The most frequently reported use of
medical marijuana is for
pain relief. However, its psychoactive component Δ9-tetrahydrocannabinol (
THC) causes significant side effects.
Cannabidiol (CBD) and β-
caryophyllene (BCP), two other cannabis constituents, possess more benign side effect profiles and are also reported to reduce neuropathic and inflammatory
pain. We evaluated the
analgesic potential of CBD and BCP individually and in combination in a rat
spinal cord injury (SCI)
clip compression
chronic pain model. Individually, both phytocannabinoids produced dose-dependent reduction in tactile and
cold hypersensitivity in male and female rats with SCI. When co-administered at fixed ratios based on individual A50s, CBD and BCP produced enhanced dose-dependent reduction in allodynic responses with synergistic effects observed for
cold hypersensitivity in both sexes and additive effects for tactile
hypersensitivity in males. Antinociceptive effects of both individual and combined treatment were generally less robust in females than males. CBD:BCP co-administration also partially reduced
morphine-seeking behavior in a conditioned place preference (
CPP) test. Minimal cannabinoidergic side effects were observed with high doses of the combination. The antinociceptive effects of the CBD:BCP co-administration were not altered by either CB2 or μ-
opioid receptor antagonist pretreatment but, were nearly completely blocked by CB1 antagonist
AM251. Since neither CBD or BCP are thought to mediate antinociception via CB1 activity, these findings suggest a novel CB1 interactive mechanism between these two phytocannabinoids in the SCI
pain state. Together, these findings suggest that CBD:BCP co-administration may provide a safe and effective treatment option for the management of chronic SCI
pain.