Subchronic oral toxicity assessment of a cannabis extract

Cannabidiol (CBD) is present in Cannabis Sativa L. and has been used in medicines and foods to deliver beneficial health effects. Despite this, research on CBD safety utilising modern testing methods is lacking. Therefore three separate safety experiments were performed on a CBD isolate. Sprague-Dawley rats were used to investigate prenatal development, a 14-day toxicity sighting study, and an OECD compliant 90-day subchronic oral toxicity trial, with 35-day off-dose recovery. The prenatal screening study demonstrated reduced body weights and food consumption in the highest dose group, but no substance-related changes in pregnancy rate, maternal or placental gross abnormalities, or premature deliveries. The 14-day study indicated tolerance up to 460 mg/kg bw/d of CBD isolate. Based on these findings, a 90-day repeated dose oral toxicity study was performed at doses of 0, 30, 115, 230, and 460 mg/kg bw/d of CBD, followed by a 35-day off-dose recovery period. In the 90-day study, some non-adverse organ and tissue changes were observed. With the exception of the high dose group, these fully reversed during the recovery period. Based on these findings, sub-chronic consumption of highly purified isolate results in a CBD NOAEL of 460 mg/kg bw/d for males and 230 mg/kg bw/d for females.