People with schizophrenia are twice as likely as people in the general population to smoke cannabis (van Os et al., 2002). This has prompted researchers to ask whether there is a causal link between cannabis abuse and the development of psychosis. A methodologically rigorous study of conscripts to the Swedish army shows that, compared to those who had never used cannabis, young men who were heavy cannabis users by the time they were 18 were more than six times more likely to have developed schizophrenia 27 years later (Zammit et al., 2002). This association also remained even after people who had used other kinds of drugs were removed from the statistical analysis.
Other studies have now replicated this link (Arsenault et al., 2002, 2004; Fergusson et al., 2003; van Os et al., 2002) and highlighted early cannabis use as being particularly problematic. For example, Arsenault et al. (2002) reported that 10.3 percent of those who used cannabis by age 15 were diagnosed with signs of schizophrenia by age 26, compared with only 3 percent of the controls who did not use cannabis. Taken together, the research findings suggest that using cannabis more than doubles a person’s risk of developing schizophrenia at a later stage of life. They also point to adolescence as being a critical developmental period with respect to schizophrenia.
A major methodological concern in studies of this kind is whether people who are in the early stages of developing psychosis are more likely to use cannabis. If this were the case, cannabis use would simply be a correlate of schizophrenia and not a cause. However, even after childhood psychotic symptoms are considered and accounted for statistically, cannabis use has still been found to be a predictor of later schizophrenia (Fergusson et al., 2003).
Of course, the vast majority of people who use cannabis do not develop schizophrenia. So can we predict who is at higher risk? Using a large population sample, Caspi and colleagues (2005) have reported that people who carry a particular form of the COMT gene (one or two copies of the valine or val allele) are at increased risk for developing psychotic symptoms (hallucinations or delusions) in adulthood if they used cannabis during adolescence. In contrast, using cannabis has no adverse influence on those who have a different form of the COMT gene (two copies of the methionine or met allele). This is an exciting finding because it illustrates the importance of gene × environment interactions in the development of schizophrenia (see Figure 13.12).
Why should the val allele of the COMT gene be a risk factor? We still do not know. However, the finding is provocative because the COMT gene (which you may recall is on chromo-some 22) codes for a protein that plays a role the breakdown of dopamine. One of the active ingredients of cannabis (called THC) is also thought to increase the synthesis of dopamine. We further know that cannabis makes symptoms worse in patients who already have schizophrenia (D’Souza et al., 2005). So again, we have evidence of the importance of dopamine in schizophrenia and of the problems associated with cannabis use, although how everything fits together remains to be discovered.
Finally, we note that new research is showing that cannabis may actually accelerate the progressive brain changes that seem to go along with schizophrenia. Rais and colleagues (2008) collected brain scan data from 51 patients with recent-onset schizophrenia and 31 healthy controls. Nineteen of the patients were using cannabis (but not other illicit drugs) and 32 patients were not. When MRI scans were conducted again 5 years later, the patients who had continued to use cannabis during this time showed more marked decreases in brain volume relative to the patients who did not use cannabis. The changes in gray matter (brain cell) volume in the healthy controls, cannabis-using patients, and patients who did not use cannabis over the 5-year period are shown in Figure 13.13. Although both groups of patients lost more brain tissue over time than the healthy controls did, loss of brain tissue was especially pronounced in the patients who used cannabis. The conclusion is obvious. If you have schizophrenia, cannabis is probably very bad for your brain.
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