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<p>Cannabis (tetrahydrocannabinol, THC), benzodiazepines (BZO), and methamphetamine (MET) exert diverse pharmacodynamic effects on hepatic metabolism and immune signaling pathways. While experimental studies suggest that these agents modulate cytochrome P450 activity, oxidative stress pathways, and cytokine production, comparative clinical data particularly in African populations remain limited. This study investigated the association between single and polysubstance use and alterations in hepatic and inflammatory biomarkers. In a case–control design, 83 adults (19–59&#xa0;years) from Benin City, Nigeria, were categorized as controls (<i>n</i> = 20) or users of THC only (<i>n</i> = 27), THC/BZO (<i>n</i> = 12), THC/MET (<i>n</i> = 10), BZO/MET (<i>n</i> = 5), or THC/BZO/MET (<i>n</i> = 9). Substance exposure was confirmed by urine immunochromatographic screening. Plasma levels of aspartate aminotransferase (AST, U/L), alanine aminotransferase (ALT, U/L), alkaline phosphatase (ALP, U/L), gamma-glutamyl transferase (GGT, U/L), total bilirubin (mg/dL), direct bilirubin (mg/dL), interleukin-6 (IL-6, pg/mL), and interleukin-10 (IL-10, pg/mL) were measured using standardized biochemical and ELISA methods. Group differences were assessed using ANOVA with Bonferroni correction. AST levels were significantly elevated in the THC-only (79.07 ± 59.60 U/L) and THC/BZO (73.58 ± 46.11 U/L) groups compared with controls (36.90 ± 11.05 U/L; <i>p</i> = 0.002 and <i>p</i> = 0.027, respectively). ALT was higher in the THC/MET group (54.30 ± 51.15 U/L) versus controls (33.60 ± 12.31 U/L; <i>p</i> = 0.037). IL-6 concentrations were significantly reduced in THC-only, THC/BZO, and THC/BZO/MET users compared with controls (<i>p</i> = 0.002), an unexpected finding discussed further below, whereas IL-10 showed no significant intergroup differences. Cannabis, benzodiazepine, and methamphetamine exposure particularly in combination is associated with biochemical patterns consistent with subclinical hepatocellular and cholestatic stress, alongside selective modulation of IL-6–mediated inflammatory signaling. These findings support pharmacologically plausible interactions affecting hepatic metabolism and immune regulation and warrant longitudinal investigation to clarify mechanistic pathways and reversibility.</p>

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Impact of cannabis, benzodiazepines, and methamphetamine use on inflammatory and hepatic biomarkers in Benin City, Nigeria: a case–control study

  • 期刊论文

  • 发表日期：

    2026年5月25日

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  • Vani Onotinamhe Usman–Onoruvie,
  • Patricia Ejenawome Dele–Ochie,
  • Babatunde Ishola Gabriel Adejumo,
  • Fidelis Ohiremen Oyakhire,
  • Emmanuel Ojeideleko Akhaumere,
  • Uche Cletus Odionyenma,
  • Uchechukwu Dimkpa,
  • Basheer Madompoyil,
  • Odeh Betty Etinosa,
  • George Chibueze Aneke,
  • Usman Itakure Abdulkadir,
  • Grace Eleojo Obasuyi,
  • Feyisayo Olayemi Aiyesoro,
  • Samson Efenarhua,
  • Kelly Iria Esezobor,
  • Mathew Folaranmi Olaniyan,
  • Odekunle Bola Odegbemi

摘要

Cannabis (tetrahydrocannabinol, THC), benzodiazepines (BZO), and methamphetamine (MET) exert diverse pharmacodynamic effects on hepatic metabolism and immune signaling pathways. While experimental studies suggest that these agents modulate cytochrome P450 activity, oxidative stress pathways, and cytokine production, comparative clinical data particularly in African populations remain limited. This study investigated the association between single and polysubstance use and alterations in hepatic and inflammatory biomarkers. In a case–control design, 83 adults (19–59 years) from Benin City, Nigeria, were categorized as controls (n = 20) or users of THC only (n = 27), THC/BZO (n = 12), THC/MET (n = 10), BZO/MET (n = 5), or THC/BZO/MET (n = 9). Substance exposure was confirmed by urine immunochromatographic screening. Plasma levels of aspartate aminotransferase (AST, U/L), alanine aminotransferase (ALT, U/L), alkaline phosphatase (ALP, U/L), gamma-glutamyl transferase (GGT, U/L), total bilirubin (mg/dL), direct bilirubin (mg/dL), interleukin-6 (IL-6, pg/mL), and interleukin-10 (IL-10, pg/mL) were measured using standardized biochemical and ELISA methods. Group differences were assessed using ANOVA with Bonferroni correction. AST levels were significantly elevated in the THC-only (79.07 ± 59.60 U/L) and THC/BZO (73.58 ± 46.11 U/L) groups compared with controls (36.90 ± 11.05 U/L; p = 0.002 and p = 0.027, respectively). ALT was higher in the THC/MET group (54.30 ± 51.15 U/L) versus controls (33.60 ± 12.31 U/L; p = 0.037). IL-6 concentrations were significantly reduced in THC-only, THC/BZO, and THC/BZO/MET users compared with controls (p = 0.002), an unexpected finding discussed further below, whereas IL-10 showed no significant intergroup differences. Cannabis, benzodiazepine, and methamphetamine exposure particularly in combination is associated with biochemical patterns consistent with subclinical hepatocellular and cholestatic stress, alongside selective modulation of IL-6–mediated inflammatory signaling. These findings support pharmacologically plausible interactions affecting hepatic metabolism and immune regulation and warrant longitudinal investigation to clarify mechanistic pathways and reversibility.