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these changes, the scientific literature that should inform public policy regarding harm reduction is inadequate and outdated.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.