Pharmacological Treatment of Marijuana Dependence

描述（由申请人提供）： 据估计，4.2%的美国人口依赖大麻。在那些寻求 在接受大麻治疗后，只有一小部分人能够戒烟。在我们之前的资助期间，我们开发了一个实验室模型，确定了减轻大麻戒断症状的药物。这种竞争性延续的目的是改进我们的模型，以预测减少大麻使用复发的药物，定义为在一段时间的禁欲后恢复吸食大麻。这个建议的基本假设是：1）依赖和戒断在维持频繁使用大麻中起作用，2）减弱大麻戒断或大麻的积极强化作用将减少复发。目标1。建立大麻复吸的实验室模型。我们假设，禁欲将：（1）增加戒断症状，（2）减少自我管理大麻的潜伏期，（3）增加自我管理大麻的数量。 目标2。评估药物干预减少大麻复吸的能力， 减轻大麻戒断症状使用这个模型，我们将评估口腔THC， 奈法唑酮，我们已经证明它可以减少大麻戒断症状。我们假设口服THC和奈法唑酮将：（1）剂量依赖性地增加自我施用大麻的潜伏期，和（2）因此，剂量依赖性地减少大麻戒断一段时间后自我施用的大麻量。目标3。评估药物干预的能力，以减少大麻的直接影响，以减少大麻的使用。我们将评估大麻素受体拮抗剂SR141716A。我们假设，SR将剂量依赖性地减少大麻禁欲一段时间后自我管理的大麻的数量。对于导致大麻治疗寻求者高复发率的因素知之甚少。该方案的优势在于我们利用受控实验室环境来检查药物对大麻自我给药的相互作用，在模型复发的条件下。收集的数据将提供有关维持几乎每天使用大麻的积极和消极强化因素的信息，并将提出更有效的治疗大麻依赖的方法。

DESCRIPTION (provided by applicant): It is estimated that 4.2% of the U.S. population is dependent on marijuana. Among those seeking treatment for their marijuana use, only a small percentage are able to achieve abstinence. During our previous funding period, we developed a laboratory model that identified medications that attenuate symptoms of marijuana withdrawal. The objective of this competing continuation is to refine our model to predict medications that decrease relapse to marijuana use, defined as the resumption of marijuana smoking after a period of abstinence. The underlying assumption of this proposal is that 1) dependence and withdrawal play a role in maintaining frequent marijuana use, and 2) attenuating either marijuana withdrawal or marijuana's positive reinforcing effects will decrease relapse. Aim #1. Develop a laboratory model of marijuana relapse. We hypothesize that abstinence will: (1) increase symptoms of withdrawal, (2) decrease the latency to self-administer marijuana, (3) increase the quantity of marijuana self-administered. Aim #2. Evaluate the ability of pharmacological interventions to decrease marijuana relapse by attenuating symptoms of marijuana withdrawal. Using this model, we will evaluate oral THC and nefazodone, which we have shown decrease symptoms of marijuana withdrawal. We hypothesize that both oral THC and nefazodone will: (1) dose-dependently increase the latency to self-administer marijuana, and (2) thus, dose-dependently decrease the quantity of marijuana self-administered following a period of marijuana abstinence. Aim #3. Evaluate the ability of pharmacological interventions to decrease marijuana use by attenuating marijuana's direct effects. We will evaluate the cannabinoid receptor antagonist, SR141716A. We hypothesize that SR will dose-dependently decrease the quantity of marijuana self-administered following a period of marijuana abstinence. Little is known about the factors contributing to the high relapse rates in marijuana treatment-seekers. The strength of this protocol lies in our utilization of a controlled laboratory setting to examine the interactive effects of medications on marijuana self-administration under conditions that model relapse. The data collected will provide information on the positive and negative reinforcing factors maintaining near-daily marijuana use, and will suggest more efficacious approaches to treating marijuana dependence.