CANNABINOID TREATMENT OF MALE VS. FEMALE RATS WITH PERSISTENT HINDPAW INFLAMMATION
Britch, Stevie Christine
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Thirty-three states and the District of Columbia have enacted laws allowing for the use of medical marijuana, with an additional 13 states allowing for the use of medical marijuana that has low-to-no Δ9-tetrahydrocannabinol (THC) content, but high cannabidiol (CBD) content. Chronic pain is the most common reason for using medical marijuana. Chronic pain affects approximately 16 million people in the United States, and women are three times more likely than men to suffer from chronic pain. Previous studies suggest that THC may provide greater pain relief in females compared to males, yet reduce edema more in males than females. The goal of this dissertation research was to determine if the two major phytocannabinoids THC and CBD, given alone or together, are effective treatments for chronic inflammatory pain, particularly in females. First, the effects of acute vs. repeated THC or CBD exposure on inflammatory pain were examined in male and female rats (Ch. 2). THC dose-dependently reduced pain in both males and females with few sex differences, and little tolerance developed to THC’s effects. In contrast, CBD effects on inflammatory pain were minimal, whether administered acutely or repeatedly. Second, the effects of acute vs. repeated THC or CBD exposure on serum cytokines was examined in male and female rats with or without hindpaw inflammation (Ch. 3). THC did not alter serum cytokines, while CBD effects on serum cytokines were sex and pain-state dependent. Neither cannabinoid altered inflammatory cytokines in a manner that would indicate a therapeutically beneficial drug. Finally, CBD did not enhance THC effects on any assay (Ch. 4), suggesting that CBD-THC combinations may not be clinically beneficial for the treatment of inflammatory pain. There were several limitations, including timing of experiments, dosing, experimenter changes, and the model used. However, based off the present results, THC may be beneficial for the treatment of chronic inflammatory pain while having little impact on inflammatory cytokines. In contrast, CBD alone may not produce clinically meaningful pain relief and its immune-modulatory effects may result in significant unwanted side-effects. Furthermore, CBD may not enhance THC’s analgesia in chronic inflammatory pain.