What determines an individual's vulnerability to the harmful effects of cannabis?

A young person who has ever used cannabis has a 40% increased risk of developing a psychotic disorder like schizophrenia; in those using heavily, the increased risk can be 200%. There are also rapidly growing numbers of young people now seeking treatment for cannabis addiction. The Times recently headlined that in England: ?500 cannabis smokers a week seek medical help? (January 11th, 2008). Further, the effects of cannabis on the brain raise concerns that young people who use this drug may under-achieve in education or work. What we don?t yet understand is why some individuals can use cannabis with few apparent harmful effects whereas others become mentally ill or addicted or have problems concentrating and remembering.

In the first research of its kind, we recently discovered that two main constituents (THC and CBD) in the cannabis that young people smoke influence the psychotic-like effects they experience in everyday life. The proposed research builds on this finding and on our recent large-scale study with 244 young people assessing the effects of cannabis. It aims to determine which cannabis-related and which individual factors make some young people vulnerable to the harmful effects of the drug. The three main harms it addresses are psychotic-like symptoms, addiction and cognitive impairment. The first phase of the study will be naturalistic and involve 600 16-23 year olds who differ in their cannabis use. Some cannabis users will be selected for Phase 2 - a controlled, laboratory study of the effects of two main constituents of cannabis (THC and CBD) both alone and combined. In both Phases, the effects we will assess are psychotic-like, addiction-related and cognitive. We will also investigate young people?s beliefs and views about different strains of cannabis, such as skunk and sinsemilla.

At the time of writing this proposal, the Government is waiting for findings of yet another review of the classification of cannabis. Whether or not this results in it being raised from Class C to B will have negligible impact on cannabis users.

If we show that the harmful effects can be reduced if vulnerable youngsters choose strains with higher CBD content, or if they take CBD supplements, then this could lead to a new era of safer cannabis use. Importantly, it could significantly reduce the numbers of young people in the UK currently diagnosed schizophrenic who would not have become mentally ill if they had not used this drug.

The current debate on the harmful effects of cannabis centres mainly on psychosis but increasingly on addiction and cognitive impairment. A major unanswered question is: why are some individuals vulnerable and others resilient to these harmful effects? Our very recent finding suggests that one major constituent of cannabis ‘cannabidiol (CBD)‘ protects against the harmful effects of THC, the drug‘s main psychoactive constituent. The present research aims to determine how the CBD and THC content of cannabis interact with vulnerability factors - including an individual?s psychosis-proneness and level of cannabis use - to determine their acute response to this drug, a potential marker of longer-term harm. Phase I will be the first ever large-scale naturalistic study of the acute effects of cannabis and will involve 600 16-23 year olds: 200 daily and 200 recreational users, 100 ex-users and 100 non-using controls. Psychosis-like, dependence-related and cognitive effects will be assessed both whilst users are and are not intoxicated with the drug in a cross-over design. THC and CBD content of cannabis habitually taken will be measured in hair and that taken acutely will be measured in the ‘spliff‘ actually smoked as well as saliva/urine levels. Relevant genetic markers will be assessed. Individuals‘ beliefs about and preferences for different strains of cannabis (e.g. skunk, hash) and intake behaviours (e.g. titration of dose) will also be explored. Phase II will employ the same psychotic-like, dependence-related and cognitive measures in a double-blind, balanced, placebo-controlled comparison of the acute effects of pure CBD and THC, both alone and in combination, in 48 cannabis users carefully selected from Phase I to differ in psychosis-proneness (high versus low) and extent of use (daily versus recreational). An intermediate phase of the study involves a semi-structured interview with subsets of 20 daily, recreational and ex-users to allow detailed exploration of reasons for use, strains of cannabis used and response to information on risk factors (including personal feedback). If, as hypothesised, CBD protects against psychotic-like, cognitive and/or dependence-inducing effects of cannabis, this would have major implications for public health given that 40-50% of young British people use this drug. The potential use of CBD as a protective agent by vulnerable young people could significantly reduce the 14% who are currently diagnosed with a psychotic disorder in the UK who would not have been if they had not consumed cannabis. It could also impact clinically on prevention and treatment of cannabis dependence.