6-week trial of oxytocin for co-occurring cocaine and opioid use disorders

与一般人群相比，退伍军人中物质使用障碍的发生率较高 受心理社会因素的影响很大-例如难以重新融入 由于避免使用重要的支持系统，平民的生命受到威胁-导致不成比例的 未满足的成瘾治疗需求增加。那些同时使用可卡因和海洛因的人 死亡率是普通人群的14.3倍。30-60%的患者接受 美沙酮维持治疗（MMT）用于阿片类药物使用障碍，积极使用可卡因。 目前还没有批准的精神药理学治疗可卡因的使用 疾病，从MMT项目和重要的心理社会治疗的辍学率是 高达80%。更重要的是，可卡因的使用，与其他药物相比， 特别是由社会压力驱动，可卡因与高反应性有关， 下丘脑-垂体-肾上腺（HPA）轴。临床前和初步临床研究结果表明， 催产素是一种哺乳动物神经肽， 直接的抗成瘾作用，提高心理社会治疗的参与度， 减弱可卡因使用障碍患者HPA轴的高反应性。这是一 对50名积极使用可卡因的退伍军人进行的双盲、安慰剂对照临床试验 在阿片类药物治疗项目中也接受MMT，随机接受 催产素40 IU或安慰剂鼻内给药，每日两次，持续6周。主 结果衡量将是催产素在减少可卡因使用方面的有效性， 每周尿样中可卡因代谢物苯甲酰芽子碱的定量水平。 治疗反应的潜在机制将通过测量催产素的 a）改善与治疗提供者的治疗联盟（工作 联盟库存，客户和治疗师的形式）和出席现有的诊所运行 B）通过测量自身应激反应来减弱社会应激反应， 报告可卡因的渴望，心理生理压力的措施，和唾液皮质醇， 特里尔社会压力测试总而言之，退伍军人和 在成瘾的流行程度，严重程度和成功的干预平民在很大程度上是驱动 退伍军人的社交回避率和创伤后应激症状率更高。 这项研究将独特地将联合收割机精神药理学和循证医学结合起来， 旨在减少可卡因使用、改善治疗 参与，并防止与压力相关的可卡因使用的退伍军人与合作， 发生可卡因和阿片类药物使用障碍接受MMT。

High rates of substance use disorders in Veterans compared to the general population are heavily influenced by psychosocial factors – such as difficulty reintegrating into civilian life due to avoidance of vital support systems – leading to disproportionately elevated unmet addiction treatment needs. Those using both cocaine and heroin have mortality rates 14.3 times higher than the general population. 30-60% of patients receiving methadone maintenance therapy (MMT) for opioid use disorder actively use cocaine. There are currently no approved psychopharmacological treatments for cocaine use disorder, and drop-out rates from MMT programs and vital psychosocial treatments are as high as 80% for cocaine users. What’s more, cocaine use, compared to other drugs, is particularly driven by social stress, and cocaine is associated with hyperreactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Preclinical and pilot clinical findings suggest that administration of oxytocin, a mammalian neuropeptide, may have a multitude of direct anti-addiction effects, improve engagement in psychosocial treatments, and attenuate hyperreactivity of the HPA axis in patients with cocaine use disorder. This is a double-blinded, placebo-controlled, clinical trial of fifty Veterans with active cocaine use disorder, also receiving MMT in an opioid treatment program, randomized to receive either oxytocin 40 IU or placebo intranasally twice daily for six weeks. The primary outcome measure will be oxytocin’s effectiveness at reducing cocaine use as measured by quantitative levels of the cocaine metabolite, benzoylecgonine, in weekly urine samples. Potential mechanisms of treatment response will be evaluated by measuring oxytocin’s effectiveness at a) improving therapeutic alliance with treatment providers (Working Alliance Inventory, client and therapist forms) and attendance in existing clinic-run treatment components and b) attenuating social stress-reactivity by measuring self- reported cocaine craving, psychophysiological stress measures, and salivary cortisol in response to a Trier Social Stress Test. In sum, discrepancies between Veterans and civilians in addiction prevalence, severity, and successful intervention are largely driven by higher rates of social avoidance and posttraumatic stress symptoms among Veterans. This study will uniquely combine psychopharmacological and evidence-based psychosocial interventions targeted at reducing cocaine use, improving treatment engagement, and preventing stress-related cocaine use among Veterans with co- occurring cocaine and opioid use disorders receiving MMT.