People with substance use disorder showed altered blood levels of endocannabinoid-related molecules, with distinct patterns when ADHD was also present.
Addiction researchers; psychiatrists treating dual-diagnosis patients; biomarker development scientists.
Machine learning identified endocannabinoid biomarkers with 72% accuracy
What the researchers found
SUD patients had lower plasma 2-AG and 2-LG and elevated acylethanolamides vs controls. ADHD comorbidity was associated with additional reductions in AEA, DGLEA, DHEA, and SEA, while PEA was elevated. Machine learning identified AEA, OEA, PEA, and SEA as key biomarkers with 72.1% accuracy.
Why it matters
Blood-based biomarkers for SUD and ADHD comorbidity could improve diagnosis and guide treatment.
The numbers in context
469 participants. Machine learning accuracy: 72.1%, ROC-AUC: 0.77. Key biomarkers: AEA, OEA, PEA, SEA.
How the study worked
Exploratory study of 469 participants: 136 controls, 267 SUD-only, 66 SUD+ADHD. Measured 12 endocannabinoid-related molecules via HPLC-MS/MS. Elastic Net regression for biomarker identification.
What this study cannot tell us
Cross-sectional design. Exploratory analysis needs independent validation. Plasma levels may not reflect brain ECS activity.
How to read the evidence
Exploratory cross-sectional study; biomarkers need validation in independent samples.
When this study was published
2025 study
The bigger picture
The endocannabinoid system is increasingly recognized as involved in both addiction and attention disorders. Blood-based biomarkers could help identify patients for ECS-targeted treatments.
Questions still open
- Can these biomarkers predict treatment response? Do the ECS alterations precede or follow substance use?
Common questions
What are endocannabinoid-related molecules?
Could this lead to a blood test for addiction or ADHD?
Read the original research
Exploratory study on plasma Acylglycerol and Acylethanolamide dysregulation in substance use and attention-deficit/hyperactivity disorder: Implications for novel biomarkers in dual diagnosis.
Progress in neuro-psychopharmacology & biological psychiatry, 138, 111350
Citation
Flores-López, María; Herrera-Imbroda, Jesús; Requena-Ocaña, Nerea; García-Marchena, Nuria; Araos, Pedro; Verheul-Campos, Julia; Ruiz, Juan Jesús; Pastor, Antoni; de la Torre, Rafael; Bordallo, Antonio; Pavón-Morón, Francisco Javier; Rodríguez de Fonseca, Fernando; Serrano, Antonia. (2025). Exploratory study on plasma Acylglycerol and Acylethanolamide dysregulation in substance use and attention-deficit/hyperactivity disorder: Implications for novel biomarkers in dual diagnosis.. Progress in neuro-psychopharmacology & biological psychiatry, 138, 111350. https://doi.org/10.1016/j.pnpbp.2025.111350
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