Cannabidiol: a novel treatment for cannabis dependence?

大麻二酚：大麻依赖的新疗法？

• 批准号: MR/K015524/1
• 负责人: Helen Curran
• 金额: $ 142.15万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK015524%2F1
• 关键词: Cannabidiol; novel; treatment; cannabis; dependence

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.

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，随着市场上大麻成分的变化（高四氢大麻酚和缺乏CBD的臭鼬或辛半叶增加），大麻依赖率显着增加。在英国首次接受药物治疗的客户中，大麻是目前进入药物治疗的人中28%的主要成瘾者，仅次于海洛因（41%）。目前，临床医生依赖的心理治疗效果非常有限。大麻成瘾没有药物治疗方法。如果我们找到一种安全有效的药物，就能像各种药物提高戒烟率那样改善治疗。它还将对教育/职业成就和非法行为产生影响，并减少年轻人患与大麻有关的心理健康问题（如精神分裂症、抑郁症）的风险。临床前和人体研究表明，大麻二酚（CBD）是一种非常有前途的治疗方法，具有良好的耐受性和安全性。戒断大麻的主要后果之一是焦虑，而CBD可以减轻焦虑。CBD已经显示出有希望的促进认知和神经保护作用，这可能会逆转一些与大麻依赖相关的认知缺陷。我们最近的研究表明，大麻依赖在那些使用“臭鼬”的人身上更为常见。其他数据表明，CBD可能通过一种机制来防止对大麻的依赖。成瘾的一个关键特征是，成瘾者的注意力强烈地被与滥用药物有关的线索所吸引，而不是其他线索，这使得它很难停止使用。动物证据表明，CBD可以降低毒品线索导致海洛因复发的能力。在依赖大麻的人群中，我们发现CBD减少了与大麻有关的图片对注意力的吸引。服用CBD后，大麻使用者认为大麻图片的愉悦感降低了。因此，CBD可能会降低药物线索的激励能力。总的来说，现在的证据表明，CBD是一种合乎逻辑的大麻依赖治疗方法，针对的是依赖和同样重要的大麻戒断症状的关键机制。本项目的目标首先是确定CBD的最佳剂量，然后评估其治疗大麻依赖的功效。设计：参与者将是16-26岁，符合大麻依赖的临床标准。第一阶段是一项剂量发现研究，将28天的治疗与CBD 200,400,800mg或匹配的安慰剂进行比较。在中期分析期间，将对数据进行独立审查，以根据大麻使用变化和戒断症状的措施确定最有效剂量。第二阶段将扩大现有组的人数，将新参与者分配到MEDmg或安慰剂组，直到每组有60人。第2阶段的成功标准包括，与安慰剂组相比，CBD组中有更多的人戒断或不依赖大麻，并且大麻戒断症状的强度显著降低。我们还预测，那些接受CBD治疗的人在记忆力、心理健康和工作/教育时间方面都会有所改善。应用：依赖大麻的人比依赖其他任何非法药物的人都多——全世界至少有1800万人。自2001年以来，大麻治疗的需求增加了一倍以上（毒品和犯罪问题办公室《2010年世界毒品报告》）。因此，有效的药理学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，减少与大麻有关的急性危害（例如焦虑、类似精神病的影响、道路交通事故风险增加）也会带来益处。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。

项目成果

Salience attribution and its relationship to cannabis-induced psychotic symptoms.

• DOI: 10.1017/s0033291716002051
• 发表时间: 2016-12
• 期刊: PSYCHOLOGICAL MEDICINE
• 影响因子: 6.9
• 作者: Bloomfield, M. A. P.;Mouchlianitis, E.;Morgan, C. J. A.;Freeman, T. P.;Curran, H. V.;Roiser, J. P.;Howes, O. D.
• 通讯作者: Howes, O. D.

Cannabis potency: the need for global monitoring.

大麻效力：全球监测的必要性。

• DOI: 10.1111/add.13207
• 发表时间: 2016
• 期刊: Addiction (Abingdon, England)
• 作者: Freeman TP

Examining the profile of high-potency cannabis and its association with severity of cannabis dependence.

• DOI: 10.1017/s0033291715001178
• 发表时间: 2015-11
• 期刊: Psychological medicine
• 影响因子: 6.9
• 作者: Freeman TP;Winstock AR
• 通讯作者: Winstock AR

P.3.19 The effects of cannabidiol on cerebral blood flow and its relationship to memory: an arterial spin labelling study

P.3.19 大麻二酚对脑血流量的影响及其与记忆的关系：动脉自旋标记研究

• DOI: 10.1016/j.euroneuro.2019.01.081
• 发表时间: 2019
• 期刊: European Neuropsychopharmacology
• 影响因子: 5.6
• 作者: Green S