Abuse-Related Effects of Opioids and Adjuvant Drug Used by Chronic Pain Patients

慢性疼痛患者使用阿片类药物和辅助药物的滥用相关影响

• 批准号: 7878043
• 负责人: JAMES P. ZACNY
• 金额: $ 32.56万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-24 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7878043
• 关键词: Abate; Acute; Adjuvant; Adverse effects; Alprazolam; Analgesics; Anticonvulsants; Anxiety; Anxiety Disorders; Attention; Benzodiazepines; Carisoprodol; Carnrick brand of metaxalone; Case Study; Chronic; Clinical; Clinical Data; Clinical Research; Clinical Trials; Communities; Comorbidity; Confounding Factors (Epidemiology); Controlled Study; Crossover Design; Data; Diagnostic; Disease; Dose; Double-Blind Method; Drug Interactions; Drug Prescriptions; Drug usage; Drug user; Elan brand of zonisamide; Epidemiologic Studies; Epidemiology; Euphoria; Exercise; Face; Future; Heroin; Human; Laboratories; Laboratory Study; Literature; Malignant Neoplasms; Measures; Medical; Mental disorders; Methadone; Methodology; Mood Disorders; Muscle relaxants; Nature; Non-Malignant; Opioid; Oral; Oxazepam; Oxycodone; Pain; Patients; Pharmaceutical Preparations; Physicians; Placebo Control; Placebos; Population; Prevalence; Property; Public Health; Quality of life; Recording of previous events; Recreational Drugs; Relative (related person); Research; Rewards; Risk; Schedule; Seizures; Serax; Series; Signal Transduction; Site; Spasm; Substance abuse problem; Syndrome; Time; Treatment Protocols; United States; Work; Xanax; addiction; base; chronic pain; clinically relevant; critical period; design; interest; meetings; metaxalone; neuronal cell body; phrases; pre-clinical; preclinical study; pregabalin; prescription opioid; prescription opioid abuse; research study

DESCRIPTION (provided by applicant): Non-medical use and abuse of prescription opioids is a substantial public health problem in the US. It is not clear what the prevalence is of prescription opioid abuse in patients who are prescribed opioids for chronic pain not related to cancer (i.e., chronic nonmalignant pain, CNMP), but some studies suggest the prevalence is more than minimal. Many CNMP patients are prescribed other CNS-active drugs, in addition to opioids, that serve as adjuvants to either augment pain relief or to treat comorbid psychiatric disorders (e.g., anxiety). Whether these other drugs alter the abuse liability-related effects of opioids has not been studied in humans. Drug interaction studies investigating this notion are warranted because there is evidence in the scientific literature to suggest that some adjuvant drugs when taken in combination with a prescribed opioid might generate greater abuse liability-related effects than the prescription opioid alone. The current application consists of three studies: using an abuse liability assessment methodology we will examine the interactions of oral oxycodone, a drug prescribed for CNMP and that has abuse liability, and two adjuvant drugs from each of three different classes of drugs (muscle relaxants [specific drugs: carisoprodol, metaxalone], benzodiazepines [alprazolam, oxazepam], and anticonvulsants [pregabalin, zonisamide]) in recreational drug users. In each study, one adjuvant will be termed the study drug adjuvant (the drug that we hypothesize will, in combination with oxycodone, produce greater abuse liability-related effects than oxycodone alone), and the other will be termed the comparator negative control adjuvant. Each study will include studying two doses of the study drug adjuvant and one dose of the comparator negative control adjuvant, alone and in combination with oxycodone, using a double-blind, placebo-controlled, crossover design. Key endpoints are abuse liability-related subjective effects (e.g., drug liking). We hypothesize that carisoprodol, alprazolam, and pregabalin, when combined with oxycodone, will produce greater abuse liability-related subjective effects than oxycodone alone. If the hypotheses are supported, we would urge physicians to exercise special caution when prescribing these adjuvants to CNMP patients on long-term opioid therapy, especially those with histories of substance abuse. Other adjuvants, efficacious for a given indication, but devoid of abuse liability-related effects, might be more suitable alternatives. This application consists of a series of clinical laboratory studies to examine a potential modulator of abuse- related effects of prescription opioids that has relevance to the treatment of chronic nonmalignant pain. Our application seeks to determine if different adjuvant drugs that are commonly co-prescribed along with prescription opioids to chronic nonmalignant pain patients produce greater abuse liability-related effects (drug liking) than the prescription opioid alone. The studies have public health ramifications: if an adjuvant drug (e.g., muscle relaxant A) in combination with a prescription opioid produces greater abuse liability-related effects than the opioid alone, such information would be important for clinicians to have in that alternative efficacious adjuvant that do not show such enhancement (e.g., muscle relaxant B) would be the preferred drug to prescribe when treating chronic nonmalignant pain patients.

