Anna R Reynolds1, Justin C Strickland2, William W Stoops3, Joshua A Lile3, Craig R Rush4. 1. Department of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, 789 South Limestone, Lexington, KY 40536-0596, USA. 2. Department of Psychology, University of Kentucky Arts and Sciences, 110 Kastle Hall Lexington, KY 40506-0044, USA. 3. Department of Behavioral Science, University of Kentucky College of Medicine, 133 Medical Behavioral Science Building, Lexington, KY 40536-0086, USA; Department of Psychology, University of Kentucky Arts and Sciences, 110 Kastle Hall Lexington, KY 40506-0044, USA; Department of Psychiatry, University of Kentucky College of Medicine, 245 Fountain Court, Lexington, KY 40509, USA. 4. Department of Behavioral Science, University of Kentucky College of Medicine, 133 Medical Behavioral Science Building, Lexington, KY 40536-0086, USA; Department of Psychology, University of Kentucky Arts and Sciences, 110 Kastle Hall Lexington, KY 40506-0044, USA; Department of Psychiatry, University of Kentucky College of Medicine, 245 Fountain Court, Lexington, KY 40509, USA. Electronic address: crush2@email.uky.edu.
Abstract
BACKGROUND: Medications development efforts for methamphetamine-use disorder have targeted central monoamines because these systems are directly involved in the effects of methamphetamine. Buspirone is a dopamine autoreceptor and D3 receptor antagonist and partial agonist at serotonin 1A receptors, making it a logical candidate medication for methamphetamine-use disorder. Buspirone effects on abuse-related behaviors of methamphetamine have been mixed in clinical and preclinical studies. Experimental research using maintenance dosing, which models therapeutic use, is limited. This study evaluated the influence of buspirone maintenance on the reinforcing effects of methamphetamine using a self-administration procedure, which has predictive validity for clinical efficacy. The impact of buspirone maintenance on the subjective and cardiovascular response to methamphetamine was also determined. METHODS:Eight research participants (1 female) reporting recent illicit stimulant use completed aplacebo-controlled, crossover, double-blind protocol in which the pharmacodynamic effects of intranasal methamphetamine (0, 15, and 30mg) were assessed after at least 6days of buspirone (0 and 45mg/day) maintenance. RESULTS:Intranasal methamphetamine functioned as a reinforcer and produced prototypical stimulant-like subjective (e.g., increased ratings of Good Effects and Like Drug) and cardiovascular (e.g., elevated blood pressure) effects. These effects of methamphetamine were similar under buspirone and placebo maintenance conditions. Maintenance on buspirone was well tolerated and devoid of effects when administered alone. CONCLUSIONS: These data suggest that buspirone is unlikely to be an effective pharmacotherapy for methamphetamine-use disorder. Given the central role of monoamines in methamphetamine-use disorder, it is reasonable for future studies to continue to target these systems.
RCT Entities:
BACKGROUND: Medications development efforts for methamphetamine-use disorder have targeted central monoamines because these systems are directly involved in the effects of methamphetamine. Buspirone is a dopamine autoreceptor and D3 receptor antagonist and partial agonist at serotonin 1A receptors, making it a logical candidate medication for methamphetamine-use disorder. Buspirone effects on abuse-related behaviors of methamphetamine have been mixed in clinical and preclinical studies. Experimental research using maintenance dosing, which models therapeutic use, is limited. This study evaluated the influence of buspirone maintenance on the reinforcing effects of methamphetamine using a self-administration procedure, which has predictive validity for clinical efficacy. The impact of buspirone maintenance on the subjective and cardiovascular response to methamphetamine was also determined. METHODS: Eight research participants (1 female) reporting recent illicit stimulant use completed a placebo-controlled, crossover, double-blind protocol in which the pharmacodynamic effects of intranasal methamphetamine (0, 15, and 30mg) were assessed after at least 6days of buspirone (0 and 45mg/day) maintenance. RESULTS: Intranasal methamphetamine functioned as a reinforcer and produced prototypical stimulant-like subjective (e.g., increased ratings of Good Effects and Like Drug) and cardiovascular (e.g., elevated blood pressure) effects. These effects of methamphetamine were similar under buspirone and placebo maintenance conditions. Maintenance on buspirone was well tolerated and devoid of effects when administered alone. CONCLUSIONS: These data suggest that buspirone is unlikely to be an effective pharmacotherapy for methamphetamine-use disorder. Given the central role of monoamines in methamphetamine-use disorder, it is reasonable for future studies to continue to target these systems.
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