*Article* **Combinations of Cannabidiol and Δ9-Tetrahydrocannabinol in Reducing Chemotherapeutic Induced Neuropathic Pain**

**Diana E. Sepulveda 1,2, Kent E. Vrana 1, Nicholas M. Graziane 1,2,\* and Wesley M. Raup-Konsavage 1,\***


**\***Correspondence: ngraziane@pennstatehealth.psu.edu (N.M.G.); wkonsavage@pennstatehealth.psu.edu (W.M.R.-K.); Tel.: +717-531-8433 (N.M.G.); +717-531-4172 (W.M.R.-K.)

**Abstract:** Neuropathic pain is a condition that impacts a substantial portion of the population and is expected to affect a larger percentage in the future. This type of pain is poorly managed by current therapies, including opioids and NSAIDS, and novel approaches are needed. We used a cisplatin-induced model of neuropathic pain in mice to assess the effects of the cannabinoids THC and CBD alone or in varying ratios as anti-nociceptive agents. In addition to testing pure compounds, we also tested extracts containing high THC or CBD at the same ratios. We found that pure CBD had little impact on mechanical hypersensitivity, whereas THC reduced mechanical hypersensitivity in both male and female mice (as has been reported in the literature). Interestingly, we found that high CBD cannabis extract, at the same CBD dose as pure CBD, was able to reduce mechanical hypersensitivity, although not to the same level as high THC extract. These data sugges<sup>t</sup> that, at least for CBD-dominant cannabis extracts, there is an increase in the anti-nociceptive activity that may be attributed to other constitutes of the plant. We also found that high THC extract or pure THC is the most efficacious treatment for reducing neuropathic pain in this model.

**Keywords:** neuropathic pain; tetrahydrocannabinol; cannabidiol; cannabinoids; cannabis
