Female Mice Developed Greater THC Tolerance Than Males, Especially With HIV

Chronic THC history (90 days) led to tolerance across behavioral measures, reducing THC-induced hypothermia, pain relief, and sedation, especially in females. An acute THC challenge increased anxiety-like behavior specifically in females with chronic THC history. HIV-transgenic mice showed genotype-dependent effects, with high microglial-CCL3 co-occurrence in sex-specific brain regions.

HIV-1 Tg26 transgenic and control mice received 3 mg/kg THC or vehicle for 90 days (5 days/week). After a 7-day washout, all received a 10 mg/kg acute THC challenge. Behavioral, neuroinflammatory, and THC metabolite measures were assessed.

This study reveals important sex differences in THC tolerance development that have clinical implications for both recreational and medical cannabis users. The interaction with HIV status is particularly relevant given that cannabis is commonly used among people living with HIV.

Sex differences in cannabis tolerance have been suggested by human studies but are difficult to study rigorously. This controlled animal model confirms that females develop tolerance differently and may experience different consequences of chronic use, especially when combined with HIV.

Mouse model, and the Tg26 HIV model does not perfectly replicate human HIV infection. The 90-day chronic exposure may not mirror typical human use patterns. Small sample sizes per group.