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Novel potential pharmacological approaches in treating eating disorders comorbid with substance use disorders - 20/07/25

Doi : 10.1016/j.biopha.2025.118327 
Zheng-Xiong Xi a, , Ewa Galaj b
a Addiction Biology Unit, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD 21224, USA 
b Department of Psychological and Brain Sciences, Colgate University, Hamilton, NY, USA 

Correspondence to: National Institute on Drug Abuse, Intramural Research Program, 251 Bayview Blvd, BRC, Baltimore, MD 21224, USA.National Institute on Drug Abuse, Intramural Research Program251 Bayview Blvd, BRCBaltimoreMD21224USA

Abstract

Eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED), frequently co-occur with substance use disorders (SUDs), affecting 20–30 % of individuals with either condition. This significant overlap is driven by shared neurobiological mechanisms, such as disruptions in dopamine, opioid, and cannabinoid systems, as well as by psychological traits including impulsivity, anxiety, and stress. While AN is often characterized by restrictive behaviors, BN and BED involve compulsive binge episodes, mirroring addiction patterns observed in SUDs. The current lack of FDA-approved treatments for co-occurring EDs and SUDs highlights the urgent need for innovative pharmacotherapies targeting overlapping neural pathways and behaviors. This article reviews the epidemiology and neurobiology of three major EDs, explores their behavior and metabolic commonalities, and examined recent advances in pharmacotherapy for EDs with comorbid SUDs. Promising treatments include olanzapine and ketamine, which improve compulsive behaviors and mood in AN and SUDs, as well as glucagon-like peptide 1 (GLP-1) receptor agonists, which reduce binge episodes and cravings in BED and SUDs. Hormonal agents such as leptin, ghrelin, and oxytocin are emerging as potential treatments due to their effects on appetite, reward systems, and stress regulation. Additionally, beta-caryophyllene and lisdexamfetamine demonstrate potential for binge-related disorders. Future research should prioritize large-scale clinical trials, integrated pharmacotherapeutic and psychological approaches, and a personalized medical treatment based on genetic and neurobiological profiles. This integrative strategy aims to address the intertwined challenges of EDs and SUDs, ultimately enhancing recovery and long-term health of affected individuals.

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Graphical Abstract




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Highlights

Anorexia nervosa (AN) and binge eating (BE) often co-occur with substance use disorders (SUDs).
This comorbidity arises from shared neural, genetic & behavioral mechanisms.
Olanzapine and ketamine improve compulsive behaviors and mood in AN and SUDs.
Oxytocin, leptin, and ghrelin also show potential for treating AN and SUD comorbidity.
GLP-1 receptor agonists, BCP, and LDX show promise in treating BE and SUDs.

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Abbreviations : ABA, ACC, ADHD, AN, AUD, BED, BCP, BMI, BN, BNST, CPP, CRF, DA, DEX, DR, ED, FAD, FDA, FR1, GOAT, GLP-1, GHS-R1a, HPA, IC, KO, LDX, LH, NAc, NTS, OXT, POMC, PFC, PPAR, SA, SUD, TLR-4, VTA, WFSBP, YFASS, Δ9-THC, 5-HT

Keywords : Eating disorders, binge eating, anorexia nervosa, comorbid substance use disorder, bulimia nervosa, GLP-1


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