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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change in Depression Scores (Hamilton Depression Rating)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
Randomized (Random allocation will be performed using a simple lottery method.)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
研究组 & 干预措施
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.
干预措施: Psilocybin (Drug)
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.
干预措施: Cognitive Behavioral Therapy (CBT) (Behavioral)
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.
干预措施: Psilocybin (Drug)
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.
干预措施: Cognitive Behavioral Therapy (CBT) (Behavioral)
结局指标
主要结局
Change in Depression Scores (Hamilton Depression Rating)
时间窗: Baseline, Week 6 (end of the first psilocybin session), and Week 10 (end of intervention).
Assessment of changes in depression scores using the Hamilton Depression Rating Scale (HAM-D), a clinician-administered tool for evaluating the severity of depression. Unit of Measure: Points on the HAM-D scale. The HAM-D consists of 17 items, each assessing a specific depressive symptom. Each item is rated on a 0-4 or 0-2 scale, depending on the item. The total score ranges from 0 to 52. Higher scores indicate greater severity of depressive symptoms. 0-7: Normal 8-13: Mild depression 14-18: Moderate depression 19-22: Severe depression * 23: Very severe depression
Change in Depression Scores (Montgomery-Åsberg Depression Rating Scale)
时间窗: Baseline, Week 6 (end of the first psilocybin session), and Week 10 (end of intervention).
Assessment of changes in depression scores using the Montgomery-Åsberg Depression Rating Scale (MADRS), a clinician-administered scale for evaluating depressive symptom severity. Unit of Measure: Points on the MADRS scale. The MADRS consists of 10 items, each assessing a specific depressive symptom. Each item is rated on a 0-6 scale. The total score ranges from 0 to 60. Higher scores indicate greater severity of depressive symptoms. 0-12: Normal 13-19: Mild depression 20-34: Moderate depression * 35: Severe depression
Change in Depression Scores (Beck Depression Inventory)
时间窗: Baseline, Week 6 (end of the first psilocybin session), and Week 10 (end of intervention).
Assessment of changes in depression scores using the Beck Depression Inventory (BDI), a self-reported measure designed to evaluate the severity of depression symptoms. Unit of Measure: Points on the BDI scale. The BDI consists of 21 items, each assessing a specific depressive symptom. Each item is rated on a 4-point scale. The total score ranges from 0 to 63. Higher scores indicate greater severity of depressive symptoms. 0-13: Normal 14-19: Mild depression 20-28: Moderate depression 29-63: Severe depression
Change in Anxiety Scores (Beck Anxiety Inventory)
时间窗: Baseline, Week 6 (end of the first psilocybin session), and Week 10 (end of intervention).
Assessment of changes in anxiety scores using the Beck Anxiety Inventory (BAI), a self-reported questionnaire for evaluating the severity of anxiety symptoms. Unit of Measure: Points on the BAI scale. The BAI consists of 21 items, each assessing a specific anxiety symptom. Each item is rated on a 0-3 scale. The total score ranges from 0 to 63. Higher scores indicate greater severity of anxiety symptoms. 0-7: Normal 8-15: Mild anxiety 16-25: Moderate anxiety 26-63: Severe anxiety
次要结局
- Change in Brain-Derived Neurotrophic Factor (BDNF) Levels(Baseline, Week 6, and Week 10)
- Change in Oxytocin Levels(Baseline, Week 6, and Week 10)
- Change in Inflammatory Markers(Baseline, Week 6, and Week 10.)
- Deviation from Balanced Time Perspective (DBTP)(Baseline, Week 6, and Week 10.)
- EEG Pattern Changes(Baseline, Week 6, and Week 10.)