Intrathecal Actions of the Cannabis Constituents Δ(9)-Tetrahydrocannabinol and Cannabidiol in a Mouse Neuropathic Pain Model

Int J Mol Sci. 2022 Aug 3;23(15):8649. doi: 10.3390/ijms23158649.


(1) Background: The psychoactive and non-psychoactive constituents of cannabis, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), synergistically reduce allodynia in various animal models of neuropathic pain. Unfortunately, THC-containing drugs also produce substantial side-effects when administered systemically. We examined the effectiveness of targeted spinal delivery of these cannabis constituents, alone and in combination. (2) Methods: The effect of acute intrathecal drug delivery on allodynia and common cannabinoid-like side-effects was examined in a mouse chronic constriction injury (CCI) model of neuropathic pain. (3) Results: intrathecal THC and CBD produced dose-dependent reductions in mechanical and cold allodynia. In a 1:1 combination, they synergistically reduced mechanical and cold allodynia, with a two-fold increase in potency compared to their predicted additive effect. Neither THC, CBD nor combination THC:CBD produced any cannabis-like side-effects at equivalent doses. The anti-allodynic effects of THC were abolished and partly reduced by cannabinoid CB1 and CB2 receptor antagonists AM281 and AM630, respectively. The anti-allodynic effects of CBD were partly reduced by AM630. (4) Conclusions: these findings indicate that intrathecal THC and CBD, individually and in combination, could provide a safe and effective treatment for nerve injury induced neuropathic pain.

Keywords: THC; cannabidiol; cannabinoid; intrathecal; mice; neuropathic pain; synergy.

MeSH terms

  • Analgesics / adverse effects
  • Animals
  • Cannabidiol* / adverse effects
  • Cannabinoid Receptor Agonists / pharmacology
  • Cannabinoids* / adverse effects
  • Cannabis*
  • Disease Models, Animal
  • Dronabinol / adverse effects
  • Hallucinogens* / adverse effects
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy
  • Mice
  • Neuralgia* / drug therapy


  • Analgesics
  • Cannabinoid Receptor Agonists
  • Cannabinoids
  • Hallucinogens
  • Cannabidiol
  • Dronabinol