Management of SCI Induced Chronic Pain in Rats Using Cannabidiol and β-caryophyllene

Amanda Pacheco-Spiewak
University of Miami

Anjalika Eeswara1, Suzanne C. Gross1, Daisha Ball1, Stanislava Jergova1, Jacqueline Sagen1
1University of Miami

Objective: Medical marijuana is often used to relieve pain, but there is a paucity of preclinical studies which evaluate the effects of cannabis components in chronic pain models. Spinal cord injuries (SCI) frequently result in chronic pain which may be significantly attenuated using marijuana and its medicinal extracts. The goal of this study was to evaluate the effects of two cannabis components, Cannabidiol (CBD) and β-caryophyllene (BCP), and their potentially synergistic pain-relieving combination.

Methods: Using male and female Sprague-Dawley rats, spinal cord injuries were induced using a clip compression model at mid-thoracic levels. To assess neuropathic pain symptoms, we evaluated the development of tactile allodynia, cold allodynia, and heat hyperalgesia. First, we conducted dose-response analyses for both drugs using a battery of behavioral tests including the Von Frey test, the acetone evaporation test, and the Hargreaves test. Rats were tested at baseline and every 30 minutes for 2 hours post-injection. If some analgesic effects remained, they were again tested at 5- and 24-hours post-drug administration. CBD was tested at 0.1-5 mg/kg (ip) and BCP was orally administered (oral gavage) at 10-50 mg/kg. We then assessed for potential synergism using isobolographic analysis based on ratios of the single drug A50 values.

Results: Both CBD and BCP administered individually reduced cold and tactile hypersensitivity in both male and female rats. The combination of CBD and BCP produced synergistic effects for cold allodynia in both male and female rats. Additive effects were observed in male rats for tactile allodynia. The effects of both compounds and the combination appeared less potent in females compared to males, suggesting that sex differences will need to be considered when developing cannabinoid pain-reducing strategies. We observed no overt side effects from combining CBD and BCP.

Conclusion: These findings support the further development of cannabis extracts as potentially safe and effective therapeutics in the management of chronic SCI pain.

Co-authors: Anjalika Eeswara1, Suzanne C. Gross1, Daisha Ball1, Stanislava Jergova1, Jacqueline Sagen1
1University of Miami

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