Psychological/Methodological Issues In Substance Abuse

在临床试验的范围内，该科评估与研究和治疗有关的方法学问题，如监测药物使用情况。在之前发表的一项研究中，我们发现，在活跃的街头吸毒者中，可卡因的半衰期比偶尔吸食者的半衰期更长，尽管其主要代谢物苯甲酰ecGonine的半衰期没有改变，这表明经常使用可卡因会改变其处置和消除(Moolchan et，Cone EJ，Wtsadik A，Hustis MA，Preston KL)。J分析毒理学，24,458-466,2000)。在之前发表的另一项研究中，我们表明汗斑可以作为监测药物使用的替代方法，其优势是每周一次的检测窗口(Huestis MA，Preston KL，Wong CJ，Umbricht A，Cone EJ，)。《分析毒理学》，24,509-521,2000)。在第三项研究中，我们评估了一种新的尿液6-乙酰吗啡(6-AM)检测方法的性能，6-乙酰吗啡是一种海洛因代谢物，是海洛因使用的特异性标志。6-AM检测在临床上很重要，因为摄入罂粟籽或合法的阿片类镇痛剂可以在尿液阿片类药物测试中产生阳性结果，这些测试只筛查海洛因的非特异性代谢物，如吗啡和可待因。在联邦授权的工作场所药物测试计划中，现在需要进行6-AM GC-MS分析。同样，卫生与公众服务部(HHS)要求吗啡阳性标本在截止浓度为*10纳克/毫升的情况下，用GC/MS重新测试6-AM。(在这两套指南中，吗啡和可待因的筛查截止浓度已从*300毫微克/毫升提高到*2000毫克/毫升。)筛选6-AM的一个缺点是它的半衰期只有0.6小时，这使得在接触海洛因后几个小时内就能在尿液中检测到它。我们每周三次收集参加美沙酮维持计划的44名参与者的尿样，以评估新的检测方法及其在新的截止浓度下的表现。筛查的1377份尿样中，阿片类药物*300 ng/mL阳性261例，占18.9%，阿片类药物*2000 ng/mL阳性153例，占11.1%，上午6时阳性55例，占4.0%。在253份可用于GC/MS分析的样本中，231份或91.3%的样本确认吗啡或可待因的含量为*300 ng/mL。在可供GC/MS分析的151×2000 ng/mL中，122个或80.8%的吗啡或可待因被确认为*2000 ng/mL。所有6-AM阳性标本经GC/MS检测均为阳性，检出浓度为10 ng/mL。此外，筛选*300但低于2000 ng/毫升的阿片类药物的样本中，没有一例确认*10 ng/毫升的6-AM呈阳性。在55个早上6点呈阳性的尿样中，有44个(80%)的尿液浓度在201至9096毫微克/毫升之间，这表明最近使用了海洛因。将联邦工作场所药物测试方案的阿片类药物筛选和确认截止日期从300 ng/毫升增加到2000 ng/毫升，导致参加美沙酮维持治疗计划的个人的阿片类药物阳性测试减少了8%。然而，最近的海洛因使用，按照尿液6-AM*10 ng/毫升浓度的定义，不受这一变化的影响。虽然6-AM筛选试验发现的阿片类药物阳性试验要少得多，只有4%，而鸦片类药物*2000 ng/mL试验的阳性试验只有11%，但与可能使用罂粟籽或可待因相比，它清楚地识别了海洛因。此外，尽管6-AM与总吗啡浓度有显著相关性，但不能从GC/MS 6-AM浓度可靠地预测尿总吗啡浓度。用针对6-AM的阿片类药物筛选试验取代用于测量总吗啡的阿片类药物筛选试验将导致较少的阿片类药物阳性试验的检测。6-AM检测可能有助于检测最近的海洛因暴露，并在治疗和员工援助计划中减少连续尿检中潜在的“结转”阳性。在一项即将完成的大型研究中，我们正在比较美沙酮治疗药物监测在各种生物基质上的效用，包括血浆、唾液和汗液；我们还计划检测皮质醇和催乳素水平，作为美沙酮药效的可能标记物。

Within the context of clinical trials, the section evaluates methodological issues relevant to both research and treatment, such as monitoring drug use. In a previously published study, we found that cocaine's half-life is longer in active street users than in occasional users despite there being no change in the half-life of its main metabolite benzoylecgonine, suggesting that regular use of cocaine alters its the disposition and elimination (Moolchan ET, Cone EJ, Wtsadik A, Huestis MA, Preston KL. J Analytical Toxicology, 24, 458-466, 2000). In another previously published study, we showed that sweat patches could be an alternate method for monitoring drug use, with the advantage of a week-ly window of detection (Huestis MA, Preston KL, Wong CJ, Umbricht A, Cone EJ,. J Analytical Toxicology, 24, 509-521, 2000). In a third study, we assessed the performance of a new urine assay for 6-acetylmorphine (6-AM), a heroin metabolite that is a specific marker for heroin use. 6-AM detection is clinically important because the ingestion of poppy seeds or licit opiate analgesics can produce positive results on urine opiate tests that screen only for heroin-nonspecific metabolites such as morphine and codeine. In the federally mandated workplace drug-testing program, 6-AM GC-MS analysis is now required. Similarly, the