The Impact of Product Formulation on the Pharmacokinetics and Pharmacodynamics of Delta-9THC-Infused Cannabis Edibles

产品配方对 Delta-9THC 注入大麻食品的药代动力学和药效学的影响

• 批准号: 10706572
• 负责人: Tory Richard Spindle
• 金额: $ 64.66万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10706572
• 关键词: Acute; Adult; Adverse effects; Adverse event; Area Under Curve; Biological Availability; Blood specimen; Candy; Cannabinoids; Cannabis; Cannabis retail; Categories; Characteristics; Chemicals; Chocolate; Clinical; Clinical Research; Cognitive; Collaborations; Consumption; Controlled Study; Data; Dependence; Dietary Fats; Dose; Double-Blind Method; Drug Kinetics; Education; Emergency department visit; Epidemiology; Exposure to; Fasting; Fatty acid glycerol esters; Female; Food; Formulation; Fostering; Future; Human; Incidence; Ingestion; Intoxication; Knowledge; Laboratories; Laboratory Study; Lipids; Liquid substance; Marketing; Measures; Monitor; Oral; Outcome; Outpatients; Participant; Pharmaceutical Preparations; Pharmacodynamics; Physiological; Placebo Control; Placebos; Plasma; Policies; Process; Psychomotor Impairments; Psychomotor Performance; Questionnaires; Randomized; Reaction; Reporting; Research; Route; Sex Differences; Task Performances; Technology; Time; Woman; Work; absorption; abuse liability; adverse event risk; clinical decision-making; decision research; design; hydrophilicity; insight; male; marijuana legalization; marijuana user; men; nano; nanoemulsion; novel; pharmacokinetics and pharmacodynamics; pre-clinical research; preclinical study; stem

PROJECT SUMMARY/ABSTRACT As cannabis legalization has expanded, many novel products have emerged. Oral cannabis products (or “edibles”) are among the most popular. Similar to traditional forms of cannabis, edibles that contain delta-9- tentrahydrocannabinol (THC) as the primary constituent have abuse liability and can produce unwanted negative effects (e.g., cognitive/psychomotor impairment, panicked reactions). Cannabis users often report that edibles produce highly unpredictable effects, making these products prone to eliciting adverse events. Edibles are responsible for most emergency room visits related to cannabis over-intoxication. Inconsistency in cannabis edible effects likely stems, in part, from the large variety of formulations within this diverse product category. Preclinical research has shown that THC absorption is markedly increased when ingested in lipid or “nanoemulsion” formulations relative to non-lipid or non-nanoemulsion formulations; nanoemulsion is a process used to make cannabinoids more hydrophilic and purportedly, more bioavailable. Thus, these formulation characteristics may directly impact the magnitude of THC absorption and THC-related acute effects in humans. However, controlled clinical research on cannabis edibles is limited and few studies have evaluated if the formulation of these products influences pharmacokinetic (PK) or pharmacodynamic (PD) outcomes. The proposed, double-blind, placebo-controlled human laboratory study will compare the PK and PD effects of 3 popular types of cannabis edibles: THC-infused chocolates, gummies, and drinks. We hypothesize that THC absorption and resultant PD effects will be significantly greater for the chocolate (high lipid concentration) and drink (nanoemulsion formulation) relative to the gummy (low lipid concentration and no nanoemulsion). Healthy adults will attend 9 outpatient laboratory sessions. For each session, they will consume 1 of 3 cannabis edible formulations (chocolate, gummy, or nanoemulsion drink) at either 0mg THC (placebo), 10mg THC, or 25mg THC (i.e., 2 and 5 Standard THC Units, STUs); sessions will be preceded by 8 hrs of monitored overnight fasting. Sessions will be completed in a randomized order and separated by at least 1 week. PD assessments will include a battery of cognitive/psychomotor performance tasks and a subjective drug effect questionnaire, all shown to be sensitive to cannabis at the proposed STUs. Blood plasma will be collected to quantify concentrations of THC and its primary metabolites (11-OH-THC, THCCOOH). This project will determine whether the formulation of cannabis edibles influences PK/PD effects when THC doses are held constant, which is of growing importance given initiatives to utilize STUs for research and regulatory purposes. Data generated from this project can potentially inform educational efforts to reduce the incidence of adverse events caused by cannabis edibles and provide insight into whether cannabis edible formulation should be a consideration, in conjunction with STUs, for research, regulatory, and clinical decisions.

项目概要/摘要 随着大麻合法化的扩大，出现了许多新型产品口服大麻产品（或。 与传统形式的大麻类似，含有 delta-9- 的食品是最受欢迎的。 四氢大麻酚 (THC) 作为主要成分，具有滥用倾向，可能会产生不必要的负面影响 大麻使用者经常报告食用大麻的影响（例如认知/精神运动障碍、恐慌反应）。 产生高度不可预测的影响，使这些产品容易引发不良事件。 负责大多数与大麻过度中毒相关的急诊室就诊。 可食用效果可能部分源于这一多样化产品类别中的多种配方。 临床前研究表明，以脂质或脂质形式摄入时，THC 吸收显着增加。 “纳米乳液”制剂相对于非脂质或非纳米乳液制剂是一个过程； 用于使大麻素更具亲水性，并且据称具有更高的生物利用度。 特性可能直接影响人类 THC 吸收的程度和 THC 相关的急性影响。 然而，有关大麻食品的对照临床研究有限，很少有研究评估大麻是否可以 这些产品的配方会影响药代动力学 (PK) 或药效学 (PD) 结果。 拟议的双盲、安慰剂对照人体实验室研究将比较 PK 和 PD 效应 3 种流行的大麻食品：添加 THC 的巧克力、软糖和饮料。 巧克力（高脂质浓度）和 饮料（纳米乳液配方）相对于软糖（低脂质浓度且无纳米乳液）。 成人将参加 9 次门诊实验室会议，每次会议他们将消耗 3 份大麻食用品中的 1 份。 0mg THC（安慰剂）、10mg THC 或 25mg THC 的配方（巧克力、软糖或纳米乳液饮料） （即 2 和 5 个标准 THC 单位，STU）；训练前将进行 8 小时的夜间禁食监测。 会议将按随机顺序完成，并至少间隔 1 周进行 PD 评估。 一系列认知/精神运动表现任务和主观药物效应问卷，所有这些都表明 在拟议的 STU 中对大麻敏感 将收集血浆以量化 THC 浓度。 及其主要代谢物（11-OH-THC、THCCOOH） 本项目将确定是否配制。 当 THC 剂量保持不变时，大麻食品会影响 PK/PD 效应，这一点越来越重要 鉴于利用 STU 进行研究和监管目的的举措，该项目生成的数据可以。 可能为减少大麻食品引起的不良事件发生率的教育工作提供信息， 深入了解大麻食用配方是否应与 STU 一起考虑 研究、监管和临床决策。