Clonidine

Abstract

Abstract Clonidine’s molecular mechanism of action is agonism at the alpha-2A receptor, a subtype of the alpha-2-adrenergic receptor, found principally within the prefrontal cortex (PFC), where it prevents the secretion of norepinephrine (NE). NE causes the symptoms of withdrawal. Thus, clonidine can treat withdrawal-related symptoms including anxiety, hypertension, and tachycardia. Gold and associates found they could reverse the effects of locus coeruleus stimulation with clonidine. This noradrenergic hypothesis for opioid withdrawal changed the field. The benefits of clonidine in the transition to long-acting injectable naltrexone were confirmed in the 1980s for physicians, executives, and other motivated patients with Opioid Use Disorders (OUDs). Naltrexone, despite poor compliance, provides chronic opioid receptor blockade, prevents overdose, opioid intoxication, and subsequent re-addiction in recovered in motivated patients. The development of clonidine and naltrexone as treatment agents for OUD demonstrates that neurobiological advances could be translated from rodents to nonhuman primates to man into new effective clinical approaches.