Gustavo A Angarita1, David Matuskey2, Brian Pittman3, Jessica L Costeines4, Marc N Potenza5, Ania M Jastreboff6, Heath D Schmidt7, Robert T Malison4. 1. Department of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven, CT, 06511, USA; Clinical Neuroscience Research Unit, Connecticut Mental Health Center, 34 Park Street, New Haven, CT, 06519, USA. Electronic address: gustavo.angarita@yale.edu. 2. Department of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven, CT, 06511, USA; Department of Radiology and Biomedical Imaging, Yale University School of Medicine, 801 Howard Ave, New Haven, CT, 06519, USA; Department of Neurology, Yale University School of Medicine, 15 York Street, New Haven, CT, 06510, USA. 3. Department of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven, CT, 06511, USA. 4. Department of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven, CT, 06511, USA; Clinical Neuroscience Research Unit, Connecticut Mental Health Center, 34 Park Street, New Haven, CT, 06519, USA. 5. Department of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven, CT, 06511, USA; Child Study Center, Yale University School of Medicine, New Haven, CT, 06510, USA; Department of Neuroscience, Yale University, New Haven, CT, 06510, USA; Connecticut Mental Health Center, New Haven, CT, 06519, USA; Connecticut Council on Problem Gambling, Wethersfield, CT, 06109, USA. 6. Department of Internal Medicine (Endocrinology & Metabolism), Yale University School of Medicine, New Haven, CT, 06519, USA; Department of Pediatrics (Pediatric Endocrinology), Yale University School of Medicine, New Haven, CT, 06520, USA. 7. Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, 125 South 31stStreet, Philadelphia, PA, 19104, USA; Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, 125 South 31stStreet, Rm 2214, Philadelphia, PA, 19104, USA.
Abstract
BACKGROUND: Preclinical rodent studies have demonstrated reduced cocaine taking after administration of glucagon-like peptide 1 (GLP-1) analogues. We investigated effects of a GLP-1 analogue (exenatide) on behavioral and subjective effects of cocaine in individuals with cocaine use disorder (CUD). METHODS: Non-treatment-seeking CUD subjects underwent two human laboratory cocaine self-administration test sessions following an acute 3 -h pre-treatment with exenatide (5 mcg; subcutaneously) or placebo. Primary outcomes consisted of infusions of cocaine and visual analog scale self-ratings of euphoria and wanting cocaine. Secondary outcomes consisted of pertinent hormone levels (GLP-1, insulin, and amylin). RESULTS: Thirteen individuals completed the study. Acute pretreatment with exenatide versus placebo did not change cocaine infusions (8.5 ± 1.2 vs. 9.1 ± 1.2; p = 0.39), self-reported euphoria (4.4 ± 0.8 vs. 4.1 ± 0.8; p = 0.21), or wanting of cocaine (5.6 ± 0.9 vs. 5.4 ± 0.9; p = 0.46). Exenatide vs. placebo reduced levels of GLP-1 (p = 0.03) and insulin (p = 0.02). Self-administered cocaine also reduced levels of GLP-1 (p < 0.0001), insulin (p < 0.0001), and amylin (p < 0.0001). CONCLUSIONS: We did not find evidence that low dose exenatide alters cocaine self-administration or the subjective effects of cocaine in people with CUD. Limitations such as single acute rather than chronic pre-treatment, as well as evaluation of only one dose, preclude drawing firm conclusions about the efficacy of exenatide. Exenatide and cocaine independently reduced levels of GLP-1 and insulin, while cocaine also reduced levels of amylin.
BACKGROUND: Preclinical rodent studies have demonstrated reduced cocaine taking after administration of glucagon-like peptide 1 (GLP-1) analogues. We investigated effects of a GLP-1 analogue (exenatide) on behavioral and subjective effects of cocaine in individuals with cocaine use disorder (CUD). METHODS: Non-treatment-seeking CUD subjects underwent two human laboratory cocaine self-administration test sessions following an acute 3 -h pre-treatment with exenatide (5 mcg; subcutaneously) or placebo. Primary outcomes consisted of infusions of cocaine and visual analog scale self-ratings of euphoria and wanting cocaine. Secondary outcomes consisted of pertinent hormone levels (GLP-1, insulin, and amylin). RESULTS: Thirteen individuals completed the study. Acute pretreatment with exenatide versus placebo did not change cocaine infusions (8.5 ± 1.2 vs. 9.1 ± 1.2; p = 0.39), self-reported euphoria (4.4 ± 0.8 vs. 4.1 ± 0.8; p = 0.21), or wanting of cocaine (5.6 ± 0.9 vs. 5.4 ± 0.9; p = 0.46). Exenatide vs. placebo reduced levels of GLP-1 (p = 0.03) and insulin (p = 0.02). Self-administered cocaine also reduced levels of GLP-1 (p < 0.0001), insulin (p < 0.0001), and amylin (p < 0.0001). CONCLUSIONS: We did not find evidence that low dose exenatide alters cocaine self-administration or the subjective effects of cocaine in people with CUD. Limitations such as single acute rather than chronic pre-treatment, as well as evaluation of only one dose, preclude drawing firm conclusions about the efficacy of exenatide. Exenatide and cocaine independently reduced levels of GLP-1 and insulin, while cocaine also reduced levels of amylin.
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