Safety Assessment of a Hemp Extract using Genotoxicity and Oral Repeat-Dose Toxicity Studies in Sprague-Dawley Rats

Dziwenka, Margitta; Coppock, Robert; Alexander, McCorkle; Palumbo, Eddie; Ramirez, Carlos; Lermer, Stephen

Humans have been utilizing the Cannabis sativa L. plant for millennia for both medicinal and recreational purposes. The C. sativa L. plant originates from Central Asia and has recently seen an increase in interest likely because of its many applications due to the large phytochemical content as well as being a rich source of both cellulosic and woody fibers [1] . Two preparations of marijuana for recreational use are hashish (resinous) and marijuana (leaves and flowers) [2] . Synthetic cannabinoids are emerging as psychoactive substances and have recreational use [3] . Recreational use of marijuana, hashish synthetic cannabinoids are associated with ischemic and other types of strokes [2] . The cannabinoids, which are oxygen containing aromatic hydrocarbon compounds, are one of the most researched groups of all the phytochemicals in C. sativa L. and include at least 70 compounds, of which delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are some of the most well-known [4] . THC and synthetic cannabinoids have affinity for the cannabinoid receptors. CBD does not have affinity for the cannabinoid 1 receptor (CB1R) and the cannabinoid 2 receptor (CB2R) and there is animal model evidence to show it modulates the adverse effects of ischemic stroke and likely acts on the sigma-1 receptor [5] [6] [7] . Additionally, CBD, in laboratory animal models, has been shown to be a beneficial treatment in substance use disorder including protection of the liver from alcohol damage [8, 9] . The US government recently passed the Agriculture Improvement Act which included changes to the production and marketing of hemp and derivatives of cannabis with extremely low concentrations of delta-9-tetrahydrocannabinol (THC). These changes removed hemp from the Controlled Substances Act, but preserved the US Food and Drug Administrations' (FDA) authority to regulate cannabis and cannabis-derived compounds. This study is investigating the toxicology of a proprietary CBD rich hemp extract.