Barriers and Breakthroughs in Targeting the Oxytocin System to Treat Alcohol Use Disorder

Abstract

Development of better treatments for alcohol use disorder (AUD) is urgently needed. One promising opportunity for this development is the potential of targeting the oxytocin peptide system. Preclinical studies showed that administration of exogenous oxytocin or, more recently, stimulation of neurons expressing endogenous oxytocin lead to a decreased alcohol consumption across several rodent models. Initial clinical studies also showed that administration of oxytocin decreased craving for alcohol and heavy alcohol drinking. However, several more recent clinical studies were not able to replicate these effects. Thus, although targeting the oxytocin system holds promise for the treatment of AUD, more nuanced approaches toward development and application of these treatments are needed. In this mini-review we discuss potential caveats resulting in differential success of attempts to use oxytocin for modulating alcohol use disorder-related behaviors in clinical studies and evaluate three directions in which targeting the oxytocin system could be improved: (1) increasing potency of exogenously administered oxytocin, (2) developing oxytocin receptor agonists, and (3) stimulating components of the endogenous oxytocin system. Both advances and potential pitfalls of these directions are discussed.

Oxytocin: An expansive review of its mechanisms, functions, and therapeutic potential

“…Preclinical studies have shown that oxytocin attenuates drug-seeking behaviors and reduces drug reward in animal models of addiction [64]. Studies have explored the use of oxytocin in the treatment of alcohol, cocaine, heroin, and opioid dependence, with some evidence suggesting reductions in drug cravings and relapse rates [65,66,67].…”

Off-label and investigational drugs in the treatment of alcohol use disorder: A critical review

“…A reduction of craving and alcohol consumption may only be detectable shortly after oxytocin administration, as suggested by one rodent study ( Stevenson et al, 2017 ). Despite these failures, oxytocin may still have considerable potential in the treatment of alcohol use disorder if pharmacokinetic problems can be solved ( Ryabinin and Zhang, 2022 ), or if oxytocin could find use as an “as needed” medication for rapid reduction of alcohol consumption.…”