Studies that provide mechanistic evidence delineating how the enhancement of the risk of psychosis by cannabis may be mediated at the neural level in humans are important. The modulatory effects of tetrahydrocannabinol (THC) on medial temporal, anterior cingulate/medial prefrontal and striatal activation during verbal learning were observed in the absence of differential task performance between the drug conditions. This chapter summarizes the evidence from studies that have examined the acute neural effects of cannabis and its main psychoactive ingredients during cognitive tasks, as well as on resting state activity of the brain. The acute effects of cannabis on neural activity during cognitive processing paradigms apart from learning have been examined by few other studies. Studies are underway that aim to provide mechanistic insights into the genetic modulation of the acute symptomatic, cognitive and neural effects of cannabis in humans.