Cannabidiol-Enhanced Cognitive Behavioral Therapy for Generalized Anxiety Disorder
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Change in dorsomedial prefrontal cortex activation when reappraising negative images
研究概览
简要总结
This randomized, double-blind, placebo-controlled clinical trial investigates the use of Food and Drug Administration (FDA)-approved cannabidiol (EPIDIOLEX®) as an adjunct to cognitive behavioral therapy (CBT) in adults with generalized anxiety disorder (GAD). The study aims to evaluate whether cannabidiol-assisted CBT enhances emotion regulation via dorsomedial prefrontal cortex (dmPFC) activation and improves anxiety symptom outcomes compared to CBT with placebo.
详细描述
The study is a randomized, double-blind, placebo-controlled clinical trial evaluating cannabidiol (CBD) as an adjunct to cognitive behavioral therapy (CBT) for treating generalized anxiety disorder (GAD) in adults aged 18-45. Participants will be randomly assigned to one of four arms: (1) Brief CBT with moderate-dose EPIDIOLEX® (10 milligrams(mg)/kilograms(kg)/day), (2) Brief CBT with low-dose EPIDIOLEX® (5 mg/kg/day), (3) Brief CBT with matched placebo with dosing matched to the moderate-dose EPIDIOLEX®, or 4) Brief CBT with matched placebo with dosing matched to the low-dose EPIDIOLEX®. The trial uses a neurobiologically informed experimental medicine approach to evaluate target engagement in the dorsomedial prefrontal cortex (dmPFC) during an emotion regulation functional magnetic resonance imaging (fMRI) task before and after treatment. Primary outcomes include change in dmPFC activation, while secondary outcomes include anxiety symptom severity, treatment tolerability, and plasma concentrations of cannabidiol and related biomarkers.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
All participants, therapists, study staff, and outcomes assessors will be blinded to treatment assignment. Only the principal investigators hold the randomization and blinding key. Placebo is a matched oral solution designed to mimic EPIDIOLEX® in appearance, taste, and smell to maintain effective blinding.
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Right-handed
- •Age 18-45 years at enrollment
- •Able to consent to the study
- •Agree to adhere to lifestyle considerations throughout study duration
- •Generally medically and neurologically healthy, including no evidence of intellectual disability or serious cognitive impairment
- •Have a current generalized anxiety disorder (GAD) diagnosis according to the The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria and/or total scores ≥ 8 on the 7-Item Generalized Anxiety Disorders Scale (GAD-7)
排除标准
- •Clinically significant medical or neurologic condition or neurocognitive dysfunction that would affect function and/or task performance and/or interfere with the study protocol
- •Any current (or within past 2 months) medical condition requiring medication that would interact with cannabidiol or interfere with the study protocol
- •Risk of harm to self or others that requires immediate intervention
- •Presence of contraindications, current or past allergic or adverse reaction, or known sensitivity to cannabinoid-like substances or components of EPIDIOLEX®
- •Positive drug screen or alcohol breathalyzer
- •Unwilling/unable to sign informed consent document
- •Currently pregnant (positive pregnancy test), planning pregnancy, or lactating (women),
- •Under 18 or over 45 years of age
- •Traumatic brain injury, as defined by The American Congress of Rehabilitation as a person who has had a traumatically induced physiological disruption of brain function (i.e., the head being struck, the head striking an object, and/or the brain undergoing an acceleration/deceleration movement [i.e., whiplash] without direct external trauma to the head), as manifested by at least one of the following: any loss of consciousness; any loss of memory for events immediately before or after the injury; any alteration in mental status at the time of the incident; or focal neurological deficits that may or may not be transient)
- •Inability to tolerate small, enclosed spaces without anxiety (e.g. claustrophobia), as determined by self-report and/or a preliminary session in a mock scanner
- •Presence of ferrous-containing metals within the body (e.g., aneurysm clips, shrapnel/retained particles)
- •Receiving concurrent psychotherapy or have received psychotherapy, including for research purposes, within the past year
- •Current moderate or severe alcohol/drug use disorder or in the past 8 weeks
- •Current or past diagnosis of bipolar and other related disorders, schizophrenia spectrum, or other psychotic disorders;
- •GAD-7 score < 8
- •Use of medications known to have severe drug interactions with cannabidiol or that are strong inducers of cytochrome P450 3A4 (CYP3A4) or cytochrome P450 2C19 (CYP2C19)
- •Visual impairment
- •Baseline labs 3 times outside of normal range
- •Use of as needed anti-anxiety medications (e.g., benzodiazepines), unstable dose of other psychoactive drug (i.e., < 4 weeks), or intention to start new treatment during this trial
- •Current or past-month use of cannabis, or a tetrahydrocannabinol (THC) or cannabidiol-containing product (self-report and urine drug screen)
- •Current or past-month coronavirus disease 2019 (COVID-19) diagnosis or febrile illness
- •Treatment with another investigational drug or intervention within the past month
- •Difficulty with or inability to comply with the complete clinical trial.
