Highs or Lows? Evaluating the Benefits and Consequences of Medical Marijuana Use in Older Adults with Chronic Pain and Opioid Use

随着美国的老龄化，到2019年，大约29%的美国人口将达到55岁或以上； 在接下来的35年里，50多岁的人口将增加一倍以上。随着个人年龄的增长，慢性病的患病率 疼痛增加；最近的报告表明，大约50%的老年人经历令人烦恼的疼痛，并且 疼痛的患病率在50-65岁之间达到顶峰。历史上，阿片类药物一直是慢性阻塞性肺疾病的主要治疗方法。 然而，它们对长期治疗疼痛的疗效有限。此外，在过去十年中，阿片类药物的比率 使用障碍和与阿片类药物相关的过量以惊人的速度增加，导致全国流行。 耐受性的发展、新陈代谢的改变和不可预测的敏感性也会增加使用 这些药物，特别是在病情使其容易产生不良后果的老年人中。 虽然大麻(MJ)的止痛作用早在几个世纪前就已为人所知，但美国国家科学院 最近有科学报道称，有“确凿或确凿的证据”表明，大麻素对癌症有效 对于慢性疼痛的治疗，其附表一的状态排除了其在主流医学中的使用。然而，由于 大多数州现在已经通过了医用大麻(MMJ)法律，许多州对MMJ的使用开放，而且 老年人使用MJ的比例继续增长。到目前为止，大多数研究都集中在 青少年/青壮年用户的娱乐性MJ使用，据报告他们的认知能力减退； 然而，越来越多地将MJ用于医疗目的的老年人的后果仍不清楚。 最近来自老年MMJ患者的试点数据显示，药物使用显著减少，尤其是 阿片类药物的使用，在MMJ治疗3个月后，与证明合法的州的研究一致 MMJ报告说，开出的处方和阿片类药物相关的过量都较少。此外，我们观察到了显著的 在认知能力、临床状态和大脑激活的“正常化”模式方面的改善。我们建议 一项新的纵向研究量化了MMJ产品对多个领域的影响，包括 50-75岁老年人的药物使用(如阿片类药物)和疼痛。此外，我们将量化MMJ的影响 使用多模式神经成像对认知功能和临床状态以及神经生物标记物的应用， 以前没有在老年人身上进行过评估。在启动之前，患者将在基线上进行评估 MMJ治疗，并在治疗3、6和12个月后；将完成分析以确定是否有益 与有害的大麻素组合/比率。与之匹配的一组患有慢性疼痛的老年人 将MMJ治疗设为对照组。必须确定在什么情况下MMJ可能会 对这一弱势群体是有益的还是有害的。这个项目填补了一个关于正面和负面的重要空白 对患有慢性疼痛的阿片类药物维持性老年人使用MMJ的后果，告知公共卫生政策 与阿片类药物危机和MMJ治疗结果有关，并为MMJ的临床试验提供了基础 这群人。

With the “graying of America,” approximately 29% of the United States population will be 55 or older in 2019; over the next 35 years, the 50+ population will more than double. As individuals age, the prevalence of chronic pain increases; recent reports indicate that approximately 50% of older adults experience bothersome pain, and the prevalence of pain peaks during ages 50-65. Historically, opioids have been the primary therapy for chronic pain, however, they have limited efficacy for long-term treatment. Further, over the past decade, rates of opioid use disorders and opioid-related overdoses have increased at an alarming rate, resulting in a national epidemic. The development of tolerance, altered metabolism and unpredictable sensitivity also increase the risk of using these medications, especially in older adults with conditions making them prone to adverse consequences. Although the analgesic effects of marijuana (MJ) have been known for centuries, and the National Academy of Sciences recently reported there is “conclusive or substantial evidence” that cannabinoids are efficacious for the treatment of chronic pain, its Schedule I status has precluded its use in mainstream medicine. However, as the majority of states have now passed medical marijuana (MMJ) laws, many are open to MMJ use, and the proportion of older adults using MJ continues to grow. Most research thus far has focused on the impact of recreational MJ use among adolescent/young adult users, in whom cognitive decrements have been reported; however, consequences in older adults who are increasingly using MJ for medical purposes remain unknown. Recent pilot data from older MMJ patients demonstrated significant reductions in medication use, notably the use of opioids, after 3 months of MMJ treatment, aligned with studies demonstrating that states with legalized MMJ report both fewer prescriptions written and opioid-related overdoses. Additionally, we observed significant improvements in cognitive performance, clinical state, and ‘normalized’ patterns of brain activation. We propose a novel longitudinal study to quantify the impact of ‘real world’ MMJ products on multiple domains, including medication use (e.g. opioids) and pain in older adults aged 50-75. Further, we will quantify the impact of MMJ use on cognitive function and clinical state as well as neurobiologic markers using multimodal neuroimaging, which have not previously been assessed in older adults. Patients will be evaluated at baseline, prior to initiating MMJ treatment, and after 3, 6, and 12 months of treatment; analyses will be completed to determine beneficial vs detrimental cannabinoid combinations/ratios. A matched group of older adults with chronic pain not seeking MMJ treatment will serve as a control group. It is imperative to determine under which conditions MMJ may be helpful or harmful in this vulnerable population. This project fills an important gap regarding positive and negative consequences of MMJ use in opioid-maintained older adults with chronic pain, informs public health policy related to the opioid crisis and MMJ treatment outcomes, and provides a foundation for a clinical trial of MMJ in this population.