COMT Genetic Variants and BDNF Level Associations with Cannabinoid Plasma Exposure: A Preliminary Study

: Cannabis sativa L. shows potent anti-inflammatory activity, resulting in an interesting pharmacological option for pain management. The aim of the study was to evaluate the association between pharmacogenetics, neurological and inflammatory biomarkers, and cannabinoid plasma exposure in patients treated with cannabis. A total of 58 patients with a diagnosis of neuropathic and chronic pain treated with medical cannabis were analyzed. Cannabis was administered as a decoction (n = 47) and as inhaled cannabis (n = 11): 30 patients were treated with cannabis with high THC, while 28 patients were treated with cannabis with reduced THC (plus CBD). Cannabinoid plasma concentrations were obtained with UHPLC-MS/MS. Allelic discrimination was assessed by real-time PCR. Inflammation biomarkers (e.g., interleukin-10) were analyzed by ELISA, neurofilaments light chain (NFL), and brain-derived neurotrophic factor (BDNF) by Single Molecule Array. A statistically significant difference in IL-10 (p = 0.009) and BDNF (p = 0.004) levels was observed comparing patients treated with decoction and inhaled cannabis. BDNF and NFL results correlated with cannabinoid concentrations. Concerning genetics, the COMT 680 T>C genetic variant influences cannabinoid plasma levels, including Δ9-THC (p = 0.017). Conclusions: This study shows a possible impact of some genetic variants on cannabinoid plasma exposure, other than a possible role of medical cannabis on inflammation-related and neuronal impairment factor levels. Further studies in larger cohorts are required.