研究组 & 干预措施
Brief Cognitive Behavioral Therapy + Moderate-Dose Cannabidiol
Participants will receive a 5-week course of brief cognitive behavioral therapy (CBT) combined with oral cannabidiol (EPIDIOLEX®) at a moderate dose. Dosing starts at 5 milligram/kilogram/day and titrates to 10 milligram/kilogram/day (divided twice a day) after 6 days. Cannabidiol is administered chronically throughout CBT to examine target engagement and symptom outcomes.
干预措施: Moderate-Dose Cannabidiol (Drug)
Brief Cognitive Behavioral Therapy + Low-Dose Cannabidiol
Participants will receive a 5-week course of brief cognitive behavioral therapy (CBT) combined with a lower dose of oral cannabidiol (EPIDIOLEX®), maintained at 5 milligram/kilogram/day (divided twice a day) throughout the treatment period. No titration is required.
干预措施: Low-Dose Cannabidiol (Drug)
Brief Cognitive Behavioral Therapy + Placebo Titrated to Match Moderate-Dose Cannabidiol
Participants will receive a 5-week course of brief cognitive behavioral therapy (CBT) combined with a matched placebo oral solution. The placebo mimics the appearance, smell, and taste of EPIDIOLEX®. For blinding the moderate dose cannabidiol arm, dosing starts at 5 milligram/kilogram/day and titrates to 10 milligram/kilogram/day (divided twice a day) after 6 days.
干预措施: Placebo Matched to Moderate-Dose Cannabidiol (Drug)
Brief Cognitive Behavioral Therapy + Placebo Titrated to Match Low-Dose Cannabidiol
Participants will receive a 5-week course of brief cognitive behavioral therapy (CBT) combined with a matched placebo oral solution. The placebo mimics the appearance, smell, and taste of EPIDIOLEX®. For blinding the low-dose cannabidiol arm, dosing is maintained at 5 milligram/kilogram/day (divided twice a day) throughout the treatment period. No titration is required.
干预措施: Placebo Matched to Low-Dose Cannabidiol (Drug)
结局指标
主要结局
Change in dorsomedial prefrontal cortex activation when reappraising negative images
时间窗: Baseline to post-treatment (~Week 5)
Within-participant change in dorsomedial prefrontal cortex (dmPFC) activation will be calculated as post-treatment minus baseline values during an explicit emotion regulation task (Reappraise \> Maintain contrast). Measured using blood-oxygen-level-dependent (BOLD) signal from multi-echo functional magnetic resonance imaging (fMRI).
次要结局
- Post-treatment dorsomedial prefrontal cortex activation when reappraising negative images(Post-treatment (~Week 5))
- Post-treatment amygdala activation when reappraising negative images(Post-treatment (~Week 5))
- Change in amygdala activation when reappraising negative images(Baseline to post-treatment (~Week 5))
- Post-treatment hippocampal activation when reappraising negative images(Post-treatment (~Week 5))
- Change in hippocampal activation when reappraising negative images(Baseline to post-treatment (~Week 5))
- Post-treatment inferior frontal gyrus activation when reappraising negative stimuli(Post-treatment (~Week 5))
- Change in inferior frontal gyrus activation when reappraising negative images(Baseline to post-treatment (~Week 5))
- Post-treatment anterior insula activation when reappraising negatives images(Post-treatment (~Week 5))
- Change in anterior insula activation when reappraising negative images(Baseline to post-treatment (~Week 5))
- Change in plasma concentration of anandamide from baseline to post-treatment(Baseline and post-treatment (~Week 5))
- Change in plasma concentration of 2-arachidonoylglycerol (2-AG) from baseline to post-treatment(Baseline and post-treatment (~Week 5))
- Change in plasma concentration of cannabidiol from baseline to post-treatment(Baseline and post-treatment (~Week 5))
- Change in plasma concentration of 7-hydroxy-cannabidiol (7-OH-CBD) from baseline to post-treatment(Baseline and post-treatment (~Week 5))
- Post-treatment dorsomedial prefrontal cortex activation during implicit emotion regulation(Post-treatment (~Week 5))
- Change in dorsomedial prefrontal cortex activation during implicit emotion regulation(Baseline to post-treatment (~Week 5))
- Post-treatment ventromedial prefrontal cortex activation during implicit emotion regulation(Post-treatment (~Week 5))
- Change in ventromedial prefrontal cortex activation during implicit emotion regulation(Baseline to post-treatment (~Week 5))
- Change in depressive symptom severity(Baseline and post-treatment (~Week 5))
研究者
Hilary Marusak
Associate Professor, Department of Psychiatry and Behavioral Neuroscience
Wayne State University