Cannabinoid inhibition of adenylate cyclase: relative activity of constituents and metabolites of marihuana

Neuropharmacology. 1987 May;26(5):507-12. doi: 10.1016/0028-3908(87)90035-9.


delta 9Tetrahydrocannabinol (THC) has been shown to inhibit the activity of adenylate cyclase in the N18TG2 clone of murine neuroblastoma cells. The concentration of delta 9THC exhibiting half-maximal inhibition was 500 nM. delta 8Tetrahydrocannabinol was less active, and cannabinol was only partially active. Cannabidiol, cannabigerol, cannabichromene, olivetol and compounds having a reduced length of the C3 alkyl side chain were inactive. The metabolites of delta 8THC and delta 9THC hydroxylated at the C11 position were more potent than the parent drugs. However, hydroxylation at the C8 position of the terpenoid ring resulted in loss of activity. Compounds hydroxylated along the C3 alkyl side chain were equally efficacious but less potent than delta 9THC. These findings are compared to the pharmacology of cannabinoids reported for psychological effects in humans and behavioral effects in a variety of animal models.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclase Inhibitors*
  • Animals
  • Behavior, Animal / drug effects
  • Cannabinoids / pharmacology*
  • Cell Line
  • Cell Membrane / enzymology
  • Chemical Phenomena
  • Chemistry
  • Dose-Response Relationship, Drug
  • Euphoria
  • Heart Rate / drug effects
  • Humans
  • Mice
  • Neurons / drug effects*
  • Species Specificity


  • Adenylyl Cyclase Inhibitors
  • Cannabinoids