Effects of cannabis on fetal development of rodents

The majority of teratologic studies on marihuana and Delta(9)-THC in rodents have been negative but serious observations of cleft palate in mice and eventrations in rabbits remain unexplained. There has been agreement on the increased incidence of in utero deaths. To clarify the potential effects of cannabinoids on fetal development, studies were performed in rodents using the inhalation and oral routes. The Delta(9)-THC doses in marihuana smoke were 0.8-3.8 mg/kg, which correlated with plasma Delta(9)-THC, levels of 73-297 ng/mL and carboxyhemoglobin levels between 21 and 60%. Oral Delta(9)-THC doses were 5-600 mg/kg for mice and 12-50 mg/kg for rats. An automatic inhalator provided a 50-mL puff from each of three NIDA cigarettes in a two-second puff retention of smoke for a 30-second exposure interval followed by a 30-second fresh air purge each min. Exposure to smoke was performed during days 6-15 of gestation. Oral studies included a similar treatment protocol but in addition the number of treatments and days of treatment were varied to establish the time of greatest effect on fetal development. The embryocidal effect of marihuana and Delta(9)-THC was demonstrated by two routes and in two rodent species. In fact, whole litter resorption was encountered and two to five treatments around days 7 to 9 of gestation were sufficient to induce embryotoxicity. At least in mice, the fetocidal effect appeared to be related to vaginal bleeding, possibly a consequence of interrupted development of fetoplacental circulation and deranged hormone balance. No drug-related teratogenic effects were found.