Risks of Cannabis Use Among Veterans on Long-term Opioid Therapy

背景：尽管普通人群中大麻的使用越来越多， 与使用相关的潜在危害。在随机对照试验中， 药物对疼痛的管理，不良事件包括头晕，镇静，意识模糊，丧失， 平衡感恶心呕吐和幻觉这些副作用表明， 与阿片类药物-这也会导致，头晕，镇静，混乱，呼吸抑制，恶心，呕吐和 便秘可能是特别有害的。老年退伍军人，以及那些有潜在的呼吸和心脏 在某些情况下，阿片类药物和大麻联合使用的不良反应风险可能更高。另 一方面，一些生态研究表明，以州为基础的娱乐合法化可能与一个 减少阿片类药物相关死亡。因此，通过减少类阿片的使用， 减少呼吸抑制和过量的风险。然而，生态学研究考察了 阿片类药物相关死亡的合法化并没有告知我们对联合使用 大麻和阿片类药物对个人健康的影响。了解大麻与海洛因混合使用的影响 阿片类药物对个体患者的影响至关重要。目前没有证据可供参考 VA关于接受阿片类药物的慢性疼痛患者使用大麻的指南。 意义：虽然大麻的使用在患有慢性疼痛的退伍军人中很常见，但其风险或益处 长期阿片类药物治疗（LTOT）的退伍军人中使用大麻的情况尚不清楚。这一提议直接 响应VA实践指南和HSR&D优先领域确定的研究差距，重点是 “研究与老年退伍军人和退伍军人长期阿片类药物治疗相关的安全性和有效性问题 精神健康（非疼痛）状况”。我们的建议也是对HSR&D优先领域的回应： “使用数据挖掘策略评估LTOT队列研究的可行性。 创新：解决文献中关于大麻使用的潜在危害（或益处）的空白 在长期阿片类药物治疗的患者中，我们提出了一种创新的方法来构建队列， 结合尿液药物筛查数据、文本处理算法（由我们的团队开发）和国家VA 和医疗保险数据对暴露状态进行分类（伴随使用大麻加阿片类药物vs. 大麻），以实现以下目标： 具体目标：目标1：研究大麻使用与全因性精神分裂症结局的相关性。 长期使用阿片类药物的≥18岁退伍军人的死亡率。目标2：研究 大麻使用对全因死亡率的主要结局和住院治疗的次要结局的影响 在≥65岁接受LTOT的退伍军人中，患有慢性阻塞性肺病、充血性心力衰竭或 睡眠呼吸暂停目的3：研究大麻与全因死亡率的主要结局的相关性， 任何住院、跌倒相关损伤、任何损伤和因情绪住院的次要结局 在接受LTOT的≥65岁退伍军人中发生的疾病。 方法：我们将利用VA数据源，并使用从病程记录、尿液 毒理学数据以及国家VA和Medicare管理数据，以回答临床相关问题。我们 将使用倾向评分方法来比较大麻使用者和非使用者的一年结果。 下一步：下一步包括向VA研究人员和临床和 业务领导者。研究结果将为VA指南和临床实践提供信息。

Background: Despite increasing cannabis use among the general population, very little data exists on potential harms associated with use. In randomized controlled trials examining the effect of THC-based pharmaceuticals on the management of pain, adverse events included dizziness, sedation, confusion, loss of balance, nausea, vomiting, and hallucination. These side effects suggest that cannabis used in combination with opioids—which also cause, dizziness, sedation, confusion, respiratory depression, nausea, vomiting and constipation—may be particularly harmful. Older Veterans, and those with underlying respiratory and cardiac conditions, may be at higher risk of adverse effects from combined opioid and cannabis use. On the other hand, several ecological studies suggest that state-based recreational legalization may be associated with a decrease in opioid related deaths. Thus, it is plausible that cannabis use, by reducing the use of opioids, reduces respiratory depression and the risk of overdose. However, ecological studies examining the effect of legalization on opioid related deaths do not inform our understanding of the effects of combined use of cannabis and opioids on individual health. Understanding the effects of the combined use of cannabis and opioids on individual patient outcomes is critically important. No evidence base is currently available to inform VA guidelines on cannabis use among chronic pain patients who receive opiates. Significance: Although cannabis use is common among Veterans with chronic pain, the risk or benefits of cannabis use among Veterans on long-term opioid therapy (LTOT) is unknown. This proposal is directly responsive to research gaps identified by VA practice guidelines and the HSR&D priority area focused on “Studying safety and efficacy issues related to long-term opioid therapy among aging Veterans and Veterans with mental health (non-pain) conditions”. Our proposal is also responsive to the HSR&D priority area: “Assessing the feasibility of LTOT cohort studies using data-mining strategies.” Innovation: To address the gaps in the literature on the potential harms (or benefits) of cannabis use among patients on long-term opioid therapy, we propose an innovative approach to cohort construction using a combination of urine drug screen data, text processing algorithms (developed by our team), and national VA and Medicare data to categorize exposure status (concomitant cannabis plus opioid vs. opioid without cannabis) to address the following aims: Specific Aims: Aim 1: To examine the association of cannabis use on the outcome of all-cause mortality among Veterans ≥18 years-old who use long-term opioids. Aim 2: To examine the association of cannabis use on the primary outcome of all-cause mortality and the secondary outcomes of hospitalization among Veterans ≥65 years-old on LTOT with chronic obstructive lung disease, congestive heart failure or sleep apnea. Aim 3: To examine the association of cannabis on the primary outcome of all-cause mortality and the secondary outcomes of any hospitalization, fall-related injury, any injury, and hospitalization for mood disorders among Veterans ≥65 years-old on LTOT. Methodology: We will leverage VA data sources and use data extracted from progress notes, urine toxicology data, and national VA and Medicare administrative data to answer a clinically relevant question. We will use propensity score methods to compare one-year outcomes among cannabis users and non-users. Next Steps: Next steps include dissemination of the findings to VA researchers and clinical and operational leaders. Study findings will be informative to VA guidelines and clinical practice.