Department of Health and Human Services (HHS) requires morphine-positive specimens to be retested by GC/MS for 6-AM at a cutoff concentration of * 10 ng/mL. (In both sets of guidelines, the screening cutoff for morphine and codeine has been raised from * 300 ng/mL to * 2000 ng/mL.) One drawback of screening for 6-AM is its half-life of only 0.6 hours, which makes it detectable in urine for only a few hours after heroin exposure. We collected urine specimens three times per week from 44 participants in a methadone-maintenance program in order to assess the new assay and its performance at the new cutoff concentrations. Of the 1377 urine specimens screened, 261 or 18.9% were positive for opiates at * 300 ng/mL, 153 or 11.1% were positive for opiates at * 2000 ng/mL, and 55 or 4.0% were positive for 6AM at * 10 ng/mL. Of the 253 specimens * 300 ng/mL and available for GC/MS analysis, 231 or 91.3% were confirmed for morphine or codeine at * 300 ng/mL. Of the 151 * 2000 ng/mL and available for GC/MS analysis, 122 or 80.8% were confirmed for morphine or codeine at * 2000 ng/mL. All specimens screening positive for 6-AM also confirmed positive by GC/MS at * 10 ng/mL. Furthermore, none of the specimens screening at * 300 but less than 2000 ng/mL for opiates confirmed positive for 6-AM at * 10 ng/mL. Forty-four (80%) of the 55 positive 6AM urine specimens had concentrations between 201 and 9096 ng/mL, suggesting recent heroin use. Increasing the opiate screening and confirmation cutoffs for the federal workplace drug-testing program from 300 to 2000 ng/mL, resulted in 8% fewer opiate positive tests in individuals participating in a methadone maintenance treatment program. However, recent heroin use, as defined by a urine concentration of 6-AM * 10 ng/mL, was not affected by this change. Although the 6-AM screening assay identified far fewer positive opiate tests, 4% as compared to 11% in the opiate * 2000 ng/mL assay, it clearly identified heroin, as compared to possible poppy seed or codeine use. In addition, although there was a significant correlation between 6-AM and total morphine concentrations, total urinary morphine could not be reliably predicted from the GC/MS 6-AM concentrations. Replacement of an opiate screening assay directed at the measurement of total morphine with an assay directed toward 6-AM would result in the detection of fewer opiate positive tests. The 6-AM assay could be useful in detection of recent heroin exposure and in reducing potential "carryover" positives in consecutive urine tests in treatment and employee assistance programs. In a large study now nearing completion, we are comparing the utility of therapeutic drug monitoring for methadone across a variety of biological matrices, including plasma, saliva, and sweat; we are also planning to assay levels of cortisol and prolactin as possible markers of methadone's pharmacodynamic efficacy.