Prescription Opioid Effects in Drug and Non-drug Abusers

描述（由申请人提供）：正如各种来源所反映的那样，处方阿片类药物的非医疗使用在美国继续升级。为了更好地理解这一全国性现象，我们实验室最近的工作已经开始表征处方阿片类药物在人类中的强化和主观效应。在我们之前的奖励期间进行的一项研究表明，口服羟考酮在药物滥用者和非药物滥用者中引起了相似的主观效应，但两组之间的自我给药模式因疼痛而不同。具体而言，非药物滥用者仅在经历实验性诱导疼痛时自行服用羟考酮，而滥用者无论疼痛状况如何均自行服用羟考酮。在我们实验室的另一项研究中，我们发现口服羟考酮和口服吗啡对依赖海洛因的人的效果是不同的，这些人一直在使用舌下丁丙诺啡。具体来说，羟考酮和吗啡的自我给药率都高于安慰剂，而吗啡的自我给药率则不受欢迎。此外，当直接比较吗啡和羟考酮的效果时，参与者选择自我服用羟考酮的比例明显高于口服吗啡。这一发现表明，对海洛因依赖者来说，口服羟考酮比吗啡更可取，而且更容易被滥用。羟考酮和吗啡的这种不对称关系是否也存在于慢性疼痛和非慢性疼痛的处方阿片类药物滥用个体中尚不清楚，因为这种直接比较尚未在相同的实验条件下进行研究。因此，本申请拟开展的研究将考察口服羟考酮和吗啡对4组持续舌下丁丙诺啡/纳洛酮的影响：无疼痛的海洛因滥用者、无疼痛的处方阿片类药物滥用者、滥用处方阿片类药物的慢性疼痛患者和未滥用处方阿片类药物的慢性疼痛患者。当试图全面了解疼痛和处方阿片类药物滥用之间的关系时，将最后一组参与者包括在内是至关重要的。通过纳入这组患者，我们可以开始理清处方阿片类药物滥用的问题在多大程度上与这些药物的药理学特性、是否存在临床疼痛以及是否存在药物滥用有关。受试者将继续服用三剂丁丙诺啡/纳洛酮舌下治疗（2/0.5 mg, 16/4 mg, 32/8 mg）。在丁丙诺啡/纳洛酮维持剂量不同的情况下，观察羟考酮和吗啡的相对强化作用。研究结果将为药物滥用文献和疼痛文献提供信息。

DESCRIPTION (provided by applicant): The non-medical use of prescription opioids continues to escalate in the United States, as reflected in a variety of sources. In order to better understand this national phenomenon, recent work in our laboratory has begun to characterize the reinforcing and subjective effects of prescription opioids in humans. A study conducted during our previous award period revealed that oral oxycodone elicited similar subjective effects in drug abusers and non-drug abusers, but the self-administration patterns differed between these two groups as a function of pain. Specifically, non-drug abusers only self-administered oxycodone when they experienced experimentally induced pain, while abusers self-administered oxycodone regardless of pain condition. In another study conducted in our laboratory under another grant, we found that the effects of oral oxycodone and oral morphine differed in heroin-dependent individuals who were maintained on sublingual buprenorphine. Specifically, both oxycodone and morphine were self-administered more than placebo using a drug versus drug self-administration choice procedure, yet morphine was not well liked. Further, when the effects of morphine and oxycodone were compared directly, participants chose to self-administer oral oxycodone significantly more than oral morphine. This finding suggests that when given orally, oxycodone was preferred over, and may be more likely to be abused than, morphine in heroin-dependent individuals. Whether or not this asymmetrical relationship between oxycodone and morphine also exists in prescription-opioid abusing individuals who are in chronic pain versus those who are not in chronic pain is unknown, as this direct comparison has not yet been investigated under the same experimental conditions. Therefore, the study proposed in the current application will examine the effects of oral oxycodone and morphine in 4 groups of participants who will be maintained on sublingual buprenorphine/naloxone: heroin abusers who are not in pain, prescription opioid abusers who are not in pain, patients with chronic pain who are abusing prescription opioids, and patients with chronic pain who are not abusing prescription opioids. It is vitally important to include this last group of participants when attempting to gain a complete picture of the relationship between pain and prescription-opioid abuse. By including this group of patients, we may begin to disentangle to what extent the problems of prescription opioid misuse are related to the pharmacological properties of these drugs, the presence or absence of clinical pain, and the presence or absence of drug abuse. Participants will be maintained on three doses of sublingual buprenorphine/naloxone (2/0.5 mg, 16/4 mg, 32/8 mg). The relative reinforcing effects of oxycodone and morphine will be tested under each sublingual buprenorphine/naloxone maintenance dose condition. Findings will inform both the substance abuse literature as well as the pain literature. PUBLIC HEALTH RELEVANCE: The misuse of prescription opioid medications among individuals with pain, as well as those without pain, is of significant concern to the public health of the nation. However, the study of prescription opioid abuse in different populations of patients is in its infancy. This study proposes to examine the relative abuse liability of 2 commonly prescribed opioids in 4 groups of participants who will be maintained on sublingual buprenorphine/naloxone: heroin abusers and who are not in pain, prescription opioid abusers who are not in pain, patients with chronic pain who are abusing prescription opioids, and patients with chronic pain who are not abusing prescription opioids.