Preprints.org · Oct 22, 2026

Reduction of Cocaine Craving and Sustained Abstinence During Tirzepatide Treatment in Two Patients with Obesity: A Case Report

By de Filippis LG, Bruno A

Cocaine use disorder (CUD) remains a major clinical challenge for which no pharmacological treatment has established efficacy. Experimental evidence suggests that incretin signalling may influence neural reward pathways involved in substance use, and preliminary clinical observations with glucagon-like peptide-1 (GLP-1) receptor agonists have suggested a possible reduction in cocaine craving. We describe a 40-year-old man and a 39-year-old woman with long-standing weekly intranasal cocaine use (approximately 3 g per episode, for 9 and 8 years, respectively) who received tirzepatide for obesity, starting at 2.5 mg once weekly for 4 weeks and titrated up to 10 mg weekly. Within the first month, both patients reported reduced cocaine craving and decreased frequency of use. Complete cessation occurred during the second month and was sustained for approximately six months, with a negative urine drug screen at follow-up. At 3 months, body weight had decreased by 11 kg and 9 kg, respectively. No adverse effects were reported. These cases describe a temporal association between tirzepatide treatment, reduced cocaine craving, decreased cocaine use, and sustained abstinence. Although causality cannot be inferred, the observations support further investigation of incretin-based therapies in CUD.

doi.org/10.20944/preprints202610.2170.v1Open accessInterventions