There are sex differences in the progression of
drug addiction, relapse, and response to
therapies. Because
biological factors participate in these differences, they should be considered when using
biomarkers for addiction. In the current study, we evaluated the sex differences in psychiatric comorbidity and the concentrations of plasma mediators that have been reported to be affected by
cocaine. Fifty-five abstinent
cocaine-addicted subjects diagnosed with lifetime
cocaine use disorders (40 men and 15 women) and 73 healthy controls (48 men and 25 women) were clinically assessed with the diagnostic interview "Psychiatric Research Interview for Substance and
Mental Disorders." Plasma concentrations of
chemokines,
cytokines, N-acyl-
ethanolamines, and 2-acyl-glycerols were analyzed according to history of
cocaine addiction and sex, controlling for covariates age and body mass index (BMI). Relationships between these concentrations and variables related to
cocaine addiction were also analyzed in addicted subjects. The results showed that the concentrations of
chemokine (C-C motif) ligand 2/
monocyte chemotactic protein-1 (CCL2/MCP-1) and
chemokine (C-X-C motif) ligand 12/stromal cell-derived factor-1 (CXCL12/SDF-1) were only affected by history of
cocaine addiction. The plasma concentrations of
interleukin 1-beta (IL-1β),
IL-6,
IL-10, and
tumor necrosis factor-alpha (TNFα) were affected by history of
cocaine addiction and sex. In fact, whereas
cytokine concentrations were higher in control women relative to men, these concentrations were reduced in
cocaine-addicted women without changes in addicted men. Regarding
fatty acid derivatives, history of
cocaine addiction had a main effect on the concentration of each acyl derivative, whereas N-acyl-
ethanolamines were increased overall in the
cocaine group, 2-acyl-glycerols were decreased. Interestingly, N-palmitoleoyl-
ethanolamine (
POEA) was only increased in
cocaine-addicted women. The covariate BMI had a significant effect on
POEA and N-arachidonoyl-
ethanolamine concentrations. Regarding psychiatric comorbidity in the
cocaine group, women had lower incidence rates of comorbid
substance use disorders than did men. For example,
alcohol use disorders were found in 80% of men and 40% of women. In contrast, the addicted women had increased prevalences of comorbid
psychiatric disorders (i.e., mood, anxiety, and
psychosis disorders). Additionally,
cocaine-addicted subjects showed a relationship between the concentrations of N-stearoyl-
ethanolamine and
2-linoleoyl-glycerol and diagnosis of psychiatric comorbidity. These results demonstrate the existence of a sex influence on plasma
biomarkers for
cocaine addiction and on the presence of comorbid psychopathologies for clinical purposes.