Complex pharmacology of natural cannabinoids: evidence for partial agonist activity of delta9-tetrahydrocannabinol and antagonist activity of cannabidiol on rat brain cannabinoid receptors

Life Sci. 1998;63(1):PL1-6. doi: 10.1016/s0024-3205(98)00238-0.

Abstract

Delta9-tetrahydrocannabinol (delta9-THC), cannabinol and cannabidiol are three important natural cannabinoids from the Marijuana plant (Cannabis sativa). Using [35S]GTP-gamma-S binding on rat cerebellar homogenate as an index of cannabinoid receptor activation we show that: delta9-THC does not induce the maximal effect obtained by classical cannabinoid receptor agonists such as CP55940. Moreover at high concentration delta9-THC exhibits antagonist properties. Cannabinol is a weak agonist on rat cerebellar cannabinoid receptors and cannabidiol behaves as an antagonist acting in the micromolar range.

MeSH terms

  • Analgesics / pharmacology
  • Animals
  • Binding, Competitive / drug effects
  • Brain / drug effects*
  • Brain / metabolism
  • Cannabidiol / pharmacology*
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cerebellar Cortex / drug effects
  • Cyclohexanols / pharmacology
  • Dronabinol / pharmacology*
  • Guanosine Triphosphate / metabolism
  • Male
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cannabinoid
  • Receptors, Drug / agonists*
  • Receptors, Drug / antagonists & inhibitors*
  • Receptors, Drug / metabolism
  • Rimonabant

Substances

  • Analgesics
  • Cyclohexanols
  • Piperidines
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Cannabidiol
  • Dronabinol
  • 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
  • Guanosine Triphosphate
  • Rimonabant