Impact of Cannabidiol-Rich Hemp Extract Oil on Reconsolidation Disruption of Naturalistic Interoceptive Aversive Memory in Humans
试验速览
- 阶段
- 1 期
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- CO2 Emotional Reactivity
研究概览
简要总结
The purpose of this study is to test whether cannabidiol (CBD) rich hemp extract oil can interfere with the reconsolidation (storage) of pathological fear memory in humans.
详细描述
Preclinical experiments demonstrate that isolated cannabidiol (CBD), the non-psychotomimetic constituent of the Cannabis sativa plant, disrupts reconsolidation of aversive memories conditioned in the laboratory when administered within the memory reconsolidation window (< 6 hrs. post-retrieval) by indirectly activating cannabinoid type-1 (CB1) receptors in the dorsal anterior cingulate cortex (dACC). Furthermore, background material (e.g., terpenoids) naturally present in the cannabis plant may also disrupt aversive memory reconsolidation both alone and in concert with CBD. Based on these preclinical findings, we aim to test whether administration of 300mg CBD-rich hemp extract oil following fear reactivation of an aversive interoceptive threat memory can disrupt reconsolidation of naturalistic aversive memories in humans. More specifically, naturalistic interoceptive aversive memories, a form of transdiagnostic fear memory that contributes to the pathogenesis of fear-related disorders such as panic disorder, posttraumatic stress disorder (PTSD), and illness anxiety disorder.
For this proof-of-concept double-blind trial, volunteers (n=96) reporting elevated fears of somatic sensations will be stratified on biological sex and baseline levels of interoceptive fear and randomized to one of three intervention arms: (a). CBD-rich oil administered within the reconsolidation window, (b). Placebo oil administered within the reconsolidation window, or (c). CBD-rich oil administered outside of the reconsolidation window. Change in emotional reactivity to a 35% CO2 challenge from baseline to two-week follow-up will serve as our primary outcome.
Study findings may contribute towards the development of a novel ultra-brief transdiagnostic intervention guided by reconsolidation theory for individuals prone to fear-related psychiatric disorders.
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)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Fluent in English
- •Willingness to refrain from all non-study cannabis use during the study period.
排除标准
- •Insufficient phobicity (<50 on CO2 challenge);
- •Presence of significant suicidality;
- •History of psychosis;
- •Currently receiving exposure-based treatment;
- •Current substance use disorder;
- •Unstable psychiatric medication for a psychological condition;
- •Medical conditions contraindicating CO2 inhalation (e.g., cardiac arrhythmia, cardiac failure, asthma, lung fibrosis, high blood pressure, epilepsy, or stroke);
- •Any medical problems (e.g., liver or renal abnormalities) or medication use that would preclude ingesting CBD oil, including but not limited to currently taking blood thinners (e.g., Warfarin and some anti-epileptic medications);
- •History of an adverse reaction to CBD oil or other CBD products,
- •Coconut allergy (coconut oil is the carrier oil for CBD-rich extract)
- •(l) Regular cannabis use
研究组 & 干预措施
CBD-WR
- 300 mg CBD-rich hemp extract oil administered within the reconsolidation window.
- The timing of CBD-rich oil administration is based on preclinical studies demonstrating that CBD's disruptive effects on reconsolidation procedurally depend on timing pharmacological administration to be within the memory reconsolidation window (< 6 hrs. post-retrieval).
- Thus, immediately after the 35% CO2 interoceptive memory reactivation procedure and associated measures (see measures), participants will be asked to take a single 300mg CBD-rich oral dose of a hemp-derived oil formulation.
干预措施: Interoceptive Aversive Memory Reactivation (Behavioral)
CBD-WR
- 300 mg CBD-rich hemp extract oil administered within the reconsolidation window.
- The timing of CBD-rich oil administration is based on preclinical studies demonstrating that CBD's disruptive effects on reconsolidation procedurally depend on timing pharmacological administration to be within the memory reconsolidation window (< 6 hrs. post-retrieval).
- Thus, immediately after the 35% CO2 interoceptive memory reactivation procedure and associated measures (see measures), participants will be asked to take a single 300mg CBD-rich oral dose of a hemp-derived oil formulation.
干预措施: Cannabidiol (CBD)-Rich Broad Spectrum Hemp Extract Oil (Dietary Supplement)
PBO-WR
- Placebo administered within the reconsolidation window.
- Immediately after the 35% CO2 interoceptive memory reactivation procedure and associated measures (see measures), participants will be asked to take a single dose of an MCT coconut oil placebo solution.
干预措施: Interoceptive Aversive Memory Reactivation (Behavioral)
PBO-WR
- Placebo administered within the reconsolidation window.
- Immediately after the 35% CO2 interoceptive memory reactivation procedure and associated measures (see measures), participants will be asked to take a single dose of an MCT coconut oil placebo solution.
干预措施: Placebo Oil (Dietary Supplement)
CBD-OR
- CBD-rich hemp extract oil administered outside of the reconsolidation window.
- Participants will be asked to take a single 300mg oral dose of CBD-rich oil approximately 24 hrs after the initial 35% CO2 interoceptive memory reactivation challenge.
- Thus, CBD will be administered well beyond the critical period for memory reconsolidation. The inclusion of this third arm provides a more robust test of the specific reconsolidation theory-based study hypotheses and aids in controlling for any nonspecific possible anxiolytic effects of CBD.
干预措施: Interoceptive Aversive Memory Reactivation (Behavioral)
CBD-OR
- CBD-rich hemp extract oil administered outside of the reconsolidation window.
- Participants will be asked to take a single 300mg oral dose of CBD-rich oil approximately 24 hrs after the initial 35% CO2 interoceptive memory reactivation challenge.
- Thus, CBD will be administered well beyond the critical period for memory reconsolidation. The inclusion of this third arm provides a more robust test of the specific reconsolidation theory-based study hypotheses and aids in controlling for any nonspecific possible anxiolytic effects of CBD.
干预措施: Cannabidiol (CBD)-Rich Broad Spectrum Hemp Extract Oil (Dietary Supplement)
结局指标
主要结局
CO2 Emotional Reactivity
时间窗: Two-week follow-up
Self-reported peak-distress (range: 0-100), defined as the highest level of distress experienced at any point during the 35% CO2 challenge completed at the two-week follow-up assessment, adjusting for baseline rating (immediately after the 35% CO2 challenge, but before receiving either immediate CBD/placebo or delayed CBD).
次要结局
- CO2 Emotional Distress Recovery Trajectory(Two-week follow-up)
- Short Scale Anxiety Sensitivity Index (SASSI)(Two-week)