Diabetic
peripheral neuropathy (
DPN) is characterized by progressive loss of peripheral nerves, which causes
numbness, weakness, and severe
pain. The medications available currently provide only modest relief from the
pain of
DPN and are associated with various side effects, which has generated an enormous demand for research on new therapeutic approaches. Dysregulation of the
endocannabinoid system has been reported in
DPN.
Cannabinoid-based medications have gained increasing attention as a potential
therapy to alleviate
DPN pain.
Endocannabinoids and
cannabinoids' actions are mediated primarily by
cannabinoid receptor 1 (CB1R) and
cannabinoid receptor 2 (CB2R).
Cannabinoids that activate CB1R have demonstrated a profound antinociceptive effect, although CB1R is associated with undesirable psychoactive effects. Peripherally restricted CB1R agonists help overcome this problem; however, adverse metabolic and cardiovascular effects limit its
therapeutic use. In contrast, CB1R antagonists, selective CB2R agonists, and
endocannabinoid metabolizing
enzymes inhibitors alleviate
DPN pain effectively with minimal side effects. This article provides a concise overview of the preclinical and clinical studies that have tested the therapeutic potential of targeting the
endocannabinoid system to treat painful
DPN.