Sleep: The components of the endocannabinoid system change in concentration based on circadian rhythm, the main driver of the human sleep-wake cycle. Animal experiments show that both AEA and 2-AG promote sleep via CB1, with AEA doing this by increasing adenosine levels and 2-AG by increasing the melanin-concentrating hormone. Human studies of the effect of exogenous cannabinoids are more mixed, but there is some evidence of sleep promotion. Cognition: THC intoxication has been found to decrease a number of higher cognitive functions, including memory, attention, executive function, learning global function, and decision-making. The ECS has been found to promote activation and prevent deactivation of the default mode network. THC is capable of reducing connectivity in the salience network, affecting attention. It also causes diminished capacity for error awareness has been linked to clinical symptoms of delusions and loss of insight. A SNP in the gene encoding a CB1 receptor, rs2023239, resulting in increased activity, is associated with higher impulsivity in ADHD patients and is also associated with Tourette’s syndrome. A large systemic review of acute versus chronic effects of cannabis on cognition found that not only did alterations on cognition decrease with repeated exposures but that the development of tolerance in the domain of cognition was highest of all other systems. Neuroprotection: Simply by nature of its typical feedback inhibition function, the endocannabinoid system is ideally suited for neuroprotection. 2-AG was found to be neuroprotective for brain injury in mice with findings of decreased brain edema, reduced infarct volume, and decreased hippocampal cell death, as well as better clinical recovery when administered after injury. In experimental models of Alzheimer’s disease (AD) in mice, AEA is capable of reducing its cytotoxic effects and reduces GSK3 beta activity and inflammation. Migraines are currently thought to originate via a phenomenon called cortical spreading depression. Suppression of this phenomenon has been shown clinically with activation of CB1 receptor in rat brains. Lower levels of AEA have been found in the CSF of patients with chronic migraines. Activation of the ECS can also decrease seizure activity.