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

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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.