Perinatal exposure to Delta-9-tetrahydrocannabinol (THC) induces apoptosis in the fetal thymus

Marijuana, or Cannabis sativa, is one of the most widely used drugs of abuse world-wide. Previous studies from our laboratory have shown that THC, the major psy-choactive component of marijuana, induces immunosuppression by triggering apoptosis in the thymus and the spleen. However, very little is known about the effects of THC on the fetal immune system development and homeostasis. In this study, we treated pregnant mice with THC on day 16 of gestation, which corresponded to the beginning of fetal T cell development, and found that the treatment resulted in a dose- and time-dependent decrease in fetal thymic cellularity. This correlated with an increase in the level of apoptosis, as demonstrated by TUNEL staining and cleavage of caspase-3 and 7. In addition, we found that THC induced apoptosis through both the cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), as its effects could be blocked by both CB1- and CB2-inhibitors in vivo. Finally, we found that perinatal exposure to THC resulted in a transient decrease in the percentage of double-positive T cells found in the fetal thymus. Together, these data suggest that perinatal exposure to THC can have a profound effect on the development of T cells in the fetus leading to immunosuppression, which bears tremendous implications for mothers abusing marijuana during pregnancy