Department of Behavioral Science, University of Kentucky College of Medicine, 1100 Veterans Drive, Medical Behavioral Science Building, Lexington, KY, 40536-0086, USA.
Department of Behavioral Science, University of Kentucky College of Medicine, 1100 Veterans Drive, Medical Behavioral Science Building, Lexington, KY, 40536-0086, USA; Center on Drug and Alcohol Research, University of Kentucky College of Medicine, 845 Angliana Ave, Lexington, KY, 40508, USA.
Drug Alcohol Depend. 2021 Jan 1;218:108413. doi: 10.1016/j.drugalcdep.2020.108413. Epub 2020 Nov 23.
Cocaine use disorder is an unrelenting public health concern. Despite nearly four decades of research, an FDA approved medication is not yet available.
The objective of this human laboratory study was to demonstrate the initial efficacy, safety and tolerability of topiramate-phentermine combinations for cocaine use disorder.
Thirty-one (31) participants with cocaine use disorder completed this mixed-model inpatient laboratory study. Participants were maintained on topiramate (0 [N = 11], 50 [N = 9] or 100 [N = 11] mg/day). Each topiramate group was concurrently maintained on phentermine (0, 15, 30 mg). Drug self-administration, subjective responses and cardiovascular effects following acute doses of intranasal cocaine (0, 40, 80 mg) were determined during separate experimental sessions after at least seven (7) days of maintenance on each condition.
The three groups of participants were well matched demographically and generally did not differ significantly in their responses to a range of doses of intranasal cocaine (0, 10, 20, 40, 80 mg) during a medical safety session. Maintenance on topiramate and phentermine alone significantly decreased cocaine self-administration although these effects were modest in magnitude. Combining topiramate and phentermine robustly decreased cocaine self-administration. Topiramate and phentermine were well tolerated alone and combined, as well as in conjunction with cocaine.
The results of the present study support advancing topiramate-phentermine combinations as a putative pharmacotherapeutic for cocaine use disorder.
可卡因使用障碍是一个持续存在的公共卫生问题。尽管近四十年来进行了大量研究，但仍未获得美国食品药品监督管理局批准的药物。
本人体实验室研究的目的是证明托吡酯-苯丁胺联合治疗可卡因使用障碍的初步疗效、安全性和耐受性。
31 名可卡因使用障碍患者完成了这项混合模型住院实验室研究。参与者接受托吡酯（0 [N = 11]、50 [N = 9]或 100 [N = 11] mg/天）治疗。每个托吡酯组同时接受苯丁胺（0、15、30 mg）治疗。在至少 7 天的每种条件维持治疗后，通过单独的实验会议，确定急性鼻内可卡因（0、40、80 mg）给药后药物自我给药、主观反应和心血管效应。
三组参与者在人口统计学上匹配良好，并且在医疗安全会议期间，他们对一系列鼻内可卡因剂量（0、10、20、40、80 mg）的反应通常没有显著差异。单独使用托吡酯和苯丁胺维持治疗可显著减少可卡因自我给药，尽管这些效果的幅度较小。联合使用托吡酯和苯丁胺可显著减少可卡因自我给药。托吡酯和苯丁胺单独使用或联合使用，以及与可卡因联合使用时均具有良好的耐受性。
本研究的结果支持将托吡酯-苯丁胺联合治疗作为可卡因使用障碍的潜在药物治疗方法。
