Alessandra Manca, Cristina Valz, Francesco Chiara, Alice Palermiti, Jacopo Mula, Sara Soloperto, Miriam Antonucci, Amedeo De Nicolò, Nicola Luxardo, Daniele Imperiale, Flavio Vischia, David De Cori, Jessica Cusato, Antonio D'Avolio
{"title":"COMT遗传变异和BDNF水平与大麻素血浆暴露的关系:初步研究。","authors":"Alessandra Manca, Cristina Valz, Francesco Chiara, Alice Palermiti, Jacopo Mula, Sara Soloperto, Miriam Antonucci, Amedeo De Nicolò, Nicola Luxardo, Daniele Imperiale, Flavio Vischia, David De Cori, Jessica Cusato, Antonio D'Avolio","doi":"10.3390/jox15030066","DOIUrl":null,"url":null,"abstract":"<p><p><i>Cannabis sativa</i> 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 (<i>p</i> = 0.009) and BDNF (<i>p</i> = 0.004) levels was observed comparing patients treated with decoction and inhaled cannabis. BDNF and NFL results correlated with cannabinoid concentrations. Concerning genetics, the <i>COMT</i> 680 T>C genetic variant influences cannabinoid plasma levels, including Δ9-THC (<i>p</i> = 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.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 3","pages":""},"PeriodicalIF":6.8000,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101174/pdf/","citationCount":"0","resultStr":"{\"title\":\"<i>COMT</i> Genetic Variants and BDNF Level Associations with Cannabinoid Plasma Exposure: A Preliminary Study.\",\"authors\":\"Alessandra Manca, Cristina Valz, Francesco Chiara, Alice Palermiti, Jacopo Mula, Sara Soloperto, Miriam Antonucci, Amedeo De Nicolò, Nicola Luxardo, Daniele Imperiale, Flavio Vischia, David De Cori, Jessica Cusato, Antonio D'Avolio\",\"doi\":\"10.3390/jox15030066\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><i>Cannabis sativa</i> 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 (<i>p</i> = 0.009) and BDNF (<i>p</i> = 0.004) levels was observed comparing patients treated with decoction and inhaled cannabis. BDNF and NFL results correlated with cannabinoid concentrations. Concerning genetics, the <i>COMT</i> 680 T>C genetic variant influences cannabinoid plasma levels, including Δ9-THC (<i>p</i> = 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.</p>\",\"PeriodicalId\":42356,\"journal\":{\"name\":\"Journal of Xenobiotics\",\"volume\":\"15 3\",\"pages\":\"\"},\"PeriodicalIF\":6.8000,\"publicationDate\":\"2025-05-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101174/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Xenobiotics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3390/jox15030066\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Xenobiotics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/jox15030066","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"TOXICOLOGY","Score":null,"Total":0}
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.
期刊介绍:
The Journal of Xenobiotics publishes original studies concerning the beneficial (pharmacology) and detrimental effects (toxicology) of xenobiotics in all organisms. A xenobiotic (“stranger to life”) is defined as a chemical that is not usually found at significant concentrations or expected to reside for long periods in organisms. In addition to man-made chemicals, natural products could also be of interest if they have potent biological properties, special medicinal properties or that a given organism is at risk of exposure in the environment. Topics dealing with abiotic- and biotic-based transformations in various media (xenobiochemistry) and environmental toxicology are also of interest. Areas of interests include the identification of key physical and chemical properties of molecules that predict biological effects and persistence in the environment; the molecular mode of action of xenobiotics; biochemical and physiological interactions leading to change in organism health; pathophysiological interactions of natural and synthetic chemicals; development of biochemical indicators including new “-omics” approaches to identify biomarkers of exposure or effects for xenobiotics.