Department of Psychiatry, Division on Substance Abuse, New York State Psychiatric Institute, and College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Neuropsychopharmacology. 2013 Nov;38(12):2427-38. doi: 10.1038/npp.2013.143. Epub 2013 Jun 5.
Despite the prevalent worldwide abuse of stimulants, such as amphetamines and cocaine, no medications are currently approved for treating this serious public health problem. Both preclinical and clinical studies suggest that the opioid antagonist naltrexone (NTX) is effective in reducing the abuse liability of amphetamine, raising the question of whether similar positive findings would be obtained for cocaine. The purpose of this study was to evaluate the ability of oral NTX to alter the cardiovascular and subjective effects of D-amphetamine (D-AMPH) and cocaine (COC). Non-treatment-seeking COC users (N=12) completed this 3-week inpatient, randomized, crossover study. Participants received 0, 12.5, or 50 mg oral NTX 60 min before active or placebo stimulant administration during 10 separate laboratory sessions. Oral AMPH (0, 10, and 20 mg; or all placebo) was administered in ascending order within a laboratory session using a 60-min interdose interval. Smoked COC (0, 12.5, 25, and 50 mg; or all placebo) was administered in ascending order within a laboratory session using a 14-min interdose interval. Active COC and AMPH produced dose-related increases in cardiovascular function that were of comparable magnitude. In contrast, COC, but not AMPH, produced dose-related increases in several subjective measures of positive drug effect (eg, high, liking, and willingness to pay for the drug). NTX did not alter the cardiovascular effects of AMPH or COC. NTX also did not alter positive subjective ratings after COC administration, but it did significantly reduce ratings of craving for COC and tobacco during COC sessions. These results show that (1) oral AMPH produces minimal abuse-related subjective responses in COC smokers, and (2) NTX reduces craving for COC and tobacco during COC sessions. Future studies should continue to evaluate NTX as a potential anti-craving medication for COC dependence.
尽管安非他命和可卡因等兴奋剂在全球范围内普遍滥用，但目前尚无药物被批准用于治疗这一严重的公共卫生问题。临床前和临床研究表明，阿片受体拮抗剂纳曲酮（NTX）可有效降低安非他命的滥用倾向，这引发了一个问题，即类似的积极发现是否也适用于可卡因。本研究旨在评估口服纳曲酮改变 D-苯丙胺（D-AMPH）和可卡因（COC）心血管和主观效应的能力。12 名非治疗性可卡因使用者完成了这项为期 3 周的住院、随机、交叉研究。参与者在 10 个单独的实验室会议中，在活性或安慰剂兴奋剂给药前 60 分钟，接受 0、12.5 或 50mg 口服纳曲酮。在一个实验室会议中，口服 AMPH（0、10 和 20mg；或均为安慰剂）以 60 分钟的间隔递增给药。在一个实验室会议中，以 14 分钟的间隔递增给药，口服 COC（0、12.5、25 和 50mg；或均为安慰剂）。活性 COC 和 AMPH 产生了剂量相关的心血管功能增加，其幅度相当。相比之下，COC 而不是 AMPH 产生了剂量相关的几种正面药物效应的主观测量增加（例如，高、喜欢和愿意为药物支付的意愿）。NTX 没有改变 AMPH 或 COC 的心血管作用。NTX 也没有改变 COC 给药后的正面主观评分，但它确实显著降低了 COC 期间对 COC 和烟草的渴望评分。这些结果表明：（1）口服 AMPH 在 COC 吸烟者中产生最小的与滥用相关的主观反应；（2）NTX 降低了 COC 期间对 COC 和烟草的渴望。未来的研究应继续评估 NTX 作为 COC 依赖的潜在抗渴望药物。
