Abstract：
BACKGROUND: Understanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments using neurobehavioral approaches require many trials or events of interest for statistical analysis, but the pharmacokinetics of most opioids limit dosing in humans.
OBJECTIVE: This experiment characterized the effects of repeated infusions of the ultra-short acting opioid remifentanil in people with OUD and physical opioid dependence.
METHODS: An inpatient study using a within-subjects, single-blind, escalating, within-session, pre-post design was conducted. Seven (3 female) subjects were maintained on oral oxycodone (40-60 mg, 4x/day = 160-240 total mg/day) for seven days prior to the dose-ranging session. Subjects received infusions of three ascending remifentanil doses (0.03, 0.1, 0.3 mcg/kg/infusion in 2 subjects; 0.1, 0.3, 1.0 mcg/kg/infusion in 5 subjects) every minute for 40 min per dose, with infusions administered over 5 s to model naturalistic delivery rates. End tidal carbon dioxide, respiration rate, oxygen saturation (SpO2) and heart rate were measured continuously. Blood pressure (BP), pupil diameter and self-reported drug effects were measured every 5 min.
RESULTS: Pupil diameter, SpO2 and systolic BP decreased, and ratings on prototypic subjective effects questionnaire items increased, as a function of remifentanil dose. The number of infusions held because of sedation or physiological parameters exceeding predetermined cutoffs also increased with dose.
CONCLUSIONS: This experiment established doses and procedures for the safe delivery of rapid, repeated remifentanil infusions to individuals with OUD and physical fentanyl dependence, which can be applied to the mechanistic study of opioid use decisions.
OBJECTIVE: This experiment characterized the effects of repeated infusions of the ultra-short acting opioid remifentanil in people with OUD and physical opioid dependence.
METHODS: An inpatient study using a within-subjects, single-blind, escalating, within-session, pre-post design was conducted. Seven (3 female) subjects were maintained on oral oxycodone (40-60 mg, 4x/day = 160-240 total mg/day) for seven days prior to the dose-ranging session. Subjects received infusions of three ascending remifentanil doses (0.03, 0.1, 0.3 mcg/kg/infusion in 2 subjects; 0.1, 0.3, 1.0 mcg/kg/infusion in 5 subjects) every minute for 40 min per dose, with infusions administered over 5 s to model naturalistic delivery rates. End tidal carbon dioxide, respiration rate, oxygen saturation (SpO2) and heart rate were measured continuously. Blood pressure (BP), pupil diameter and self-reported drug effects were measured every 5 min.
RESULTS: Pupil diameter, SpO2 and systolic BP decreased, and ratings on prototypic subjective effects questionnaire items increased, as a function of remifentanil dose. The number of infusions held because of sedation or physiological parameters exceeding predetermined cutoffs also increased with dose.
CONCLUSIONS: This experiment established doses and procedures for the safe delivery of rapid, repeated remifentanil infusions to individuals with OUD and physical fentanyl dependence, which can be applied to the mechanistic study of opioid use decisions.
摘要：
背景：了解药物使用决定的机制将为开发阿片类药物使用障碍（OUD）的治疗方法提供信息。使用神经行为方法的决策实验需要许多试验或感兴趣的事件进行统计分析，但是大多数阿片类药物的药代动力学限制了人体的剂量。
目的：本实验研究了反复输注超短效阿片类药物瑞芬太尼对OUD患者和身体阿片类药物依赖患者的影响。
方法：一项住院研究，使用受试者内部，单盲,不断升级,会内,进行了岗前设计。7名（3名女性）受试者口服羟考酮（40-60毫克，4x/天=160-240总mg/天），在剂量范围疗程之前的7天。受试者每分钟接受三个递增瑞芬太尼剂量的输注（2名受试者为0.03、0.1、0.3mcg/kg/输注；5名受试者为0.1、0.3、1.0mcg/kg/输注），每剂40分钟，输注超过5s以模拟自然分娩率。潮气末二氧化碳，呼吸频率,连续测量血氧饱和度(SpO2)和心率。血压(BP),每5分钟测量瞳孔直径和自我报告的药物作用。
结果：瞳孔直径，SpO2和收缩压下降，原型主观效应问卷项目的评分有所提高，作为瑞芬太尼剂量的函数。由于镇静或生理参数超过预定截止值而保持的输注次数也随着剂量而增加。
结论：本实验建立了快速，对OUD和身体芬太尼依赖的个体重复瑞芬太尼输注，可应用于阿片类药物使用决策的机理研究。
目的：本实验研究了反复输注超短效阿片类药物瑞芬太尼对OUD患者和身体阿片类药物依赖患者的影响。
方法：一项住院研究，使用受试者内部，单盲,不断升级,会内,进行了岗前设计。7名（3名女性）受试者口服羟考酮（40-60毫克，4x/天=160-240总mg/天），在剂量范围疗程之前的7天。受试者每分钟接受三个递增瑞芬太尼剂量的输注（2名受试者为0.03、0.1、0.3mcg/kg/输注；5名受试者为0.1、0.3、1.0mcg/kg/输注），每剂40分钟，输注超过5s以模拟自然分娩率。潮气末二氧化碳，呼吸频率,连续测量血氧饱和度(SpO2)和心率。血压(BP),每5分钟测量瞳孔直径和自我报告的药物作用。
结果：瞳孔直径，SpO2和收缩压下降，原型主观效应问卷项目的评分有所提高，作为瑞芬太尼剂量的函数。由于镇静或生理参数超过预定截止值而保持的输注次数也随着剂量而增加。
结论：本实验建立了快速，对OUD和身体芬太尼依赖的个体重复瑞芬太尼输注，可应用于阿片类药物使用决策的机理研究。
