Modulation of free intracellular calcium and cAMP by morphine and cannabinoids, alone and in combination in mouse brain and spinal cord synaptosomes

Pharmacol Biochem Behav. 1994 Dec;49(4):1093-100. doi: 10.1016/0091-3057(94)90270-4.


Changes in [Ca++]i and cAMP were evaluated as possible mechanisms by which the cannabinoids enhance the antinociception of morphine. The addition of subactive concentrations of delta 9-(THC) and morphine in combination to brain synaptosomes did not result in an enhanced decrease in [Ca++]i; however, this drug combination enhanced decreases in [Ca++]i in spinal cord synaptosomes. The combination of CP55,940 and morphine produced enhanced decreases in [Ca++]i in both brain and spinal cord synaptosomes. In brain synaptosomes, the combination of delta 9-THC and morphine produced an additive decrease in cAMP accumulation, whereas no significant change was observed with this combination in the spinal cord. Thus, the difference in the modulation of [Ca++]i but not cAMP in the brain in vitro may be a predictor of the greater-than-additive antinociceptive effects observe in vivo.

Publication types

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

MeSH terms

  • Animals
  • Brain Chemistry / drug effects*
  • Calcium / metabolism*
  • Cannabinoids / pharmacology*
  • Cyclic AMP / metabolism*
  • Cyclohexanols / pharmacology
  • Dronabinol / pharmacology
  • Drug Interactions
  • In Vitro Techniques
  • Mice
  • Morphine / pharmacology*
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism*
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism*


  • Cannabinoids
  • Cyclohexanols
  • Morphine
  • Dronabinol
  • 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
  • Cyclic AMP
  • Calcium