Group

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Cognitive Behavioral Therapy (CBT) Group

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.

Group Type ACTIVE_COMPARATOR

Cognitive Behavioral Therapy (CBT)

Intervention Type BEHAVIORAL

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.

Psilocybin-Assisted CBT Group

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.

Group Type ACTIVE_COMPARATOR

Psilocybin

Intervention Type DRUG

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.

Cognitive Behavioral Therapy (CBT)

Intervention Type BEHAVIORAL

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type BEHAVIORAL

Other Intervention Names

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Psilocin (the active form of psilocybin metabolized in the body)

Eligibility Criteria

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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.

* 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).

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.

Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No