Differential response to IV carfentanil in chronic cocaine users and healthy controls.
Differential response to IV carfentanil in chronic cocaine users and healthy controls.
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DOI：
10.1111/j.1369-1600.2010.00256.x
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发表时间：
2012-01
影响因子：
3.4
通讯作者：
Gorelick DA
中科院分区：
文献类型：
--
作者：
Minkowski CP;Epstein D;Frost JJ;Gorelick DA
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 [SD] age 33.8 [4.0] years, 83% men) who underwent 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 (5-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% vs. 60%) and had fewer total symptoms (0.43 [0.73] vs. 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 done 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.
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