The opioid system in substance-use disorder treatment

There are several unmet needs in translating the current understanding of the endogenous opioid system into treatments for addiction.^[5]

• Fuller exploration of the genetics of opioid-use disorder – whilst opioid-use disorder appears to some extent heritable, there are remarkably few genome-wide studies into the disorder.
• A better understanding of the interaction of opioid drugs with the brain – more research is needed in humans, rather than in animal models wherein the complexity of comorbidity can be overlooked.
• Integration of animal and human models – comparing human data, including post mortem, with animal studies may enhance the reliability of preclinical models.
• Better understanding of the function of the endogenous opioid system – the endogenous opioid system is a complex interconnected network of different peptides and receptors, which interact with other neurochemical systems. Understanding this complexity is key to moving forward with precision treatments for opioid-use disorder, and other addictions.

Reference:
[1] Noble F, Lenoir M, Marie N. The opioid receptors as targets for drug abuse medication. Br J Pharmacol 2015; 172 (16): 3964–3979.

[2] Shippenberg TS, LeFevour A, Chefer VI. Targeting endogenous mu- and delta-opioid receptor systems for the treatment of drug addiction. CNS Neurol Disord Drug Targets 2008; 7 (5): 442–453.

[3] Norman H, D’Souza MS. Endogenous opioid system: a promising target for future smoking cessation medications. Psychopharmacology (Berl) 2017; 234 (9–10): 1371–1394.

[4] Miller PM (ed). Opioids Neuroimaging. In: Miller PM (ed). Biological Research on Addiction: Comprehensive Addictive Behaviors and Disorders, volume 2. Elsevier, 2013.

[5] Emery MA, Akil H. Endogenous opioids at the intersection of opioid addiction, pain, and depression: the search for a precision medicine approach. Annu Rev Neurosci 2020; 43: 355–374.