Quetiapine Pharmacotherapy for Cannabis Dependence

描述（由申请人提供）：尽管公众的看法是良性的，但大麻使用障碍是一个重大的公共卫生问题。由于治疗大麻依赖的唯一现有循证临床策略是行为干预，因此开发安全有效的大麻依赖药物治疗是一个重要的未满足的公共卫生需求。大麻依赖的理想药物疗法是：1）对使用大麻的患者使用时安全且耐受性良好2）减少大麻摄入量并促进禁欲3）治疗大麻戒断症状。开发安全有效的药物治疗大麻依赖是一个重要的未满足的公共卫生需求。 奎替鲁是一种有效的非典型抗精神病药，通过阻断2A型血清素、2型多巴胺、1型组胺和肾上腺素能受体起作用，是一种有希望的物质使用障碍治疗方法。在动物模型中，奎替尼阻断了可卡因对奖赏的增强，这可能是由于它对多巴胺和非多巴胺神经传递的作用。奎替鲁的临床研究表明，对酒精和可卡因使用障碍的治疗有益。从概念上讲，奎替鲁的临床突出作用，即镇静，抗焦虑，情绪稳定和食欲刺激，与大麻戒断症状很好地匹配。最重要的是，由我们的研究小组进行的一项开放标签的剂量探索研究，确定了奎替利的耐受性良好，并与大麻使用的减少有关，这表明它是一种有前途的药物，值得在大麻依赖门诊患者中进一步研究。 拟议的研究项目是一项随机、双盲、安慰剂对照的临床试验，旨在评估奎替鲁治疗大麻依赖的疗效，为期12周。所有参与者将接受医疗管理，这是一种以药物依从性为重点的心理社会干预，旨在促进研究药物和其他研究程序的依从性，促进大麻和其他物质的戒断，并鼓励互助小组的参与。所有受试者都将收到代金券奖励，以鼓励他们依从研究访视、返还研究药物瓶和完成其他研究程序，目的是获得高度依从的样本。这项II期临床试验的目标是建立在我们有希望的开放标签试点研究结果的基础上，并使用禁欲启动模型在安慰剂对照的双盲条件下检查奎替鲁对参与者大麻消费的疗效，参与者将在研究开始时定期使用大麻，减少使用，然后实现禁欲。这些项目的具体目标是确定奎替洛尔在1）减少大麻使用和2）实现禁欲方面是否优于安慰剂上级。

DESCRIPTION (provided by applicant): Despite a benign public perception, marijuana use disorders represent a significant public health problem. Because the only existing evidenced-based clinical strategies for treating marijuana dependence are behavioral interventions, the development of safe and effective pharmacotherapy for marijuana dependence is an important unmet public health need. The ideal pharmacotherapy for marijuana dependence would: 1) be safe and well tolerated when administered to patients using marijuana~ 2) reduce marijuana intake and promote abstinence~ and 3) treat the symptoms of marijuana withdrawal. The development of safe and effective pharmacotherapy's for marijuana dependence is an important unmet public health need. Quetiapine, an effective atypical antipsychotic that acts by blocking serotonin type 2A, dopamine type 2, histamine type 1, and adrenergic receptors, is a promising treatment for substance use disorders. In animal models, quetiapine blocks the enhancement of reward by cocaine, which is likely due to its actions on both dopamine and non-dopamine neurotransmission. Clinical studies of quetiapine have shown benefit for the treatment of alcohol and cocaine use disorders. Conceptually, the clinically prominent effects of quetiapine, namely sedation, anxiolysis, mood stabilization and appetite stimulation, are a good match for the symptoms of marijuana withdrawal. Most importantly, an open-label dose-finding study of quetiapine for the treatment of marijuana dependence conducted by our research group determined that quetiapine was well-tolerated and associated with reductions in marijuana use indicating that it is a promising agent deserving of further study in marijuana-dependent outpatients. The proposed research project is a randomized double-blind placebo-controlled clinical trial to evaluate the efficacy of quetiapine for the treatment of marijuana dependence over a 12-week period. All participants will receive Medical Management, a medication adherence focused psychosocial intervention that facilitates compliance with study medication and other study procedures, promotes abstinence from marijuana and other substances, and encourages mutual-support group attendance. All participants will receive voucher incentives for compliance with study visit attendance, returning study medication bottles, and completing other study procedures, with the objective of achieving a highly compliant sample. The goal of this phase II clinical trial is to build on our promising open-label pilot study results and examine th efficacy of quetiapine on participants' marijuana consumption under placebo-controlled double-blind conditions using an abstinence-initiation model, where participants will be using marijuana regularly at study entry, reduce their use, and then achieve abstinence. The specific aims of the projects are to determine whether quetiapine is superior to placebo in 1) reducing marijuana use and 2) achieving abstinence.