Cannabidiol potentiates pharmacological effects of Δ⁹-tetrahydrocannabinol via CB₁ receptor-dependent mechanism

Cannabidiol, a non-psychoactive component of cannabis, has been reported to have interactions with Δ⁹-tetrahydrocannabinol (Δ⁹-THC). However, such interactions have not sufficiently been clear and may have important implications for understanding the pharmacological effects of marijuana. In the present study, we investigated whether cannabidiol modulates the pharmacological effects of Δ⁹-THC on locomotor activity, catalepsy-like immobilisation, rectal temperature and spatial memory in the eight-arm radial maze task in mice. In addition, we measured expression level of cannabinoid CB₁ receptor at striatum, cortex, hippocampus and hypothalamus. Δ⁹-THC (1, 3, 6 and 10 mg/kg) induced hypoactivity, catalepsy-like immobilisation and hypothermia in a dose-dependent manner. In addition, Δ⁹-THC (1, 3 and 6 mg/kg) dose-dependently impaired spatial memory in eight-arm radial maze. On the other hand, cannabidiol (1, 3, 10, 25 and 50 mg/kg) did not affect locomotor activity, catalepsy-like immobilisation, rectal temperature and spatial memory on its own. However, higher dose of cannabidiol (10 or 50 mg/kg) exacerbated pharmacological effects of lower dose of Δ⁹-THC, such as hypoactivity, hypothermia and impairment of spatial memory. Moreover, cannabidiol (50 mg/kg) with Δ⁹-THC (1 mg/kg) enhanced the expression level of CB₁ receptor expression in hippocampus and hypothalamus. Cannabidiol potentiated pharmacological effects of Δ⁹-THC via CB₁ receptor-dependent mechanism. These findings may contribute in setting the basis for interaction of cannabinoids and to find a cannabinoid mechanism in central nervous system.