Understanding the clinical pharmacology of marijuana-tobacco co-administration

摘要 玛丽琳是一种联邦非法药物，被数百万不同年龄、种族和性别的人使用。 烟草比任何其他可预防的原因都造成更多的疾病和死亡， 人重要的是，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， 大麻和烟草混合使用（也称为共同使用）的健康风险大于 大麻本身的使用。了解导致或导致这两种物质持续共同使用的原因 共同使用的健康后果对维护公共健康很重要。 研究已经描述了摄入β-9-四氢大麻酚（THC），这是一种主要的精神活性化学物质， 大麻，以及各种纯大麻产品的效果，包括烟熏、汽化和口服形式， 但评估大麻和烟草联合作用的研究很少。据我们所 知识，没有研究检查大麻和烟草共同管理的影响，系统地 改变了四氢大麻酚和尼古丁的含量。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。 该项目的主要目的是描述THC-尼古丁的药代动力学和药效学 共同管理。在这项基础研究中，我们将使用活页蒸发器提供剂量的THC和THC 以及大麻和烟草中的尼古丁。我们假设大麻烟草混合物 施用将导致比当物质单独使用时更大的效果，特别是在 低剂量的四氢大麻酚和尼古丁这包括更高的THC和尼古丁摄入量和全身暴露， 超过了心血管反应。我们将检验这些假设，目的如下： (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）描述和比较感官和主观效果，如 高，喜欢，渴望减少，和心理奖励，从管理的各种组合， （3）检查THC和尼古丁的自我管理的差异，从不同的 大麻和烟草的组合在随意访问期间。 这一建议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。 相互作用，第一个操纵THC和尼古丁剂量。它将告诉我们为什么用户 同时使用大麻和烟草以及与同时使用THC和尼古丁有关的潜在健康后果 摄入

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.