(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.