Improving Substance Use and Clinical Outcomes in Heavy Cannabis Users

描述（由申请人提供）：大麻是美国使用最多的非法物质。先前的研究表明，非典型抗精神病药物减少了有或没有精神疾病的受试者的物质使用频率和数量。到目前为止，还没有对照研究评估非典型抗精神病药物在减少大麻使用障碍患者使用大麻和其他物质方面的有效性。我们假设非典型抗精神病喹硫平是一种有效的药物，可以改善大麻使用障碍患者的物质使用结果。在这项试点研究中，我们将在重度大麻使用者（即大麻依赖者，每周吸烟三次或更多）中验证这一假设。因为这些重度大麻使用者中有50%的人在吸烟时报告有精神病经历（即减弱的阳性症状），并且有复发精神病症状的风险，我们将把这个试点临床试验的重点放在大麻使用者的这个亚组上，以增加本研究的风险/效益比，并瞄准可能从喹硫平的抗精神病作用中受益的人群。考虑到缺乏评估非典型抗精神病药物对重度大麻使用者疗效的对照研究，评估非典型抗精神病药物对该人群药物使用和临床结果的有效性对于改善这些个体的预后至关重要。因此，这项随机、双盲、安慰剂对照研究的目的是评估120名大麻依赖、最近（一年内）精神病症状减轻、每周使用大麻3次或以上的受试者的非典型抗精神病药（喹硫平）的疗效，以达到以下目的：(1)减少大麻和其他物质的使用；(2)防止精神病性经历的复发。我们还将评估喹硫平对渴望和情绪的影响，以及它的耐受性。该项目将是一项为期12周、随机、双盲、安慰剂对照的喹硫平研究，它将包括对症状、药物使用和副作用的全面评估。这项研究将通过提供非典型抗精神病药物治疗对易患精神病的重度大麻使用者的相对疗效和耐受性的独特数据，使该领域受益。这项研究将为未来评估非典型抗精神病药物对大麻使用障碍患者的长期疗效和耐受性的研究奠定基础。

DESCRIPTION (provided by applicant): Cannabis is the most used illicit substance in the United States. Previous studies suggest that atypical antipsychotics decrease the frequency and the amount of substance use in subjects with and without psychotic illness. So far, there are no controlled studies assessing the effectiveness of atypical antipsychotics for decreasing cannabis and other substance use in individuals with cannabis use disorders. We postulate that the atypical antipsychotic quetiapine is an effective agent for improving substance use outcomes in subjects with cannabis use disorders. In this pilot study, we will test this hypothesis in heavy cannabis users (i.e., individuals who are cannabis dependent and smoke three times or more per week). Because 50% of these heavy cannabis users report histories of psychotic experiences (i.e., attenuated positive symptoms) while smoking and are at risk for recurring psychotic symptoms, we will focus this pilot clinical trial on this subgroup of cannabis users in order to increase the risk/benefit ratio of this study and target a population that may also benefit from the antipsychotic effect of quetiapine. Considering the lack of controlled studies assessing the efficacy of atypical antipsychotics in heavy cannabis users, assessing the effectiveness of an atypical antipsychotic medication on substance use and clinical outcomes in this population is critical for improving the prognosis of these individuals. Thus, the aims of this randomized, double-blind, placebo-controlled study are to assess the efficacy of an atypical antipsychotic (quetiapine) in 120 subjects with cannabis dependence, a recent history (within a year) of attenuated psychotic symptoms, and using cannabis 3 times or more per week for: (1) decreasing the use of cannabis and other substances; and (2) preventing the recurrence of psychotic experiences. We will also assess the effects of quetiapine on craving and mood, and its tolerability. This project will be a 12-week, randomized, double-blind, placebo-controlled study with quetiapine and it will include a comprehensive assessment of symptoms, substance use, and side effects. This study will benefit the field by providing unique data on the relative efficacy and tolerability of treatment with atypical antipsychotics in heavy cannabis users with a vulnerability to psychosis. This study will be the basis for future studies assessing the long-term efficacy and tolerability of atypical antipsychotics in individuals with cannabis use disorders. PUBLIC HEALTH RELEVANCE: Cannabis is the most used illicit substance in the United States, and there are no recommended pharmacological intervention for decreasing substance use and improving clinical outcomes in subjects with cannabis dependence. Thus, this study could have high public health relevance if it demonstrates the efficacy of an atypical antipsychotic for improving the prognosis of these individuals.