Exploratory study on plasma Acylglycerol and Acylethanolamide dysregulation in substance use and attention-deficit/hyperactivity disorder: Implications for novel biomarkers in dual diagnosis

Flores López, María; Herrera-Imbroda, Jesús; Requena-Ocaña, Nerea; García-Marchena, Nuria; Araos, Pedro; Verheul-Campos, Julia; Ruiz, Juan Jesús; Pastor, Antonio; Torre Fornell, Rafael de la; Bordallo, Antonio; Pavón-Morón, Francisco Javier; Rodríguez de Fonseca, Fernando; Serrano, Antonia

Exploratory study on plasma Acylglycerol and Acylethanolamide dysregulation in substance use and attention-deficit/hyperactivity disorder: Implications for novel biomarkers in dual diagnosis

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dc.contributor.author Flores López, María
dc.contributor.author Herrera-Imbroda, Jesús
dc.contributor.author Requena-Ocaña, Nerea
dc.contributor.author García-Marchena, Nuria
dc.contributor.author Araos, Pedro
dc.contributor.author Verheul-Campos, Julia
dc.contributor.author Ruiz, Juan Jesús
dc.contributor.author Pastor, Antonio
dc.contributor.author Torre Fornell, Rafael de la
dc.contributor.author Bordallo, Antonio
dc.contributor.author Pavón-Morón, Francisco Javier
dc.contributor.author Rodríguez de Fonseca, Fernando
dc.contributor.author Serrano, Antonia
dc.date.accessioned 2025-05-12T06:50:54Z
dc.date.available 2025-05-12T06:50:54Z
dc.date.issued 2025
dc.description.abstract Substance use disorder (SUD) is a major global public health challenge, frequently co-occurring with psychiatric conditions such as attention-deficit/hyperactivity disorder (ADHD). Endocannabinoid system (ECS) dysregulation has been implicated in both SUD and ADHD, but the interplay between these conditions remains poorly understood. This study investigates plasma concentrations of endocannabinoid-congeners in individuals with SUD, with and without comorbid ADHD, to identify potential biomarkers. This exploratory study included 469 participants divided into three groups: (1) healthy controls (n = 136), (2) patients with SUD without ADHD (n = 267), and (3) patients with SUD and comorbid ADHD (n = 66). Plasma concentrations of 12 endocannabinoid-related molecules, including acylglycerols (2-AG, 2-LG, 2-OG) and acylethanolamides (AEA, DEA, DHEA, DGLEA, LEA, OEA, PEA, POEA, and SEA), were quantified using high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). A multinomial Elastic Net regression model was applied to assess their biomarker potential. Patients with SUD exhibited significantly lower plasma concentrations of 2-AG and 2-LG compared to controls, while most acylethanolamides were elevated, except for POEA and SEA. ADHD comorbidity was associated with lower concentrations of 2-AG, 2-LG, AEA, DGLEA, DHEA, and SEA, while PEA was elevated. Machine learning analysis identified AEA, OEA, PEA, and SEA as key biomarkers, achieving an accuracy of 72.1 % and an ROC-AUC of 0.77. This study suggests distinct ECS alterations in SUD and comorbid ADHD, highlighting endocannabinoid-congeners as potential biomarkers. Future research should validate these findings in larger cohorts and explore ECS-targeted therapeutic interventions for dual-diagnosis populations.
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dc.identifier.citation Flores-López M, Herrera-Imbroda J, Requena-Ocaña N, García-Marchena N, Araos P, Verheul-Campos J, et al. Exploratory study on plasma Acylglycerol and Acylethanolamide dysregulation in substance use and attention-deficit/hyperactivity disorder: Implications for novel biomarkers in dual diagnosis. Prog Neuropsychopharmacol Biol Psychiatry. 2025 Apr 2;138:111350. DOI: 10.1016/j.pnpbp.2025.111350
dc.identifier.doi http://dx.doi.org/10.1016/j.pnpbp.2025.111350
dc.identifier.issn 0278-5846
dc.identifier.uri http://hdl.handle.net/10230/70347
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Prog Neuropsychopharmacol Biol Psychiatry. 2025 Apr 2;138:111350
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword Acylethanolamide
dc.subject.keyword Acylglycerol
dc.subject.keyword Alcohol
dc.subject.keyword Attention-deficit/hyperactivity disorder
dc.subject.keyword Biomarker
dc.subject.keyword Cocaine
dc.subject.keyword Endocannabinoid
dc.subject.keyword Machine learning
dc.title Exploratory study on plasma Acylglycerol and Acylethanolamide dysregulation in substance use and attention-deficit/hyperactivity disorder: Implications for novel biomarkers in dual diagnosis
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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