Synergistic Pain-Reducing Effects of Bixa orellana (Chronic® and Chronic In®) and Cannabidiol-Rich Cannabis sativa Extracts in Experimental Pain Models

<b>Background:</b> The present study aimed to evaluate the potential synergy between pharmaceutical formulations containing <i>Bixa orellana</i> L. (granulated-CHR OR and injectable nanodispersion-CHR IN) in conjunction with a cannabidiol (CBD)-rich extract of <i>Cannabis sativa</i> L. (CSE) on experimental pain models in Wistar rats. <b>Methods:</b> Chemical analysis was performed using gas chromatography (GC-MS). The pain tests employed were acetic acid-induced writhing (injection i.p. of 0.9% acetic acid), formalin (solution 1%), hot plate (55 ± 0.5 °C), and cold-water tail withdrawal tests. <b>Results:</b> Chemical analyses by chromatography confirmed that the oil from <i>B. orellana</i> is rich in δ-tocotrienol (72.0 ± 1.0%), while the oil from <i>Cannabis sativa</i> highlighted the presence of cannabidiol (CBD). The results from the experimental pain tests indicated that the combined administration of formulations containing <i>Bixa orellana</i> and <i>C. sativa</i>, such as the granulated CHR OR (400 mg/kg, orally) with CSE (40 mg/kg, orally) or the nanodispersion CHR IN (10 mg/kg, intramuscularly) with CSE (40 mg/kg, orally), demonstrated significant results (<i>p</i> < 0.001) in pain reduction. Although the formulations containing <i>Bixa orellana</i> extract showed statistical significance in the tests when used in isolation, their effects were inferior compared to the combined use with CSE or the isolated use of CSE. These findings suggest that combining formulations containing extracts of these plant species may represent a viable therapeutic option, considering the synergistic action in reducing pain under the experimental conditions employed. <b>Conclusions:</b> these results imply that combining the phytocomplexes present in <i>B. orellana</i> and <i>C. sativa</i> may be a promising approach for pain treatment.