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

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 suggest 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.

Three cannabis products attenuated oxaliplatin-induced peripheral neuropathy by inhibiting proteins that mediate oxaliplatin transport.

“…Considering that OXA is widely recommended for the treatment of solid tumors such as the rectum and breast 43 , There is an urgent need to nd drugs that can prevent and treat OIPN. Although previous studies have shown that CBD and THC can reduce peripheral nerve pain 7,27,29,[44][45][46][47] , the mechanism of action needs to be further explored. This time, we compared the protective effect of puri ed, broad-spectrum, and fullspectrum CBD on OXA-induced peripheral neuropathy and its relationship with platinum transport.…”

“…The application of CBD-rich phytocannabinoid extracts (64.5% CBD, 4% THC, 4% other cannabis components, and a small amount of terpenes and avonoids) can completely relieve thermal hyperalgesia, and the effect is signi cantly better than that of the CBD, THC, and THC + CBD groups, and the side effects are also less than those of the rst three groups. These results suggest that cannabinoid terpenoids and avonoids may have the ability to inhibit the metabolism of CBD and THC and improve the bioavailability of the drug, which con rms the synergistic effect of the active components of cannabinoids 28 .In 2022, Diana E. et al also showed that whole plant cannabis extract rich in high doses of CBD was more effective than THC and CBD alone in inhibiting the mechanical pain response induced by OXA in mice with peripheral neuropathy, which again con rmed that the internal components of whole plant cannabinoids synergistically played a more signi cant anti-peripheral nerve pain effect 29 . Therefore, whole plant cannabinoids may be an effective treatment for antagonism and prevention of OIPN.…”

Special Issue: Therapeutic Potential for Cannabis and Cannabinoids

“…Perhaps most importantly the study reports an overall increased quality of life in a treatment-resistant group of patients. Sepulveda et al found that pure THC, unlike pure CBD, is capable of reducing hyperalgesia in a murine model of chemotherapeutic-induced peripheral neuropathy [ 5 ]. This study also provides support for an “entourage” effect because a high CBD hemp extract, unlike the pure CBD, was able to reduce hyperalgesia when normalized to CBD levels; however, high THC extract and pure THC were found to offer the maximum reduction in sensitivity.…”

Secondary Terpenes in Cannabis sativa L.: Synthesis and Synergy

“…Furthermore, studies from our own group, using an animal model of chemotherapeutic induced peripheral neuropathy, demonstrated an enhanced effect at reducing mechanical hypersensitivity by an extract containing equal parts CBG and CBD, in addition to other cannabinoids and terpenes, compared to pure CBG [ 217 ]. Additionally, in the same animal model we found that pure CBD was without an effect; however, when animals were treated with a complex hemp extract at the same CBD concentration, a reduction in mechanical sensitivity was observed [ 218 ]. These studies suggest that there is a potential interaction between cannabinoids and terpenes that can enhance the effect of pure cannabinoids alone.…”