Marijuana Harm Reduction: Innovative Strategies for Developing New Knowledge

描述（由申请人提供）：在过去的两年中，美国在接受大麻方面发生了巨大的变化。2015年，科罗拉多州官员预计合法市场的需求将超过130吨。鉴于这些变化，应该为减少危害的公共政策提供信息的科学文献是不充分和过时的。如果科学家要对大麻的监管产生影响，现有文献中有许多关键的限制需要解决。科学家需要了解常用大麻品种的影响，因为它们在日常生活中被使用，而不是仅仅依靠在受控的实验室实验中测试政府种植的大麻的影响。此外，科学家需要将大麻的作用概念化为不同大麻素的复合作用，特别是四氢大麻酚（THC）和大麻二酚（CBD）。CBD与四氢大麻酚的比例可能对大麻的效果有重要影响，这反过来可能对减少危害有重要影响。这项研究的总体目标是利用高外部效度的观察设计，对不同种类大麻的潜在危害有更细致的了解，从而避免了以往研究的许多局限性。第一个具体目标将检查三种在四氢大麻酚效力（6%,12%,18%）上显着不同但在其他主要大麻素效力（< 0.5%）上没有差异的菌株，以确定四氢大麻酚水平是否与增加的中毒和更大的有害影响有关。据推测，大麻的效力越强，血液中四氢大麻酚的含量就越高，工作记忆就越差，对毒品的回报也越高。第二个具体目标将检查CBD是否能缓和四氢大麻酚的有害影响，并确定CBD与四氢大麻酚的比例，有害影响最低。为此，180名常客将被分配到五种大麻中的一种，这些大麻的CBD和THC的比例不同，大约在1:20到20:1之间。据推测，具有高CBD与四氢大麻酚比例的菌株在记忆和药物奖励方面的危害最小。从这项研究中获得的信息将告知公众不同大麻素和菌株的潜在危害。它

DESCRIPTION (provided by applicant): Over the last two years, the United States has witnessed enormous changes concerning the acceptance of marijuana. In 2015, Colorado state officials expect demand in the legal market to exceed 130 metric tons. Given these changes, the scientific literature that should inform public policy regarding harm reduction is inadequate and outdated. There are a number of critical limitations in the extant literature that need to be addressed if scientists are to have an influence on the regulation of marijuana. Scientists need to understand the effects of commonly used marijuana strains, as they are used in everyday life, as opposed to relying solely on testing the effects of government grown marijuana in controlled laboratory experiments. In addition, scientists need to conceptualize the effects of marijuana as the compound action of different cannabinoids, specifically tetrahydrocannabinol (THC) and cannabidiol (CBD). The ratio of CBD to THC may have an important impact on the effects of the marijuana, which in turn may have important implications for harm reduction. The overarching objective of the proposed research is to advance a more nuanced understanding of the potential harm associated with different strains of marijuana, using an observational design with high external validity, thereby avoiding many of the limitations of previous research. The first specifi aim will examine three strains that differ markedly on THC potency (6%, 12%, 18%) but do not differ on the potency of other major cannabinoids (< .5%) to determine whether the level of THC is associated with increased intoxication and greater harmful effects. It is hypothesized that the higher potency marijuana will be associated with greater blood levels of THC and diminished working memory and increased ratings of drug reward. The second specific aim will examine whether CBD moderates the harmful effects of THC and will identify the ratio of CBD to THC with the lowest harmful effects. To this end, 180 regular users will be assigned to one of five strains of marijuana with different ratios of CBD to THC, ranging approximately from 1:20 to 20:1. It is hypothesized that the strains with a high CBD to THC ratio will demonstrate the least amount of harm on measures of memory and drug reward. The information gained from this research will inform the public about the potential harms of different cannabinoids and strains. It may also have a translational application with respect to identifying THC levels or CBD to THC ratios that could be the focus of future regulatory actions.