Pharmacological Treatment of Marijuana Dependence

描述(由申请人提供)： 据估计，美国有4.2%的人口依赖大麻。在那些寻求 在对他们使用大麻的治疗中，只有一小部分人能够实现戒烟。在我们之前的资助期间，我们开发了一个实验室模型，用于识别减轻大麻戒断症状的药物。这一竞争继续进行的目的是完善我们的模型，以预测减少大麻复发的药物使用，即戒烟一段时间后恢复吸食大麻。这一建议的基本假设是：1)依赖和戒断在维持频繁使用大麻方面发挥作用，2)减弱大麻戒断或大麻的积极强化作用将减少复发。目的#1.建立大麻复发的实验室模型。我们假设戒断将：(1)增加戒断症状，(2)缩短自我给药的潜伏期，(3)增加自我给药的数量。 目的#2.评估药物干预通过以下方式减少大麻复发的能力 减轻大麻戒断症状。使用该模型，我们将评估口服THC和 奈法唑酮，我们已经显示出大麻戒断症状的减少。我们假设口服THC和奈法唑酮都将：(1)剂量依赖性地延长自我给药的潜伏期，(2)因此，在一段时间的大麻戒断后，剂量依赖性地减少自我给药的数量。目的#3.评估药物干预通过减弱大麻的直接影响来减少大麻使用的能力。我们将评估大麻素受体拮抗剂SR141716A。我们假设，在一段时间的大麻戒断后，SR将以剂量依赖的方式减少自我给药的大麻数量。人们对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的实验室环境，在模拟复发的条件下，检查药物对大麻自我给药的交互影响。收集的数据将提供关于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.