Dysregulation of the endogenous cannabinoid system following opioid exposure

Rates of opioid-related deaths and overdoses in the United States are at record-high levels. Thus, novel neuro-biological targets for the treatment of OUD are greatly needed. Given the close interaction between the endogenous opioid system and the endocannabinoid system (ECS), targeting the ECS may have therapeutic potential in OUD. The various components of the ECS, including cannabinoid receptors, their lipid-derived endogenous ligands (endocannabinoids [eCBs]), and the related enzymes, present potential targets for devel-oping new medications in OUD treatment. The purpose of this paper is to review the clinical and preclinical literature on the dysregulation of the ECS after exposure to opioids. We review the evidence of ECS dysregulation across various study types, exposure protocols, and measurement protocols and summarize the evidence for dysregulation of ECS components at specific brain regions. Preclinical research has shown that opioids disrupt various ECS components that are region-specific. However, the results in the literature are highly heterogenous and sometimes contradictory, possibly due to variety of different methods used. Further research is needed before a confident conclusion could be made on how exposure to opioids can affect ECS components in various brain regions.

Automated summary

This paper reviews the clinical and preclinical literature on the dysregulation of the endocannabinoid system (ECS) after exposure to opioids. The results show that opioids disrupt various ECS components in specific brain regions. However, the literature results are heterogeneous and contradictory, suggesting the need for further research to determine the effects of opioids on ECS components in different brain regions.