V-067 | Oral Administration of THC:CBD formulations prevent pain-like behaviors without exacerbating paclitaxel-induced changes in weight, locomotion, and anxiety in a rat model of chemotherapy-induced neuropathy.

Cognition, Behavior, and Memory
Author: Delia Soriano | Email: soriano.del@gmail.com

Delia Soriano^1°4°, Milagros Argañarás^2°,Pablo Brumovsky^3°4°, Marcelo Villar^1°4°, Florencia Coronel^1°4°

^1° Laboratorio de Dolor en Cáncer, Instituto de Investigaciones en Medicina Traslacional CONICET – Universidad Austral, Buenos Aires, Argentina.
^2° Laboratorio de Inmuno-Endocrinología, Diabetes y Metabolismo, Instituto de Investigaciones en Medicina Traslacional CONICET – Universidad Austral, Buenos Aires, Argentina.
^3° Laboratorio de Mecanismos e Innovación Terapéutica en Dolor, Instituto de Investigaciones en Medicina Traslacional CONICET – Universidad Austral, Buenos Aires, Argentina.
^4° Facultad de Ciencias Biomédicas, Universidad Austral, Buenos Aires, Argentina.

Paclitaxel-induced neuropathy stands out as the primary, dose-limiting side effect of this extensively used chemotherapy agent. Effective preventive and therapeutic strategies are currently lacking. Our study aimed to assess the impact of oral administration of pharmaceutical-grade formulations containing the phytocannabinoids THC and CBD in a model of paclitaxel-induced neuropathy. The experimental design involved the co-administration of paclitaxel (PAX) and cannabinoid formulations (THC:CBD 1:1 and 1:20) to adult male rats. Mechanical and thermal sensitivity, locomotor activity, ethologically behaviors, anxiety-related parameters, feeding behaviors, and liver functionality were assessed. Daily administration of THC:CBD 1:1 prevented cold hypersensitivity and improved rearing behaviour, while THC:CBD 1:20 prevented PAX-induced thermal and mechanical allodynia. Cannabinoid formulations were not able to counteract hypo-locomotion, reduced vertical exploratory activity, increased anxious-like behaviors, attenuated weight gain, and decreased food and water intakes. However, the formulations employed did not induce further alterations or toxicity in animals receiving PAX. Consequently, our results suggest differential effects of two THC:CBD formulations on sensory function and spontaneous activities. Further studies are warranted to explore the mechanisms by which combinations of cannabinoids exert differential therapeutic effects on paclitaxel-induced neuropathy.