Seeing through the smoke: Human and animal studies of cannabis use and endocannabinoid signalling in corticolimbic networks

- Corticolimbic circuits mediate cognitive and emotional behavioural processes.
- Endocannabinoid activity, and thus exogenous cannabinoids, modulate their function.
- The prefrontal cortex, amygdala and ventral hippocampus are key neural loci.
- Individual variation in cannabis response is an important consideration.
- Both human and animal studies are vital components of such research.

Public opinion surrounding the recreational use and therapeutic potential of cannabis is shifting. This review describes new work examining the behavioural and neural effects of cannabis and the endocannabinoid system, highlighting key regions within corticolimbic brain circuits. First, we consider the role of human genetic factors and cannabis strain chemotypic differences in contributing to interindividual variation in the response to cannabinoids, such as THC, and review studies demonstrating that THC-induced impairments in decision-making processes are mediated by actions at prefrontal CB1 receptors. We further describe evidence that signalling through prefrontal or ventral hippocampal CB1 receptors modulates mesolimbic dopamine activity, aberrations of which may contribute to emotional processing deficits in schizophrenia. Lastly, we review studies suggesting that endocannabinoid tone in the amygdala is a critical regulator of anxiety, and report new data showing that FAAH activity is integral to this response. Together, these findings underscore the importance of cannabinoid signalling in the regulation of cognitive and affective behaviours, and encourage further research given their social, political, and therapeutic implications.