Differential Effect of Abusing Substances Alone or in Combination in Systemic Inflammation

Background and Objectives: This study aims to compare, for the first time, the impact of different substances detected by immunoassay, either alone or in combination, in the values of neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic inflammation in a large series of cases. Materials and Methods: Patients with immunoassay urine tests positive for at least one of the following substances of abuse: cannabis, cocaine, amphetamine or opioids, from January 2021 to December 2025 at the Doctor Negrín University Hospital Laboratory were included in this study. A complete blood count, including leukocyte differential count, performed at the time of the substance detection urine analysis, was mandatory. Results: A total of 5008 samples were included in the present study. Cannabis alone was detected in 1831 cases, showing lower NLR (median 2.39) than cocaine (1055 cases, median: 2.44), opioids (227 cases, median: 3.01) and amphetamine/methamphetamine (487 cases, median: 3.28) (p < 0.0001). The detection of combined substances increased the NLR (p < 0.0001) mainly in combinations including amphetamines. In a lineal regression analysis, age (p < 0.0001), sex (p = 0.012) and substance consumption pattern (p < 0.0001) were independent predictors of NLR values. Conclusions: Our study demonstrated for the first time that the inflammatory effects of cannabis, cocaine, opioids and amphetamine/methamphetamine differ significantly, with amphetamine/methamphetamine and opioids being related to the highest NLR values. We also analyzed, for the first time, in the largest patient series studied, how the concomitant detection of different patterns of substances of abuse affects systemic inflammation patterns. The first finding is that an increase in the number of substances detected increases the NLR values. The second finding is that combinations including amphetamine/methamphetamine showed the highest inflammation marker (NLR) values.