The therapeutic role of cannabinoid receptors and its agonists or antagonists in Parkinson's disease

Prog Neuropsychopharmacol Biol Psychiatry. 2020 Jan 10;96:109745. doi: 10.1016/j.pnpbp.2019.109745. Epub 2019 Aug 20.

Abstract

Parkinson's disease (PD) is a neurodegenerative disease and its characteristic is the progressive degeneration of dopaminergic neurons within the substantia nigra (SN) of the midbrain. There is hardly any clinically proven efficient therapeutics for its cure in several recent preclinical advances proposed to treat PD. Recent studies have found that the endocannabinoid signaling system in particular the comprised two receptors, CB1 and CB2 receptors, has a significant regulatory function in basal ganglia and is involved in the pathogenesis of PD. Therefore, adding new insights into the biochemical interactions between cannabinoids and other signaling pathways may help develop new pharmacological strategies. Factors of the endocannabinoid system (ECS) are abundantly expressed in the neural circuits of basal ganglia, where they interact interactively with glutamatergic, γ-aminobutyric acid-ergic (GABAergic), and dopaminergic signaling systems. Although preclinical studies on PD are promising, the use of cannabinoids at the clinical level has not been thoroughly studied. In this review, we evaluated the available evidence and reviewed the involvement of ECS in etiologies, symptoms and treatments related to PD. Since CB1 and CB2 receptors are the two main receptors of endocannabinoids, we primarily put the focus on the therapeutic role of CB1 and CB2 receptors in PD. We will try to determine future research clues that will help understand the potential therapeutic benefits of the ECS in the treatment of PD, aiming to open up new strategies and ideas for the treatment of PD.

Keywords: CB1 receptors; CB2 receptors; Endocannabinoid system; Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arachidonic Acids / metabolism
  • Arachidonic Acids / therapeutic use
  • Cannabinoid Receptor Agonists / metabolism*
  • Cannabinoid Receptor Agonists / therapeutic use
  • Cannabinoid Receptor Antagonists / metabolism*
  • Cannabinoid Receptor Antagonists / therapeutic use
  • Cannabinoid Receptor Modulators / metabolism
  • Cannabinoid Receptor Modulators / therapeutic use
  • Cannabinoids / metabolism
  • Cannabinoids / therapeutic use
  • Capsaicin / analogs & derivatives
  • Capsaicin / metabolism
  • Capsaicin / therapeutic use
  • Endocannabinoids / metabolism
  • Endocannabinoids / therapeutic use
  • Humans
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / metabolism*
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Receptor, Cannabinoid, CB2 / agonists
  • Receptor, Cannabinoid, CB2 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB2 / metabolism*

Substances

  • Arachidonic Acids
  • Cannabinoid Receptor Agonists
  • Cannabinoid Receptor Antagonists
  • Cannabinoid Receptor Modulators
  • Cannabinoids
  • Endocannabinoids
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • arachidonyl-2-chloroethylamide
  • capsazepine
  • Capsaicin