title: Evaluation of plasma-free endocannabinoids and their congeners in abstinent cocaine addicts seeking outpatient treatment: impact of psychiatric co-morbidity.
abstract: Cocaine is associated with serious health problems including psychiatric co-morbidity. There is a need for the identification of biomarkers for the stratification of cocaine-addicted subjects. Several studies have evaluated circulating endocannabinoid-related lipids as biomarkers of inflammatory, metabolic and mental disorders. However, little is known in substance use disorders. This study characterizes both free N-acyl-ethanolamines (NAEs) and 2-acyl-glycerols in abstinent cocaine addicts from outpatient treatment programs who were diagnosed with cocaine use disorder (CUD; n = 88), and age-/gender-/body mass-matched healthy control volunteers (n = 46). Substance and mental disorders that commonly occur with substance abuse were assessed by the semi-structured interview 'Psychiatric Research Interview for Substance and Mental Diseases' according to the 'Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision' (DSM-IV-TR) and plasma-free acyl derivatives were quantified by a liquid chromatography-tandem mass spectrometry system. The results indicate that plasma acyl derivatives are altered in abstinent cocaine-addicted subjects with CUD (CUD subjects). While NAEs were found to be increased, 2-acyl-glycerols were decreased in CUD subjects compared with controls. Multivariate predictive models based on these lipids as explanatory variables were developed to distinguish CUD subjects from controls providing high discriminatory power. However, these alterations were not influenced by the DSM-IV-TR criteria for cocaine abuse and dependence as cocaine trait severity measure. In contrast, we observed that some free acyl derivatives in CUD subjects were found to be affected by the diagnosis of some co-morbid psychiatric disorders. Thus, we found that the monounsaturated NAEs were significantly elevated in CUD subjects diagnosed with mood [N-oleoyl-ethanolamine and N-palmitoleoyl-ethanolamine (POEA)] and anxiety (POEA) disorders compared with non-co-morbid CUD subjects. Interestingly, the coexistence of alcohol use disorders did not influence the circulating levels of these free acyl derivatives. In summary, we have identified plasma-free acyl derivatives that might serve as reliable biomarkers for CUD. Furthermore, we found that monounsaturated NAE levels are also enhanced by co-morbid mood and anxiety disorders in cocaine addicts. These findings open the way for the development of new strategies for cocaine addiction diagnosis and treatment.
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Pavón
authors.forename: Pedro
authors.initials: P
authors.lastname: Araos
authors.forename: Antoni
authors.initials: A
authors.lastname: Pastor
authors.forename: Montserrat
authors.initials: M
authors.lastname: Calado
authors.forename: María
authors.initials: M
authors.lastname: Pedraz
authors.forename: Rafael
authors.initials: R
authors.lastname: Campos-Cloute
authors.forename: Juan Jesús
authors.initials: JJ
authors.lastname: Ruiz
authors.forename: Antonia
authors.initials: A
authors.lastname: Serrano
authors.forename: Eduardo
authors.initials: E
authors.lastname: Blanco
authors.forename: Patricia
authors.initials: P
authors.lastname: Rivera
authors.forename: Juan
authors.initials: J
authors.lastname: Suárez
authors.forename: Miguel
authors.initials: M
authors.lastname: Romero-Cuevas
authors.forename: Mitona
authors.initials: M
authors.lastname: Pujadas
authors.forename: Esperanza
authors.initials: E
authors.lastname: Vergara-Moragues
authors.forename: Isolde
authors.initials: I
authors.lastname: Gornemann
authors.forename: Marta
authors.initials: M
authors.lastname: Torrens
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Torre
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodríguez de Fonseca
mesh_terms: D000328:Adult; D000553:Ambulatory Care; D000704:Analysis of Variance; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002853:Chromatography, Liquid / Q000379:methods; D019970:Cocaine-Related Disorders / Q000097:blood* / Q000453:epidemiology / Q000534:rehabilitation; D015897:Comorbidity; D017831:Diagnosis, Dual (Psychiatry); D063388:Endocannabinoids / Q000097:blood* / Q000737:chemistry; D004983:Ethanolamines / Q000097:blood* / Q000737:chemistry; D005229:Fatty Acids, Monounsaturated / Q000097:blood; D005260:Female; D005989:Glycerides / Q000097:blood* / Q000737:chemistry; D006801:Humans; D007406:Interview, Psychological; D016015:Logistic Models; D008297:Male; D001523:Mental Disorders / Q000097:blood* / Q000453:epidemiology; D010342:Patient Acceptance of Health Care; D012372:ROC Curve; D012720:Severity of Illness Index; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D015415:Biomarkers; D063388:Endocannabinoids; D004983:Ethanolamines; D005229:Fatty Acids, Monounsaturated; D005989:Glycerides; C022203:N-acylethanolamines
keywords: Abuse; DSM-IV-TR; cocaine; dependence; endocannabinoid; psychiatric co-morbidity