Functional assessment of neuronal cannabinoid receptors in the muscular layers of human ileum and colon

Dig Liver Dis. 2002 Apr;34(4):262-9. doi: 10.1016/s1590-8658(02)80146-3.


Background & aims: The notion that specific receptors account for the ability of natural and synthetic cannabinoids to alter physiological functions, prompted this study aimed at assessing their functional presence in the human gut.

Methods: The effects have been studied of cannabinoids and selective antagonists of their receptors on chemically or electrically evoked contractions in preparations of human intestinal smooth muscle in vitro.

Results: Atropine prevented the contractions of longitudinal and circular muscle strips of ileum and colon induced by carbachol or electrical field stimulation; tetrodotoxin abolished only the latter which suggests they do involve activation of cholinergic neurons. The synthetic cannabinoid (+)WIN 55,212-2 had no effect on carbachol contractions, but in a concentration-dependent fashion prevented those elicited by electrical field stimulation - which were insensitive to the putative endogenous cannabinoid anandamide - more potently in longitudinal than in circular strips. The selective CB1 receptor antagonist SR141716, which had no effect in the absence of (+)WIN 55,212-2, competitively antagonised its inhibition of electrical field stimulation contractions, unlike the selective CB2 antagonist SR144528.

Conclusions: Cannabinoid CB1 receptors are functionally present in the human ileum and colon; their pharmacological activation apparently results in inhibition of excitatory cholinergic pathways subserving smooth muscle contraction.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Benzoxazines
  • Cannabinoids*
  • Colon / metabolism
  • Female
  • Gastrointestinal Motility / physiology*
  • Humans
  • Ileum / metabolism
  • Immunohistochemistry
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Morpholines / pharmacology
  • Muscle, Smooth / metabolism*
  • Naphthalenes / pharmacology
  • Receptors, Cannabinoid
  • Receptors, Drug / metabolism*


  • Benzoxazines
  • Cannabinoids
  • Morpholines
  • Naphthalenes
  • Receptors, Cannabinoid
  • Receptors, Drug
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone