Unlike pharmaceutical medications, marijuana is not a single-agent compound but a complex combination of more than 100 different chemicals, which include cannabinoids, flavonoids, and terpinoids. The primary psychoactive component of marijuana is delta-9-tetrahydrocannabinol (THC). However, other cannabinoid compounds—including cannabidiol (CBD), cannabinol, cannabichromene, cannabidivarin, cannabigerol, and tetrahydrocannabivarin—have their own actions on the central nervous system and may modify the effects of THC (“entourage effects”). The concentration of these compounds can vary substantially (4), making it difficult to characterize the specific positive or negative health effects of marijuana, especially in uncontrolled and epidemiological studies. In addition, the average content of THC in marijuana (as measured in confiscated marijuana samples in the United States) has increased substantially from ∼1% in the 1980s to ∼9% in 2008 (5, 6). As THC is thought to be related to many of marijuana's adverse effects, this increase in potency means that relying on older studies for data about marijuana's safety profile may be problematic. Furthermore, given that individual cannabinoids present in whole-plant marijuana have different pharmacological effects, data on individual cannabinoids cannot necessarily be extrapolated to whole-plant
