Reducing the harmful effects of cannabis use: finding the optimal CBD:THC ratio

据估计，全球有1.82亿人使用大麻。有迹象表明，这一数字正在上升，估计有30%的英国公众尝试过。高效大麻占主导地位，其主要活性化合物δ -9-四氢大麻酚（THC）含量很高，而保护性化合物大麻二酚（CBD）含量很少或根本没有。对普通人群的大量研究一致表明，使用大麻的人更有可能在以后的生活中患上精神病。精神病患者会出现令人不快的症状，如妄想和幻觉，这些症状很难治疗，可能持续数年甚至一生。重要的是，比较不同类型的大麻的研究发现，与较弱的大麻相比，较强的大麻对精神病的风险更大。对健康志愿者的实验表明，这可能是由于高水平的四氢大麻酚和低水平的CBD。四氢大麻酚可以引起短暂的焦虑和精神病症状，而CBD可以帮助治疗患有焦虑或精神病的人。因此，含有更多CBD的大麻可能危害更小。然而，之前的大多数研究都无法将四氢大麻酚和CBD的影响分开。此外，目前还不清楚究竟需要多少CBD来减少四氢大麻酚的有害影响。回答这个问题可以让大麻使用者降低患精神疾病、成瘾和记忆问题等心理健康问题的风险。在这项研究中，我们的目标是探索在45名志愿者中需要多少CBD来抵消四氢大麻酚的有害影响。在参加之前，将对参与者进行评估，以确保他们的身体和心理健康。然后，他们将被邀请进行4次单独的研究访问，每次访问间隔至少2周，在此期间，他们将被吸入4种不同效力的大麻蒸汽。标准化大麻材料将由荷兰Bredrocan BV公司（http://www.bedrocan.nl/）提供，吸入装置将由德国Storz & Bickel GmbH公司（http://www.storz-bickel.com/shop_eu/en/）提供。在每次研究访问中，参与者将以随机顺序获得CBD:THC比例为0:1、1:1、2:1和3:1的汽化大麻。参与者和研究人员都不知道在给定的研究访问中使用的是哪种CBD:THC比例。在吸入大麻蒸汽后，参与者将完成一系列测试，检查他们的认知功能，比如记住一串单词。然后，参与者将从国王医院的研究设施走一小段路到医院食堂——此前发现，在四氢大麻酚的影响下，这段路会增加焦虑和偏执。最后，参与者将填写与他们的情绪状态有关的问卷，一位训练有素的采访者将进行简短的临床访谈，以查看参与者是否经历过任何精神病症状。一整天，参与者将提供三份血液样本，用于分析CBD和四氢大麻酚的水平。我们预计CBD:THC的比例越大，参与者的认知、偏执和精神影响就越不明显。我们还预测，高剂量的CBD不会影响吸入大麻的愉悦效果，CBD也不会影响到达血液的四氢大麻酚的量。

Cannabis is used by an estimated 182 million people globally. There are indications that this number is on the rise and an estimated 30% of the UK public have tried it. There is a dominance of high-potency cannabis, high in its main active compound delta-9-tetrahydrocannabinol (THC) and with little or none of the protective compound cannabidiol (CBD). Large studies of the general population consistently show that people who use cannabis are more likely to develop psychosis later in life. People with psychosis experience unpleasant symptoms such as delusions and hallucinations, which are difficult to treat and can persist for years or even a whole lifetime. Importantly, studies comparing different types of cannabis have found that stronger cannabis poses an even greater risk to psychosis compared to weaker types. Experiments in healthy volunteers suggest that this might be due to both high levels of THC and low levels of CBD. THC can cause short-lived anxiety and psychotic symptoms, whereas CBD has can help to treat people suffering from anxiety or psychosis. It is therefore likely that cannabis with greater CBD would be less harmful. However, most previous studies have not been able to separate the effects of THC from CBD. Furthermore, it is unclear exactly how much CBD is needed to reduce the harmful effects of THC. Answering this question could allow cannabis users to reduce their risk of developing mental health problems like psychosis, addiction and memory problems. In this study we aim to explore how much CBD is needed to offset the harmful effects of THC in 45 volunteers. Participants will be assessed to make sure they are physically and psychologically healthy before taking part. They will then be invited for 4 separate study visits, each separated by a minimum of 2 weeks, in which they will be administered inhaled cannabis vapour of 4 different potencies. The standardised cannabis material will be provided by Bredrocan BV, Holland (http://www.bedrocan.nl/), and the inhalation device will be provided by Storz & Bickel GmbH, Germany (http://www.storz-bickel.com/shop_eu/en/). On each study visit, participants will be given vaporised cannabis with a CBD:THC ratio of 0:1, 1:1, 2:1 and 3:1 in a random order. Both the participants and researchers will be unaware of which CBD:THC ratio is being administered on a given study visit. Following the inhalation of cannabis vapour, the participants will complete a series of tests examining their cognitive functioning, such as remembering a list of words. The participant will then take a short walk from the research facility at King's Hospital to the hospital canteen - this has previously been found to increase anxiety and paranoia while under the influence of THC. Lastly, the participants will fill out questionnaires relating to their mood states and a trained interviewer will perform a short clinical interview to see if the participant has experienced any psychotic symptoms. Throughout the day, participants will provide 3 blood samples, which will be analysed for levels of CBD and THC. We expect that the greater the CBD:THC ratio is - the less pronounced the cognitive, paranoid and psychotic effects will be for the participants. We also predict that higher doses of CBD will not influence the pleasurable effects of the inhaled cannabis, nor will CBD influence the amount of THC which reaches the blood.