Semaglutide for Craving Reduction in a Cocaine Dependent Patient: A Case Report

Alessandro Matteo Sileoni; Elena Teresa Turco; Francesco Semeraro; Clara Cavallotto; Alessio Mosca; Stefania Chiappini; Giovanni Martinotti

doi:10.53941/cna.2025.100003

Abstract

Semaglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist approved for type 2 diabetes and obesity, has demonstrated the ability to reduce drug-seeking behaviors in animal models. We report the case of a 33-year-old woman with severe Cocaine Use Disorder (CUD) and comorbid borderline personality disorder, who also presented with recurrent binge-eating episodes. While continuing the psychopharmacological interventions, an off-label oral semaglutide was initiated (starting and maintaining dose 3 mg daily). Baseline assessments included the Cocaine Craving Questionnaire (CCQ), Barratt Impulsiveness Scale (BIS-11), Eating Disorder Inventory (EDI), Hamilton Depression Rating Scale (HDRS), and Hamilton Anxiety Rating Scale (HARS). At one and three months, repeat evaluations revealed a pronounced decline in cocaine craving, with CCQ subscale scores (Reward, Relief, Obsessive) falling by more than 75%. Impulsivity measured by BIS-11 decreased from 80 at baseline to 33 at three months. Binge-eating behaviors remitted completely, as evidenced by normalization of EDI scores. Depressive symptoms improved modestly (HDRS from 9 to 7), and anxiety symptoms decreased substantially (HARS from 11 to 4). The patient tolerated semaglutide well, reporting no adverse effects. This single-case observation suggests that GLP-1 receptor agonism as add-on to a psychopharmacological treatment may alleviate core features of substance use disorders—craving, impulsivity, and associated affective dysregulation—while also addressing metabolic comorbidities. Potential mechanisms include modulation of mesolimbic dopamine pathways and enhancement of satiety signals, which together may reduce the reinforcing properties of cocaine.

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