Understanding the clinical pharmacology of marijuana-tobacco co-administration

摘要 大麻是一种联邦非法药物，各年龄段、种族和性别的数百万人都在使用。 烟草比其他任何可预防的原因导致更多的疾病和死亡，更多的人使用烟草。 人民。重要的是，大多数吸食大麻的人也使用烟草。这令人担忧，因为有证据表明 大麻和烟草联合使用(也称为联合使用)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保护公众健康很重要。 研究已经描述了∆-9-四氢大麻酚(THC)的摄入量，THC是人体内主要的精神活性化学物质 大麻及其各种纯大麻产品的影响，包括烟熏、蒸发和口服形式， 但评估大麻和烟草的综合影响的研究很少。尽我们最大努力 知识，还没有研究通过系统地检查大麻和烟草联合给药的影响 改变传递给使用者的THC和尼古丁的量。这一直是理解 大麻-烟草联合使用与健康结局的关系。 该项目的中心目标是描述尼古丁的药代动力学和药效学。 共同管理。在这项基础性研究中，我们将使用活页雾化器来传递两种剂量的THC 以及分别来自大麻和烟草的尼古丁。我们假设大麻-烟草联合- 与单独使用这些物质相比，给药会产生更大的影响，特别是在 较低剂量的THC和尼古丁。这包括更高的THC和尼古丁摄入量以及全身暴露，以及 不仅仅是附加的心血管反应。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)描述和比较感官和主观效果，如 高，喜欢，渴望减少，从管理的各种组合的心理奖励 大麻和烟草；(3)检查不同来源的THC和尼古丁自我给药的差异 在自由出入期间，大麻和烟草的组合。 这项提议将推进这一领域，提供为数不多的关于大麻-烟草的实验研究之一 相互作用，第一个同时控制THC和尼古丁剂量的药物。它将让我们了解为什么用户 共同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 入口处。

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.