Clinical trial 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Major Depressive Disorder
Keywords: Psilocybin
Cognitive Behavioral Therapy (CBT)
Randomized Controlled Trial
Psychedelic Therapy
Inflammatory Markers
Lead sponsor: Khyber Medical University Peshawar
Sponsor class: OTHER
First posted: 2024-12-24
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment (The study has four distinct intervention groups: Control, Psilocybin Therapy, CBT, and Psilocybin-assisted CBT.)
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Change in Depression Scores (Hamilton Depression Rating)
timeFrame: Baseline, Week 6 (end of the first psilocybin session), and Week 10 (end of intervention).
measure: Change in Depression Scores (Montgomery-Åsberg Depression Rating Scale)
timeFrame: Baseline, Week 6 (end of the first psilocybin session), and Week 10 (end of intervention).
measure: Change in Depression Scores (Beck Depression Inventory)
timeFrame: Baseline, Week 6 (end of the first psilocybin session), and Week 10 (end of intervention).
measure: Change in Anxiety Scores (Beck Anxiety Inventory)
timeFrame: Baseline, Week 6 (end of the first psilocybin session), and Week 10 (end of intervention).
Secondary outcomes:
measure: Change in Brain-Derived Neurotrophic Factor (BDNF) Levels
timeFrame: Baseline, Week 6, and Week 10
measure: Change in Oxytocin Levels
timeFrame: Baseline, Week 6, and Week 10
measure: Change in Inflammatory Markers
timeFrame: Baseline, Week 6, and Week 10.
measure: Deviation from Balanced Time Perspective (DBTP)
timeFrame: Baseline, Week 6, and Week 10.
measure: EEG Pattern Changes
timeFrame: Baseline, Week 6, and Week 10.
Other outcomes:
Locations:
city: Peshawar
country: Pakistan
facility: Lady Reading Hospital, Pakistan
state: Khyber Pakhtunkhwa
Study officials:
affiliation: Hayat Abad Medical Complex, Peshawar.
name: Dr Mahvash Khan
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lee YJ, Lee GW, Seo WS, Koo BH, Kim HG, Cheon EJ. Neurofeedback Treatment on Depressive Symptoms and Functional Recovery in Treatment-Resistant Patients with Major Depressive Disorder: an Open-Label Pilot Study. J Korean Med Sci. 2019 Nov 4;34(42):e287. doi: 10.3346/jkms.2019.34.e287.
citation: MacCallum CA, Lo LA, Pistawka CA, Deol JK. Therapeutic use of psilocybin: Practical considerations for dosing and administration. Front Psychiatry. 2022 Dec 1;13:1040217. doi: 10.3389/fpsyt.2022.1040217. eCollection 2022.
citation: Dodd S, Norman TR, Eyre HA, Stahl SM, Phillips A, Carvalho AF, Berk M. Psilocybin in neuropsychiatry: a review of its pharmacology, safety, and efficacy. CNS Spectr. 2023 Aug;28(4):416-426. doi: 10.1017/S1092852922000888. Epub 2022 Jul 11.
citation: Mertens LJ, Wall MB, Roseman L, Demetriou L, Nutt DJ, Carhart-Harris RL. Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression. J Psychopharmacol. 2020 Feb;34(2):167-180. doi: 10.1177/0269881119895520. Epub 2020 Jan 16.
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