Reproductive and developmental toxicity evaluation of cannabidiol

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 ani-mals. 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 gen-eration toxicity.

Automated summary

A study was conducted on rats to determine the potential reproductive or developmental toxicity of cannabidiol (CBD). High doses of CBD caused mortality, moribundity, decreased body weight and food consumption in the adult rats, indicating severe maternal toxicity. No adverse effects were observed on reproductive performance or organs, but hypertrophy/hyperplasia in the thyroid gland, changes in thyroid hormone concentrations, litter loss, and dystocia were observed. Lower mean pup weights were also observed in high-dose group. Based on this study, the No Observed Adverse Effect Levels (NOAELs) for CBD were determined.