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首页> 外文期刊>Addiction biology >Differential response to IV carfentanil in chronic cocaine users and healthy controls
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Differential response to IV carfentanil in chronic cocaine users and healthy controls

机译：慢性可卡因使用者和健康对照者对IV卡芬太尼的差异反应

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Chronic cocaine exposure in both rodents and humans increases regional brain mu-opioid receptor (mOR) binding potential, suggesting that cocaine users might have an altered response to mOR agonists. We evaluated the response to IV carfentanil (a selective mOR agonist) in 23 cocaine users [mean (standard deviation) age 33.8 (4.0) years, 83% men] who underwent positron emission tomography (PET) scanning with [C-11]-carfentanil [44.7 (19.5) ng/kg] while housed on a closed research ward and 15 healthy non-drug-using controls [43.9 (14.2) years, 80% men] scanned [49.5 (12.6) ng/kg] as outpatients. Cocaine users had used for 8.7 (4.3) years and on 73 (22)% of days in the two weeks prior to PET scanning. Common adverse effects associated with mOR agonists (nausea, dizziness, headache, vomiting, itchiness) were assessed by self-report (five-point Likert scales) during and for 90 minutes after the scans. Cocaine users were significantly less likely than controls to report any symptom (30.4% versus 60%) and had fewer total symptoms [0.43 (0.73) versus 1.1 (1.0)] during scans, even after statistically controlling for age and carfentanil dose. These differences were also present after the scans and at repeat scans performed after about one week or 12 weeks of monitored cocaine abstinence. In a larger group of cocaine users and separate controls, there was no significant group difference in carfentanil half-life, suggesting that the observed difference was pharmacodynamically, rather than pharmacokinetically, based. These findings suggest that cocaine users are less responsive than healthy controls to mOR agonist adverse effects despite having increased regional brain mOR binding potential.
机译：啮齿动物和人类的长期可卡因暴露都增加了区域性脑类阿片受体（mOR）的结合潜力，这表明可卡因使用者可能对mOR激动剂的反应发生了改变。我们评估了使用[C-11]-进行正电子发射断层扫描（PET）扫描的23名可卡因使用者[平均（标准差）年龄33.8（4.0）岁，83％的男性）对卡芬太尼（选择性mOR激动剂）的反应。卡芬太尼[44.7（19.5）ng / kg]放在一个封闭的研究病房中，并有15名健康的非药物对照[43.9（14.2）岁，80％的男性]进行了门诊扫描[49.5（12.6）ng / kg]。可卡因使用者在PET扫描前的两周中已经使用8.7（4.3）年，每天使用73％（22）％。在扫描过程中和扫描后90分钟内，通过自我报告（五点李克特量表）评估与mOR激动剂相关的常见不良反应（恶心，头晕，头痛，呕吐，发痒）。即使在统计学控制年龄和卡芬太尼剂量后，可卡因使用者报告任何症状的可能性也大大低于对照组（30.4％对60％），并且在扫描过程中总症状较少（0.43（0.73）对1.1（1.0）]。这些差异也出现在扫描后以及监测可卡因戒断约一周或十二周后进行的重复扫描中。在较大数量的可卡因使用者和单独的对照组中，芬太尼的半衰期没有显着的组间差异，这表明观察到的差异是基于药效学而非药代动力学的。这些发现表明，可卡因使用者比健康对照者对mOR激动剂不良反应的反应要弱，尽管其区域脑mOR结合潜力增加了。

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