The highs and lows of cannabinoid receptor expression in disease: mechanisms and their therapeutic implications

Pharmacol Rev. 2011 Sep;63(3):461-70. doi: 10.1124/pr.110.003491. Epub 2011 Jul 13.


Alterations in the endogenous cannabinoid system have been described in almost every category of disease. These changes can alternatively be protective or maladaptive, such as producing antinociception in neuropathic pain or fibrogenesis in liver disease, making the system an attractive therapeutic target. However, the challenge remains to selectively target the site of disease while sparing other areas, particularly mood and cognitive centers of the brain. Identifying regional changes in cannabinoid receptor-1 and -2 (CB(1)R and CB(2)R) expression is particularly important when considering endocannabinoid system-based therapies, because regional increases in cannabinoid receptor expression have been shown to increase potency and efficacy of exogenous agonists at sites of disease. Although there have been extensive descriptive studies of cannabinoid receptor expression changes in disease, the underlying mechanisms are only just beginning to unfold. Understanding these mechanisms is important and potentially relevant to therapeutics. In diseases for which cannabinoid receptors are protective, knowledge of the mechanisms of receptor up-regulation could be used to design therapies to regionally increase receptor expression and thus increase efficacy of an agonist. Alternatively, inhibition of harmful cannabinoid up-regulation could be an attractive alternative to global antagonism of the system. Here we review current findings on the mechanisms of cannabinoid receptor regulation in disease and discuss their therapeutic implications.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cannabinoid Receptor Agonists
  • Cannabinoid Receptor Antagonists
  • Cannabinoid Receptor Modulators / agonists
  • Cannabinoid Receptor Modulators / antagonists & inhibitors
  • Cannabinoid Receptor Modulators / metabolism
  • Cannabinoids / agonists
  • Cannabinoids / antagonists & inhibitors
  • Cannabinoids / pharmacology
  • Gene Expression Regulation* / drug effects
  • Humans
  • Molecular Targeted Therapy
  • Nerve Tissue Proteins / agonists
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptor, Cannabinoid, CB2 / agonists
  • Receptor, Cannabinoid, CB2 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB2 / genetics
  • Receptor, Cannabinoid, CB2 / metabolism
  • Receptors, Cannabinoid / genetics
  • Receptors, Cannabinoid / metabolism*


  • Cannabinoid Receptor Agonists
  • Cannabinoid Receptor Antagonists
  • Cannabinoid Receptor Modulators
  • Cannabinoids
  • Nerve Tissue Proteins
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Receptors, Cannabinoid