Endocannabinoid involvement in reward and impulsivity in addiction

Addiction is one of the most disabling diseases in the world. An important neurotransmitter system that has recently been implicated in addiction is the endocannabinoid system. The endocannabinoid system consists of cannabinoid receptors and endocannabinoid ligands that work on these receptors. Animal studies have shown that blocking the cannabinoid system prevents relapse to addiction, while activating the cannabinoid system with an agonist evokes relapse. Still, the involvement of the endocannabinoid system in addiction in humans remains unclear. The current thesis aimed to clarify the role of the endocannabinoid system in reward processing in nicotine addiction in humans. Brain function during reward processing was assessed using functional Magnetic Resonance Imaging (fMRI). In the first study described in this thesis, we have shown that both chronic nicotine and cannabis use attenuates reward-related brain activity in the nucleus accumbens, a brain area well known for its involvement in reward processing. Next, the endocannabinoid system was challenged using the partial cannabinoid agonist THC, the main psychoactive constituent of cannabis. When comparing nicotine users with non-using controls, we showed that a THC challenge did not affect reward processing in the nucleus accumbens in controls, while it was attenuated in nicotine users. Thus, altered reward processing as is found in nicotine addiction is associated with increased sensitivity of the cannabinoid system. In contrast, the endocannabinoid system seems to play a limited role in normal reward processing. Together, these data indicate that the endocannabinoid system is involved in addiction, and possibly other diseases in which reward processing is impaired, such as depression and ADHD