P12-13 Safety Assessment and Investigation into the General and Neuro-Toxicologic Potential from Repeated Oral Administration of Cannabinol, TruCBN™

Floraworks TruCBN™ is a proprietary form of cannabinol (CBN), characterized as a high-purity, non-intoxicating, THC-free CBN isolate. CBN is produced from the oxidative decomposition product of cannabidiol (CBD) or tetrahydrocannabinol (THC). Therapeutic properties of CBN include potential efficacy in the treatment of ocular disease, cancer, neurodegeneration, and antimicrobial, anti-inflammatory, immunosuppressive, and soporific effects. TruCBN™ is currently marketed as an alternative to traditional sleep aids such as melatonin. The safety of TruCBN™, at a purity of 99.7%, was examined comprehensively through GLP studies conducted providing a full analytical characterization, method development, and validation of TruCBN™, as well as to analytically support and assess the safety profile, including its genetic, general, and neuro-toxicologic potential. An Ames test was conducted, in which the investigation revealed that there were no concentration or test substance-related increases in the revertant colony numbers in any of the five tester strains (Salmonella typhimurium strains TA98, 100, 1535, 1537, and tester strain Escherichia coli WP2 uvrA). TruCBN™ was determined to be non-mutagenic as it did not induce gene mutation through base pair or frameshift alterations in the genome of the strains. TruCBN™ did not induce structural and/or numerical chromosomal damage in an in vitro micronucleus assay using human peripheral blood lymphocytes with and without S9 metabolic activation. A Maximum Tolerated Dose (MTD) study was utilized to establish tolerable dose levels for repeat-dose studies, in support of reaching a sufficient safety factor for the intended use of 50 mg of TruCBN™ per day in humans. Adjusted dose levels were uitilized in a 14-Day dose-rangefinding study, followed by a 90-Day repeat-dose oral toxicity study, at dose levels of 0 (vehicle control), 100, 200, 400 mg/kg/day in male and female Sprague-Dawley rats, in which there were no adverse effects observed. Specifically, there were no clinical signs, body weight, food consumption, functional observations, or motor activity effects, and no clinical pathology, macroscopic, or microscopic changes attributable to the administration of test substance. Furthermore, results from a Functional Observation Screening Battery (FOB) and Motor Activity (MA) assessment, conducted at the end of the 90-day study demonstrated that there were no findings to suggest TruCNB™ had any effect on behavior or physiological functions in the Test System. There were no microscopic observations in the tissues of the peripheral or central nervous system. The 90-day toxicity study supports a NOAEL for TruCBN™ of 400 mg/kg/day.