One in four at risk of cannabis psychosis BY MARK HENDERSON, SCIENCE CORRESPONDENT ONE in four people carries genes that increases vulnerability to psychotic illnesses if he or she smokes cannabis as a teenager, scientists have found. A common genetic profile that makes cannabis five times more likely to trigger schizophrenia and similar disorders has been identified, increasing pressure on the Government to reverse the drug’s reclassification from Class B to Class C. The increased risk applies to people who inherit variants of a gene named COMT who also smoked cannabis as teenagers. About a quarter of the population have this genetic make-up, and up to 15 per cent of the group are likely to develop psychotic conditions if exposed to the drug early in life. Neither the drug nor the gene raises the risk of psychosis by itself. The study, led by Avshalom Caspi and Terrie Moffitt, of the Institute of Psychiatry at King’s College London, offers the best explanation yet for the way that cannabis has a devastating psychiatric impact on some users but leaves most unharmed. Scientists had suspected that genetic factors were responsible for this divide, but a gene had not been pinpointed. The findings, to be published in Biological Psychiatry, also reinforce a growing consensus that nature and nurture are not mutually exclusive forces but combine to affect behaviour and health. The King’s team has previously identified genes that raise the risk of depression or aggression, but only in conjunction with environmental influences. Mental health campaigners said that the results vindicated their concerns about the decision last year to downgrade cannabis to a Class C drug, which means that possession is no longer an arrestable offence. Marjorie Wallace, chief executive of the mental health charity Sane, said that it was becoming clear that cannabis placed millions Class C drug, which means that possession is no longer an arrestable offence. Marjorie Wallace, chief executive of the mental health charity Sane, said that it was becoming clear that cannabis placed millions of users at risk of lasting mental illness. About fifteen million Britons have tried cannabis, and between two million and five million are regular users, according to the Home Office British Crime Survey. The research suggests that a quarter could be at risk. The evidence will be considered by a review of the drug’s classification announced last month by the Home Secretary. It may be possible to develop a test for genetic susceptibility to cannabis. “If we were able genetically to identify the vulnerable individuals in advance, we would be able to save thousands of minds, if not lives,” Ms Wallace said. Dr Caspi, however, rejected the idea of screening based on the COMT gene. “Such a test would be wrong more often than it is right. Cannabis has many other adverse effects, especially on developing teenagers, on respiratory health and possibly on cognitive function. Effects may be pronounced among a genetically vulnerable group but that doesn’t mean we should encourage others not genetically vulnerable to use cannabis.” The King’s team tracked 803 men and women born in Dunedin, New Zealand, in 1972 and 1973, who were enrolled at birth in a research project. Each was interviewed at 13, 15 and 18 about cannabis use, tested to determine which type of COMT genes they had inherited, and followed up at 26 for signs of mental illness. COMT was chosen as it is known to play a part in the production of dopamine, a brainsignalling chemical that is abnormal in schizophrenia. It comes in two variants, known as valine or methionine, and every person has two copies, one from each parent. Among people with two methionine variants, the rate of psychotic illness was 3 per cent, the background rate for the general population, regardless of whether they had used cannabis as teenagers. Among those with two valine variants the rate was 3 per cent for non-users but 15 per cent for those who had smoked cannabis in their teens. Dr Caspi said research had shown that the valine gene variant and cannabis affect the brain’s dopamine system in similar fashion, suggesting that they deliver a “double dose” that can be damaging. The work needs to be replicated by others to confirm the findings, Dr Caspi said. It also is possible that the gene involved is not COMT but a neighbour. THE DRUG OF CHOICE FOR MILLIONS • Cannabis was reclassified from a Class B to a Class C drug in January 2004. Possession remains illegal, but is not an arrestable offence. The Home Secretary has asked for a review by November • The Home Office estimates that fifteen million people have tried cannabis, two million to five million are regular users and reclassification has saved 199,000 hours’ police work • Liberalisation campaigners argue that millions smoke the drug with fewer ill-effects than others suffer from alcohol or tobacco • A recent study at Maastricht University found that cannabis doubles the risk of schizophrenia, hallucinations and paranoia among a genetically susceptible group Should the Government rethink its drugs policy?