Reproductive and developmental toxicity evaluation of cannabidiol

Abstract

An important data gap in determining a safe level of cannabidiol (CBD) intake for consumer use is determination of CBD's potential to cause reproductive or developmental toxicity. We conducted an OECD Test Guideline 421 GLP-compliant study in rats, with extended postnatal dosing and hormone analysis, where hemp-derived CBD isolate (0, 30, 100, or 300 mg/kg-bw/d) was administered orally. Treatment-related mortality, moribundity, and decreased body weight and food consumption were observed in high-dose F₀ adult animals, consistent with severe maternal toxicity. No effects were observed on testosterone concentrations, F₀ reproductive performance, or reproductive organs. Hepatocellular hypertrophy in the 100- and 300 mg/kg-bw/day groups correlated with hypertrophy/hyperplasia in the thyroid gland and changes in mean thyroid hormone concentrations in F₀ animals. Mean gestation length was unaffected; however, total litter loss for two females and dystocia for two additional females in the high-dose group occurred. Other developmental effects were limited to lower mean pup weights in the 300 mg/kg-bw/d group compared to those of concurrent controls. The following NOAELs were identified for CBD isolate based on this study: 100 mg/kg-bw/d for F₀ systemic toxicity and female reproductive toxicity, 300 mg/kg-bw/d for F₀ male reproductive toxicity, and 100 mg/kg-bw/d for F₁ neonatal and F₁ generation toxicity.