Understanding the clinical pharmacology of marijuana-tobacco co-administration

了解大麻-烟草联合用药的临床药理学

• 批准号: 10660409
• 负责人: Gideon St.Helen
• 金额: $ 72.66万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10660409
• 关键词: Acute; Affect; Benefits and Risks; Blood flow; Carbon Monoxide; Cardiovascular system; Catecholamines; Cessation of life; Chemicals; Cigarette; Clinical Pharmacology; Data; Disease; Dopamine; Dose; Drug Kinetics; Exposure to; Future; Health; Heart Rate; High Prevalence; Human; Illicit Drugs; Individual; Inhalation; Intake; Joints; Legal; Marijuana; Mission; Modality; National Institute of Drug Abuse; Nicotine; Norepinephrine; Oral; Outcome; Paper; Participant; Pattern; Persons; Pharmaceutical Preparations; Physiological; Pilot Projects; Placebos; Plant Leaves; Plants; Plasma; Platelet aggregation; Public Health; Race; Reaction Time; Recreation; Regulation; Reporting; Research; Rewards; Risk; Self Administration; Sensory; Skin; Smoke; Smoking; Standardization; Study Subject; THC exposure; Testing; Tetrahydrocannabinol; Tobacco; Tobacco Dependence; Tobacco smoke; Tobacco use; Vaporizer; Visit; Weight; age group; aged; cigarette smoking; craving; experience; experimental study; male; marijuana use; marijuana use disorder; marijuana user; motor control; nicotine exposure; pharmacokinetics and pharmacodynamics; pharmacologic; preservation; programs; psychologic; rate of change; response; sex; substance use; tobacco smokers; tobacco user; vaping

ABSTRACT Marijuana, a federal illegal drug, is used by millions of people across all age groups, race, and sex. Tobacco, which causes more disease and death than any other preventable cause, is used by even more people. Importantly, most marijuana users also use tobacco. This is concerning because evidence suggests that the health risk of combined marijuana-tobacco use (also known as co-use) is greater than that caused by use of marijuana by itself. Understanding what leads to or causes sustained co-use of these two substances and the health consequences of co-use is important to preserving public health. Studies have described intake of ∆-9-tetrahydrocannabinol (THC), the primary psychoactive chemical in marijuana, and its effects from various marijuana-only products, including smoked, vaporized, and oral forms, but studies assessing the combined effects of marijuana and tobacco are scarce. To the best of our knowledge, no study has examined effects of marijuana and tobacco co-administration by systematically changing the amount of both THC and nicotine delivered to users. This has been a barrier to understanding the relationship between marijuana-tobacco co-use and health outcomes. The central aim of the project is to describe the pharmacokinetics and pharmacodynamics of THC-nicotine co-administration. In this foundational study, we will use a loose-leaf vaporizer to deliver doses of both THC and nicotine from marijuana and tobacco, respectively. We hypothesize that marijuana-tobacco co- administration will lead to larger effects than when the substances are used by themselves, particularly at lower doses of THC and nicotine. This includes higher THC and nicotine intake and systemic exposure, and more than additive cardiovascular responses. We will test these hypotheses with the following aims: (1) Describe and compare THC and nicotine pharmacokinetics and acute physiologic effects, including, heart rate changes, catecholamine release, skin blood flow, and platelet aggregation from various combinations of marijuana and tobacco; (2) Describe and compare sensory and subjective effects such as high, liking, craving reduction, and psychological reward from administration of various combinations of marijuana and tobacco; (3) Examine differences in self-administration of THC and nicotine from various combinations of marijuana and tobacco during ad libitum access. This proposal will advance the field, providing one of few experimental studies on marijuana-tobacco interaction, the first that manipulates both THC and nicotine dose. It will inform our understanding of why users co-use marijuana and tobacco and of potential health consequences related to simultaneous THC and nicotine intake.

抽象的 大麻是一种联邦非法药物，有数百万不同年龄组、种族和性别的人使用。 烟草比任何其他可预防的原因造成更多的疾病和死亡，使用烟草的人甚至更多 重要的是，大多数大麻使用者也使用烟草，这令人担忧，因为有证据表明。 混合使用大麻和烟草（也称为共同使用）的健康风险大于以下原因造成的健康风险： 单独使用大麻。了解是什么导致或导致这两种物质持续共同使用。 共同使用对健康的影响对于维护公众健康非常重要。 研究描述了摄入 Δ-9-四氢大麻酚 (THC)，这是人体中主要的精神活性化学物质。 大麻，以及各种纯大麻产品的影响，包括熏制、汽化和口服形式， 但就我们所知，评估大麻和烟草的综合影响的研究却很少。 就知识而言，尚无研究系统地检验大麻和烟草共同施用的影响 改变向使用者提供的 THC 和尼古丁的量这一直是理解的障碍。 大麻-烟草共同使用与健康结果之间的关系。 该项目的中心目标是描述 THC-尼古丁的药代动力学和药效学 在这项基础研究中，我们将使用活页蒸发器来输送两种 THC 的剂量。 和尼古丁分别来自大麻和烟草。 服用这些物质会比单独使用这些物质产生更大的影响，特别是在 较低剂量的四氢大麻酚和尼古丁这包括较高的四氢大麻酚和尼古丁摄入量和全身暴露量，以及 我们将通过以下目标来检验这些假设： (1) 描述和比较 THC 和尼古丁的药代动力学和急性生理效应，包括： 心率变化、儿茶酚胺释放、皮肤血流量和血小板聚集 大麻和烟草的组合；（2）描述并比较感官和主观效果，例如 高、喜欢、渴望减少以及通过各种组合的管理获得的心理奖励 大麻和烟草；（3）检查不同来源的 THC 和尼古丁的自我施用差异 随意获取大麻和烟草的组合。 该提案将推动该领域的发展，提供为数不多的大麻烟草实验研究之一 交互，第一个同时控制 THC 和尼古丁剂量的交互，它将帮助我们理解用户的原因。 共同使用大麻和烟草以及与同时使用 THC 和尼古丁相关的潜在健康后果 摄入量。