Early oral administration of THC:CBD formulations prevent pain-related behaviors without exacerbating paclitaxel-induced changes in weight, locomotion, and anxiety in a rat model of chemotherapy-induced neuropathy

Abstract

Rationale Paclitaxel-induced neuropathy stands out as the primary, dose-limiting side effect of this extensively used chemotherapy agent. Prolonged hypersensitivity and pain represent the most severe clinical manifestations. Effective preventive and therapeutic strategies are currently lacking.Objectives Our study aimed to assess the impact of early oral administration of pharmaceutical-grade formulations containing the phytocannabinoids THC and CBD in a rat model of paclitaxel-induced neuropathy.Methods The experimental design involved the co-administration of paclitaxel and cannabinoid formulations with different THC to CBD ratios (THC:CBD 1:1 and THC:CBD 1:20) to adult male rats. Mechanical and thermal sensitivity, locomotor activity, vertical exploratory behaviors, anxiety-related parameters, weight gain, food and water consumption, and liver functionality were assessed.Results Daily administration of THC:CBD 1:1 successfully prevented paclitaxel-induced cold allodynia, while THC:CBD 1:20 effectively prevented both thermal and mechanical hypersensitivities. Additionally, THC:CBD 1:1 formulation restored rearing behavior, significantly reduced by paclitaxel. Conversely, neither cannabinoid formulation was able to counteract paclitaxel-induced hypo-locomotion, reduced vertical exploratory activity, increased anxiety-like behaviors, attenuatedweight gain, or decreased food and water intakes. However, the formulations employed did not induce further alterations or toxicity in animals receiving paclitaxel, and no signs of liver damage were detected.Conclusions Our results suggest a differential therapeutic effect of two THC:CBD formulations on pain-related behaviors and spontaneous activities, particularly in the context of peripheral neuropathy. These formulations represent a promising therapeutic strategy not only to managing pain but also for enhancing daily activities and improving the quality of life for cancer patients.