Incubation of Cue-Induced Craving in Adults Addicted to Cocaine Measured by Electroencephalography.
Incubation of Cue-Induced Craving in Adults Addicted to Cocaine Measured by Electroencephalography.
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DOI：
10.1001/jamapsychiatry.2016.2181
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发表时间：
2016-11-01
期刊：
影响因子：
25.8
通讯作者：
Goldstein, Rita Z.
中科院分区：
文献类型：
--
作者：
Parvaz, Muhammad A.;Moeller, Scott J.;Goldstein, Rita Z.
毒瘾复发的一个常见诱因是通过接触到以前与吸毒有关的线索而产生的渴望。临床前研究一致表明，在戒断的初始阶段，有线索诱导的药物寻找潜伏期，随后随着时间的推移而下降。在人类中，酒精、尼古丁和甲基苯丙胺成瘾已显示出潜伏期效应，但对海洛因或可卡因成瘾则没有。了解人类在戒断期间线索诱导的渴望的轨迹对成瘾药物具有重要意义。利用线索诱导反应的主观和客观指标来评估人类对可卡因的线索诱导渴望。从2007年6月19日至2012年11月26日，76名可卡因成瘾者参加了这项以实验室为基础的横断面研究，他们的戒断时间不同（2天、1周、1个月、6个月和1年）。脑电图的晚期正电位成分是一种公认的激励显著性标记，用于跟踪这些自我选择组对药物线索的动机性注意。参与者还在看到线索之前完成了对可卡因渴望的主观评分，在看到与可卡因有关的图片之后完成了对可卡因“喜欢”（对可卡因的享乐感觉）和“想要”（对可卡因的渴望）的评分。数据分析时间为2015年6月5日至2016年3月30日。在对可卡因相关图片的反应中，后期正电位振幅和喜欢和想要可卡因的等级被量化并在组间进行比较。76例可卡因成瘾者中，戒断2天19例（25%），1周20例（26%），1个月15例（20%），6个月12例（16%），1年10例（13%）。在药物提示下，平均（SD）晚期阳性电位振幅呈抛物线轨迹，在戒断1个月（1.26[1.36]µV）和6个月（1.17[1.19]µV）时较高，在戒断2天（0.17[1.09]µV）、1周（0.36[1.26]µV）和1年（- 0.27[1.74]µV）时较低（P = 0.02，偏η2 = 0.16）。相比之下，基线渴望（平均[SD]评分：2天，26.05[9.85]，1周，18.70[11.01]，1个月，10.87[10.70]，6个月，6.92[8.47]，1年，3.00[3.77]）和线索诱导喜欢（平均[SD]评分：2天，3.06[2.34]，1周，2.33[2.87]，1个月，1.15[2.03]，6个月，1.00[2.24]，1年，1.00[1.26]）和渴望(平均[SD]评分：2天，3.44[2.62]，1周，2.72[2.87]，1个月，1.46[2.33]，6个月，1.00[2.33]，6个月，1.00 [2.16]；1年，1.00[1.55])的可卡因戒断2天至1年呈线性下降（P≤0.001，偏η2 bb0 0.26）。对药物线索的晚期阳性潜在反应，表明了动机性注意，显示了与动物模型相似的轨迹。相比之下，我们没有发现主观线索诱导的渴望的潜伏期。因此，与主观报告相比，客观脑电图测量可能是线索诱导复发的脆弱性的更好指标，尽管这一假设必须经过经验检验。这些结果表明，在戒断1 - 6个月期间进行干预是很重要的，因为在这段时间，成瘾者可能最容易、也最不容易意识到复发的风险。
A common trigger for relapse in drug addiction is the experience of craving via exposure to cues previously associated with drug use. Preclinical studies have consistently demonstrated incubation of cue-induced drug-seeking during the initial phase of abstinence, followed by a decline over time. In humans, the incubation effect has been shown for alcohol, nicotine, and methamphetamine addictions, but not for heroin or cocaine addiction. Understanding the trajectory of cue-induced craving during abstinence in humans is of importance for addiction medicine. To assess cue-induced craving for cocaine in humans using both subjective and objective indices of cue-elicited responses. Seventy-six individuals addicted to cocaine with varying durations of abstinence (ie, 2 days, 1 week, 1 month, 6 months, and 1 year) participated in this laboratory-based cross-sectional study from June 19, 2007, to November 26, 2012. The late positive potential component of electroencephalography, a recognized marker of incentive salience, was used to track motivated attention to drug cues across these self-selected groups. Participants also completed subjective ratings of craving for cocaine before presentation of a cue, and ratings of cocaine “liking” (hedonic feelings toward cocaine) and “wanting” (craving for cocaine) after presentation of cocaine-related pictures. Data analysis was conducted from June 5, 2015, to March 30, 2016. The late positive potential amplitudes and ratings of liking and wanting cocaine in response to cocaine-related pictures were quantified and compared across groups. Among the 76 individuals addicted to cocaine, 19 (25%) were abstinent for 2 days, 20 (26%) were abstinent for 1week, 15 (20%) were abstinent for 1 month, 12 (16%) were abstinent for 6 months, and 10 (13%) were abstinent for 1 year. In response to drug cues, the mean (SD) late positive potential amplitudes showed a parabolic trajectory that was higher at 1 (1.26 [1.36] µV) and 6 (1.17 [1.19] µV) months of abstinence and lower at 2 days (0.17 [1.09] µV), 1week (0.36 [1.26] µV), and 1 year (−0.27 [1.74] µV) of abstinence (P = .02, partial η2 = 0.16). In contrast, the subjective assessment of baseline craving (mean [SD] rating: 2 days, 26.05 [9.85]; 1week, 18.70 [11.01]; 1 month, 10.87 [10.70]; 6 months, 6.92 [8.47]; and 1 year, 3.00 [3.77]) and cue-induced liking (mean [SD] rating: 2 days, 3.06 [2.34]; 1week, 2.33 [2.87]; 1 month, 1.15 [2.03]; 6 months, 1.00 [2.24]; and 1 year, 1.00 [1.26]) and wanting (mean [SD] rating: 2 days, 3.44 [2.62]; 1week, 2.72 [2.87]; 1 month, 1.46 [2.33]; 6 months, 1.00 [2.16]; and 1 year, 1.00 [1.55]) of cocaine showed a linear decline from 2 days to 1 year of abstinence (P ≤ .001, partial η2 > 0.26). The late positive potential responses to drug cues, indicative of motivated attention, showed a trajectory similar to that reported in animal models. In contrast, we did not detect incubation of subjective cue-induced craving. Thus, the objective electroencephalographic measure may possibly be a better indicator of vulnerability to cue-induced relapse than subjective reports of craving, although this hypothesis must be empirically tested. These results suggest the importance of deploying intervention between 1 month and 6 months of abstinence, when addicted individuals may be most vulnerable to, and perhaps least cognizant of, risk of relapse.
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