Enhancing Exercise and Psychotherapy to Treat Comorbid Addiction and Pain for ImprovingAdherence to Medication Assisted Treatment in Opioid Use Disorders

项目摘要 据估计，美国有超过2030万成年人患有物质使用障碍（SUD）; 200万美国人患有涉及处方阿片类药物的阿片类药物使用障碍（OUD）， 都有涉及海洛因的吸毒过量包括海洛因在内的非法阿片类药物过量死亡人数， 从2011年到2015年，合成阿片类药物在美国增加了两倍。 在每年处方阿片类药物滥用的成瘾治疗中，50%-60%报告共病慢性疼痛，80% 报告说疼痛会导致复发高复发率并不奇怪，因为药物滥用可能 在需要参与的相同大脑区域引起不利的结构和功能性大脑变化， 开始恢复并保持禁欲。运动已被证明可以减少对物质的渴望， 抑郁和焦虑，并可能有助于减少美沙酮和抗精神病药物引起的体重增加 治疗;以及，运动，特别是在较高强度下，可产生改善疼痛的止痛效果 对慢性疼痛患者的治疗。运动可能通过增加生长和脑源性神经营养因子来起作用。 刺激内源性多巴胺能、阿片样物质能和多巴胺能系统的因子，这些系统反过来增强 可塑性，学习和记忆。这些影响可能有助于修复大脑结构和功能的变化 造成的物质滥用和慢性疼痛，并帮助“抵消”寻求奖励和渴望的物质， 改善身心健康。然而，大多数住院药物治疗方案目前并不 提供一个结构化的锻炼计划。我们开发了一种“辅助”运动技术， 患者参与和机械辅助，以帮助患者比他们的自愿率更快地踩踏板。我们 先前已经证明，在固定自行车上进行“辅助”锻炼可以全面改善运动功能， 皮质和皮质下大脑区域的功能和活动增加与神经激活一致 在帕金森病患者中应用多巴胺激动剂后的模式，表明“辅助”运动 可能在调节大脑中的多巴胺水平。此外，我们已经表明，“辅助”自行车提高 中风患者的运动功能和恢复。我们还开发了一种新的自我调节/认知 行为治疗（CBT）计划，共同解决阿片类药物成瘾和疼痛（STOP），这表明 对门诊患者的疼痛耐受性、渴望和日常活动中的功能参与的功效。响应于 RFA-AT-19-006，我们建议采取多阶段优化策略（MOST）方法来完善我们的 与我们的社区合作伙伴（R61阶段）进行干预方案和可行性测试，并评估 运动和I-STOP（为住院患者修改的STOP）作为药物辅助治疗的后续治疗的效果 在住院治疗计划中登记的患有OUD和慢性疼痛的成人中进行治疗（MAT）， 减少药物渴望和疼痛，增加MAT（美沙酮，丁丙诺啡）的依从性（R33阶段）。

PROJECT SUMMARY Over 20.3 million adults in the U.S. are estimated to have a substance use disorder (SUD); and, an estimated 2 million Americans have had an opioid use disorder (OUD) involving prescription opioids and about 600,000 have had an OUD involving heroin. The number of overdose deaths from illicit opioids including heroin and synthetic opioids has tripled from 2011 to 2015 in the U.S. Among the more than half-million adults entering addiction treatment for prescription opioid abuse every year, 50%-60% report co-morbid chronic pain and 80% report that pain triggers relapse. High rates of relapse are not surprising because substance misuse may cause adverse structural and functional brain changes in the same brain regions that need to be engaged to initiate recovery and maintain abstinence. Exercise has been shown to reduce substance cravings and reduce depression and anxiety and may help reduce weight gain induced by methadone and anti-psychotic drug treatments; and, exercise, particularly at higher intensities, may produce an analgesic effect improving pain measures in chronic pain patients. Exercise may act by increasing growth and brain-derived neurotrophic factors that stimulate endogenous dopaminergic, opioidergic and serotoninergic systems that, in turn, enhance plasticity, learning and memory. These effects may help repair the structural and functional brain changes caused by substance abuse and chronic pain and help “offset” reward seeking and craving of substances while improving physical and mental health. However, most residential drug treatment programs do not currently offer a structured exercise program. We have developed an ‘assisted’ exercise technology that enables active patient engagement and mechanical assistance to help patients pedal faster than their voluntary rates. We have previously shown that ‘assisted’ exercise on a stationary cycle provides global improvements in motor function and increased activity in cortical and subcortical brain regions consistent with neural activation patterns after applying a dopamine agonist in Parkinson’s disease patients, suggesting that ‘assisted’ exercise may be modulating dopamine levels in the brain. In addition, we have shown that ‘assisted’ cycling improves motor function and recovery in stroke patients. We have also developed a novel self-regulation/cognitive behavioral therapy (CBT) program that co-addresses opioid addiction and pain (STOP), which has shown efficacy on pain tolerance, cravings and functional engagement in daily activities in outpatients. In response to RFA-AT-19-006, we propose to take a multi-phase optimization strategy (MOST) approach to refining our intervention protocols and testing feasibility with our community partners (R61 Phase) and evaluating the effects of exercise and I-STOP (STOP modified for inpatients) as adjunctive treatments to Medication Assisted Treatment (MAT) in adults with an OUD and chronic pain enrolled in residential treatment programs to decrease drug cravings and pain and increase adherence to MAT (methadone, buprenorphine) (R33 Phase).