Cannabidiol: a novel treatment for cannabis dependence?

在欧洲，1%的成年人和近2%的14-17岁青少年对大麻上瘾。近年来，随着市场上可获得的大麻成分的变化(增加了具有高THC和缺乏CBD的臭鼬或辛西比拉)，大麻依赖率显着增加。在英国首次戒毒的客户中，大麻现在是28%接受戒毒治疗的人的主要成瘾，仅次于海洛因(41%)。目前，临床医生依赖于心理治疗，但效果非常有限。目前还没有针对大麻成瘾的药物治疗。如果我们找到一种安全、有效的药物，这可能会改善治疗，就像各种药物提高了戒烟率一样。它还将影响教育/职业成就和非法行为，并降低年轻人患与大麻有关的精神健康问题(如精神分裂症、抑郁症)的风险。临床前和人体研究表明，大麻二醇(CBD)是一种非常有前途的治疗方法，具有极好的耐受性和安全性。大麻戒断的关键后果之一是焦虑，而CBD可以降低焦虑。CBD已经显示出有希望的前认知和神经保护作用，可能会扭转与大麻依赖有关的一些认知缺陷。我们最近的研究表明，大麻依赖在使用“臭鼬”的人中更为常见。其他数据表明，CBD可能通过一种机制对大麻依赖具有保护作用。上瘾的一个关键特征是，吸毒者的注意力会被与滥用药物有关的线索强烈吸引，而不是其他线索，这使得戒毒变得困难。动物证据表明，CBD可以降低药物线索导致海洛因复发的能力。在依赖大麻的人中，我们发现CBD减少了对大麻相关图片的注意力吸引。在CBD之后，大麻使用者认为大麻图片不那么令人愉快。因此，CBD可能会降低药物线索的激励能力。总体而言，现在的证据表明，CBD通过针对依赖的关键机制以及同样重要的大麻戒断症状，是治疗大麻依赖的合理方法。该项目的目标是首先确定CBD的最佳剂量，然后评估其治疗大麻依赖的有效性。设计：参与者将是符合大麻依赖临床标准的16-26岁的人。第一阶段是一项剂量发现研究，将28天的治疗与CBD 200、400、800 mg或匹配的安慰剂进行比较。将在中期分析期间独立审查数据，以根据大麻使用和戒断症状的变化来确定最有效的剂量。第二阶段将扩大现有的小组人数，将新的参与者分配给MEDmg或安慰剂，直到每组有60人。第二阶段的成功标准包括CBD组比安慰剂组更多的戒断者或非依赖者，并且大麻戒断症状的强度显著降低。我们还预测，接受CBD治疗的患者将在记忆力、心理健康和工作/教育天数方面有所改善。应用：依赖大麻的人比依赖任何其他非法药物的人都多--全世界至少有1800万人。自2001年以来，对大麻治疗的需求增加了一倍多(毒品和犯罪问题办公室2010年世界毒品报告)。因此，有效的药物治疗将对身心健康大有裨益。它还将对大麻成瘾的相关心理和社会后果产生影响。此外，还可减少与大麻有关的急性危害(如焦虑、类似精神病的影响、增加道路交通事故的风险)。这项研究的成功将为大规模的临床试验提供非常强大的动力。

In Europe, 1% of all adults and nearly 2% of 14-17 year olds are addicted to cannabis. Rates of cannabis dependence have increased markedly over recent years alongside changes in the ingredients of cannabis available on the market (increasing skunk or sinsemilla with high THC and lacking CBD). Among UK first-time drug treatment clients, cannabis is now the primary addiction in 28% of those entering drug treatment, second only to heroin (41%). At present, clinicians rely on psychological treatments which have very limited effectiveness. There is no pharmacological treatment for cannabis addiction. If we found a safe, effective medicine this could improve treatment in a similar way that various medicines have improved rates of stopping tobacco use. It would also impact on educational/vocational achievement and illegal behaviour, and reduce young people's risks of cannabis-associated mental health problems (e.g. schizophrenia, depression). Converging preclinical and human research suggests cannabidiol (CBD) to be a highly promising treatment, with excellent tolerability and safety. One of the key consequences of cannabis withdrawal is anxiety and CBD reduces anxiety. CBD has shown promising pro-cognitive and neuroprotective effects which may reverse some of the cognitive deficits associated with cannabis dependence. Our recent research has shown that cannabis dependence is more common in those using 'skunk'. Other data suggest a mechanism by which CBD may be protective against cannabis dependence. A key feature of addiction is that an addict's attention is strongly drawn to cues related to the drug abused over and above other cues and this makes it hard to stop use. Animal evidence suggests that CBD can reduce the ability of drug cues to cause relapse to heroin. In people dependent on cannabis, we have found that CBD reduced attention grabbing by cannabis-related pictures. After CBD, cannabis users rated cannabis pictures as less pleasurable. Thus CBD may reduce the motivating power of drug cues. Overall, evidence now suggests that CBD is a logical treatment for cannabis dependence, by targeting key mechanisms both in dependence and equally importantly, cannabis withdrawal symptoms. This project's objectives are first to determine the optimal dose of CBD and then to evaluate its efficacy in treating cannabis dependence.Design: participants will be 16-26 year olds who meet clinical criteria for cannabis dependence. Stage 1 is a dose-finding study comparing 28 days' treatment with CBD 200, 400, 800mg or matched placebo. Data will be independently reviewed during interim analyses to identify the Most Effective Dose based on measures of changes in cannabis use and withdrawal symptoms. Stage 2 will then expand existing group numbers by allocating new participants to either MEDmg or placebo until there are 60 in each group. Success criteria at Stage 2 include more individuals in the CBD than the placebo group being abstinent or non-dependent and significantly reduced intensity of cannabis withdrawal symptoms. We also predict that those given CBD treatment will show improvements in memory, psychological well-being and days in work/education. Application: More people are dependent on cannabis than any other illicit drug - at least 18 million worldwide. The demand for cannabis treatment has more than doubled since 2001 (UNODC World Drug Report 2010). An effective pharmacological treatment would therefore be a major benefit to mental and physical health. It would also impact upon associated psychological and social consequences of cannabis addiction. Benefits would additionally accrue in a reduction of the acute harms associated with cannabis (e.g. anxiety, psychosis-like effects, increased risk of road traffic accidents). The success of this study would provide a very strong impetus for a large scale clinical trial.