Fatty acid binding protein 7 plays an important modulatory sex-dependent role on brain endocannabinoid levels and THC metabolism.

Fatty acid binding protein 7 (FABP7) is present in the brain, but its interaction with the endocannabinoid system and phytocannabinoids is still not well understood. FABP7 has been proposed as a shuttle protein for trafficking endogenous cannabinoids, as well as an intracellular carrier of THC. In a mouse model of FABP7 global deletion, we used ultra-high performance liquid chromatography- tandem mass spectrometry (UPLC-MS/MS) to measure brain levels of Δ9 tetrahydrocannabinol (THC) as well as its primary metabolite, 11-hydroxy-THC (11-OH-THC), in male and female mice after acute inhalation of THC, compared to wild-type controls. We also measured brain levels of endogenous cannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) both at baseline and after acute THC inhalation. We found that in females, brain concentrations of 11-OH-THC were significantly reduced in FABP7-/- mice compared to FABP7+/+. Additionally, FABP7-/- females had significantly reduced AEA levels and significantly increased 2-AG levels in brain tissue compared to FABP7+/+. Vaporized THC administration had trending, but not significant, impacts on endocannabinoid concentrations in both males and females. Our findings suggest a sex-specific role of FABP7 in the metabolism of THC as well as the regulation of endocannabinoid levels in the brain.