描述（由申请人提供）：在美国，非医学使用和滥用处方阿片类药物是一个实质性的公共卫生问题。目前尚不清楚在与癌症无关的慢性疼痛的患者中处方阿片类药物滥用的患病率是什么（即慢性非恶性疼痛，CNMP），但一些研究表明，这种患病率远远超过最小。除阿片类药物外，许多CNMP患者还处方了其他CNS活性药物，这些药物是增加疼痛缓解或治疗合并症精神病（例如焦虑症）的辅助药物。其他药物是否改变了阿片类药物与滥用责任的作用，尚未在人类中研究。有必要对研究这种概念进行的药物相互作用研究，因为科学文献中有证据表明，与处方的阿片类药物结合使用时，某些辅助药物可能会产生与单独处方阿片类药物相比，可能会产生更大的与滥用责任的作用。 The current application consists of three studies: using an abuse liability assessment methodology we will examine the interactions of oral oxycodone, a drug prescribed for CNMP and that has abuse liability, and two adjuvant drugs from each of three different classes of drugs (muscle relaxants [specific drugs: carisoprodol, metaxalone], benzodiazepines [alprazolam, oxazep​​am], and anticonvul​​sants [pregabalin，Zonisamide]）在休闲吸毒者中。在每项研究中，一项辅助药物将被称为研究药物辅助（我们假设将与羟考酮结合使用的药物，与单独使用羟考酮产生更大的滥用责任作用），另一种将称为比较剂负面对照辅助剂。每项研究都将包括研究两次研究药物辅助剂和一种比较剂阴性对照佐剂，单独并与羟考酮结合使用，使用双盲，安慰剂对照，交叉设计。关键终点是与滥用责任相关的主观效应（例如，毒品喜欢）。我们假设Carisoprodol，Alprazolam和Pregabalin与羟考酮相结合时，与单独使用羟考酮相比会产生更大的与滥用责任相关的主观效应。如果支持假设，我们将敦促医生在对CNMP患者开出长期阿片类药物疗法的情况下，特别是那些患有药物滥用病史的辅助患者时要特别谨慎。其他佐剂，有效地表明给定的指示，但没有与虐待责任相关的效果，可能是更合适的选择。该应用程序包括一系列临床实验室研究，以检查与慢性非恶性疼痛相关的处方阿片类药物相关作用的潜在调节剂。我们的应用程序旨在确定通常与单独的处方阿片类药物相比，与慢性非恶性疼痛患者的处方阿片类药物以及处方阿片类药物以及对慢性非恶性疼痛患者的处方阿片类药物的影响是否更大的辅助药物产生更大的辅助药物。这项研究具有公共卫生的影响：如果辅助药物（例如，肌肉放松剂A）与处方阿片类药物相比，与单独的阿片类药物相比会产生更大的与虐待责任相关的作用，那么此类信息对于临床医生而言对替代有效的辅助药物对这种增强的疗效很重要（例如，在肌肉放松患者中都会表现出较高的痛苦，因此在肌肉中不适合使用肌肉。