An Assessment Safety of Acute and Chronic Oral Toxicity studies of High Cannabidiol (CBD) from Female Inflorescence of Cannabis sativa L. (Hemp) Extract in Sprague-Dawley Rats
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Abstract
Cannabis sativa L. contains cannabidiol (CBD), a non-psychoactive cannabinoid with potential therapeutic effects including anxiolytic, hypnotic, and analgesic properties. With increasing global use of CBD-containing products, comprehensive evaluation of their long-term safety is essential. Although pharmacological studies support its benefits, data on the chronic toxicity of high-CBD hemp extracts remain limited. This study aimed to evaluate both the acute and chronic toxicities of high-CBD hemp extract derived from the feminized Candida (CD-1) hemp strain, containing 50.6 + 1.2 % w/w CBD, in accordance OECD guidelines. Acute toxicity was evaluated according to OECD Test Guideline 423 by administering a single dose of 5,000 mg/kg to female rats, which were then observed for 14 days to estimate the LD50. Chronic toxicity was evaluated under OECD Test Guideline 452 in male and female Sprague-Dawley rats administered daily oral doses of 0, 10, 20, and 40 mg/kg b.w./day for 180 days. Hematological, clinical chemistry and urinalysis parameters remained within normal ranges. No mortality or severe toxicological signs were observed during the study period. However, significant reductions in body weight and feed consumption were observed in the medium- and high-dose groups of females as well as the high-dose group of the males, which may be associated with the pharmacological activity of CBD. Centrilobular hepatocyte hypertrophy was observed in both sexes, accompanied by hypertrophy of the pars distalis of the pituitary gland and follicular cell hypertrophy in males. These findings are regarded as adaptive and non‑adverse. Additional minimal to slight changes corresponded to spontaneous background alterations. These findings suggest that the high-CBD hemp extract exhibits low acute toxicity and does not induce significant chronic toxicity at doses up to 40 mg/kg/day in rats.
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