Intraperitoneal delivery of cannabidiol (CBD) and Δ⁹-tetrahydocannabinol (THC) promotes papillomavirus infections in athymic nude mice

We used our mouse papillomavirus (MmuPV1) model to test the hypothesis that two primary psychoactive ingredients of marijuana, Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD), promote papillomavirus persistence in the oral mucosa of infected mice. We conducted intraperitoneal (ip) injections of a moderate dose (3 mg/kg) of either CBD and/or THC in both male and female athymic nude mice and followed the mice up to 20 weeks post-infection. These doses are comparable to what is estimated for human conventional cannabis consumption. All mice were infected with MmuPV1 in the oral cavity at week 4 post-ip delivery of CBD, THC, or a combination of THC and CBD (T + C). THC and CBD were detected in the blood of treated mice for up to 72 h after ip injection. Significantly higher levels of viral DNA were detected in males from both CBD and T + C-treated groups compared to those in the control group at 9- 10-and 12-weeks post infection. A marginally increased viral RNA was also detected in the infected tongues of males in all tested groups compared to that in males in the vehicle control group; the opposite was observed in females. We detected significantly higher levels of dermal dendritic cells (CD205⁺CD11c⁺), granulocytes (Ly6G⁺), but macrophages (F4-80+) recruited to the infected tongues of CBD-treated females. Our findings suggest that CBD may play a role in promoting MmuPV1 persistence in the oral cavity.