Assessing Benefits and Harms of Cannabis and Cannabinoid Use Among a Cohort of Cancer Patients Treated in Community Oncology Clinics

摘要 癌症患者遭受与癌症和癌症治疗相关的多种虚弱症状的折磨， 其中许多并不能通过处方药缓解。为了控制这些症状，许多人 患者正在转向大麻，最近估计癌症患者中使用大麻的人数从 24-40%，主要用于缓解身体和神经精神症状，尽管有有限的益处和证据 不确定的风险。这在一定程度上是因为随着更多的州将大麻使用合法化，大麻的可获得性增加。这个 扩大大麻市场，法规多种多样，产品标准有限，营销限制很少， 导致市场上充斥着各种各样的产品类型(例如，烟熏大麻、蒸气、可食用产品、局部用药) 具有不可预测的大麻素浓度，通常超过治疗效益(THC&GT；15%)。这些 产品与急性醉酒效应和长期不良反应有关。此外，货柜码头处理费和 CBD是主要的大麻类化合物，可能对肝脏有毒性，影响化疗的代谢，并导致 药物的相互作用可能会增强化学毒性。此外，大麻的免疫抑制作用可能 抑制免疫反应，改变免疫检查点抑制剂的疗效。尽管如此，患者 一般报告说，大麻可以改善癌症相关症状。临床疗效的最新证据 大麻好坏参半，而且往往没有定论，这主要是由于样本量较小和/或横断面数据。至 更好地了解在癌症治疗期间使用大麻和大麻素的好处和风险，严格 对记录大麻使用细节的患者队列的纵向研究(即产品类型、频率、 大麻素的比例和效力，以及使用模式)是必要的。我们的目标是通过合作实现这一目标 与国家癌症研究所社区肿瘤学研究计划(NCORP)合作，一个全国性的 社区肿瘤诊所。我们将招募2000名新诊断的乳腺癌患者作为样本。 癌症、非小细胞肺癌、结直肠癌、黑色素瘤或非霍奇金淋巴瘤，以评估 在治疗期间使用大麻和大麻素的益处和风险。参与者将每月在线完成 为期12个月的调查，以评估与癌症有关的症状和严重程度，以及详细的大麻和 大麻类药物的使用。这将使我们能够(1)描述成人癌症患者的纵向使用模式 以及个人、临床和社区因素对这些模式的影响；以及(2) 确定使用该药对癌症和治疗相关症状(如恶心)的潜在益处和危害 呕吐、焦虑、神经病)。我们还将评估潜在的药代动力学和药效学效应。 通过收集和分析在癌症治疗中的应用以及炎性和毒性标志物的变化 肺癌患者亚组中的生物胺类药物。这些数据将使我们更好地了解 大麻和大麻素使用的异质性模式与癌症症状的时间关系 管理；将对未来癌症护理临床试验的设计做出重大贡献的信息。

SUMMARY Cancer patients suffer from a multitude of debilitating symptoms associated with cancer and cancer treatment, many of which are not relieved with prescription medications. In hopes of managing these symptoms, many patients are turning to cannabis, with recent estimates of cannabis use among cancer patients ranging from 24-40%, primarily for physical and neuropsychiatric symptom relief, despite limited evidence of benefits and uncertain risks. This is, in part, due to increased availability of cannabis as more states legalize use. The expanding cannabis market, with varying regulations, limited product standards and few marketing restrictions, has resulted in a marketplace filled with diverse product types (e.g., smoked cannabis, vapes, edibles, topicals) with unpredictable cannabinoid concentrations, often exceeding that of therapeutic benefit (THC>15%). These products are associated with acute intoxicating effects and long-term adverse effects. Furthermore, THC and CBD, the primary cannabinoids, may be hepatotoxic, affect the metabolism of chemotherapy, and result in drug interactions that could enhance chemotoxicity. Furthermore, cannabis’ immunosuppressive effects could dampen immune responses and alter the efficacy of immune checkpoint inhibitors. Despite this, patients generally report that cannabis improves cancer-related symptoms. Current evidence for clinical benefits of cannabis is mixed and often inconclusive, largely due to small sample sizes and/or cross-sectional data. To better understand the benefits and risks of cannabis and cannabinoid use during cancer treatment, rigorous longitudinal studies of patient cohorts that document details of cannabis use (i.e. product type, frequency, cannabinoid ratios and potency, and patterns of use) are needed. We aim to achieve this goal by collaborating with the National Cancer Institute Community Oncology Research Program (NCORP), a national network of community oncology clinics. We will recruit a sample of 2000 newly diagnosed cancer patients with breast cancer, non-small cell lung cancer, colorectal cancer, melanoma, or non-Hodgkin lymphoma, to assess the benefits and risks of cannabis and cannabinoid use during treatment. Participants will complete monthly online surveys for 12 months to assess cancer-related symptoms and severity, as well as detailed cannabis and cannabinoid use. This will allow us to (1) describe the longitudinal patterns of use among adult cancer patients during treatment and the effect of individual, clinical and community-level factors on these patterns, and (2) determine the potential benefits and harms of use on cancer and treatment-related symptoms (e.g., nausea/ vomiting, anxiety, neuropathy). We will also assess potential pharmacokinetic and pharmacodynamic effects of use with cancer treatment and changes in inflammatory and toxicity markers by collecting and analyzing biospecimens in a subgroup of lung cancer patients. These data will provide a better understanding of the temporal relationship between heterogeneous patterns of cannabis and cannabinoid use and cancer symptom management; information that will contribute significantly to the design of future clinical trials in cancer care.