Evaluation of plasma-free endocannabinoids and their congeners in abstinent cocaine addicts seeking outpatient treatment: Impact of psychiatric co-morbidity

Francisco Javier Pavõn, Pedro Araos, Antoni Pastor, Montserrat Calado, María Pedraz, Rafael Campos-Cloute, Juan Jesús Ruiz, Antonia Serrano, Eduardo Blanco, Patricia Rivera, Juan Suárez, Miguel Romero-Cuevas, Mitona Pujadas, Esperanza Vergara-Moragues, Isolde Gornemann, Marta Torrens, Rafael De La Torre, Fernando Rodríguez De Fonseca

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34 Citations (Scopus)


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. © 2013 Society for the Study of Addiction.
Original languageEnglish
Pages (from-to)955-969
JournalAddiction Biology
Issue number6
Publication statusPublished - 1 Nov 2013


  • Abuse
  • cocaine
  • dependence
  • endocannabinoid
  • psychiatric co-morbidity


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