Healthy Sleep, Orexin System and Addiction

Abstract

Introduction: sleep disturbances are often reported in the context of depression, anxiety, and substance abuse disorder, observations that have strengthened the idea that there is an underlying link between them. Recently, the orexinergic system has been proposed as a possible common regulator, as orexinergic innervation reaches both sleep and wake-promoting centers and the mesolimbic pathway, potentially allowing orexinergic stimuli to promote wakefulness and addiction concurrently. Objective: to describe the involvement of the orexinergic system in behaviors such as sleep and substance abuse disorders, and the therapeutical potential of orexin modulators for the treatment of such conditions. Method: a search in scientific databases (PubMed, Scopus and Science Direct) was carried out for information regarding sleep, the orexinergic system, and substance abuse disorders. Information regarding clinical trials for orexin modulators was extracted from the clinicaltrials.gov website and the International Standard Randomized Controlled Trial Number (ISRCTN) registry. Results: experimental evidence suggests that orexinergic hyperactivity can lead to insomnia and increase drug-seeking behavior. Therefore, orexin modulators are being tested for their potential as aid in the treatment of substance abuse disorders with alcohol, nicotine, and opioids, leading the ongoing clinical trials. Discussion and conclusions: substance abuse disorders are often accompanied by sleep disturbances, a relationship that has been proved to be a risk factor for relapse. In this regard, orexinergic antagonists reduce the activity of the orexinergic system in humans, increasing sleep quality and potentially reducing the intensity of withdrawal symptoms. Therefore, the orexinergic system could function as the proposed link between sleep and issues such as substance abuse, anxiety, and depression.