Self reported use of cannabis in early adulthood was associated with an increased risk of developing schizophrenia. Risk increased in a dose dependent manner with increasing frequency of cannabis use, and this relation remained when analysis was restricted to subjects who had used only cannabis and no other drugs before conscription. The largest risk was seen in subjects reporting use of cannabis on more than 50 occasions. We found no association between cannabis and other psychotic illnesses, which implies that cannabis has a rather specific association with an increased risk of schizophrenia.
The association between use of cannabis and schizophrenia was stronger in subjects who were first admitted within five years of conscription. One explanation is that subjects with a prodrome of schizophrenia at conscription may have increased their cannabis use, perhaps as a means of self medication.2
But all subjects were screened at conscription, and we adjusted for other psychiatric problems recorded at that time. The relation with cannabis use was also observed in the later onset group, admitted more than five years after conscription. It seems more likely that the reduced association in the group with later onset is due to misclassification, as the number of people who discontinued cannabis use accumulated over time.22
Although adjustment for confounders substantially reduced the odds ratios, adjusting for poor social integration had only minimal effects. A similar effect was observed in the original study by Andreasson et al, who adjusted for the number of friends that the subjects reported having.4
We used a more comprehensive measure of social integration as it is likely that on its own this question was not a strong measure of sociable personality traits. Personality traits are difficult to measure accurately, however, and residual confounding remains a possibility. The association between cannabis and schizophrenia persisted even after adjusting for use of alcohol, cigarettes, and other drugs, all of which are likely to be indicative of risk taking behaviour. This implies that a shared risk factor (be it biological, genetic, or through personality traits) for developing schizophrenia and for using psychoactive substances does not adequately explain the association observed.
We are limited in that we have only data regarding use of cannabis before conscription. But if the pattern of increased initiation and reduced cessation of drug use seen in the schizophrenia group persisted after the time of conscription, this would result in us underestimating the effect size of cannabis. Fewer subjects in this cohort claimed to have used cannabis and other illicit drugs compared with similar cohorts that used anonymous questionnaires.23
The effect of under-reporting would again result in an underestimate of the true effect size. Non-response was similar for subjects developing schizophrenia and non-cases, although, as a further check, we repeated the analyses, having recoded non-responders as either users or non-users of cannabis. This made no difference when recoding was non-differential between cases and non-cases, but it increased the odds ratios substantially when recoding was differential.
It is possible that use of stimulants could explain the results if stimulants were able to induce a chronic psychotic illness, identical to schizophrenia. But we did not find an independent association between use of stimulants and schizophrenia, although power was reduced compared with other analyses. Although studies from the United States have found that initiation of amphetamine use peaks by age 18-20,22
it is possible that initiation of stimulants after conscription was more likely in subjects who had previously used only cannabis. But the absence of an independent association with use of stimulants in our data implies that cannabis is potentially the more important agent.
These findings are in keeping with accumulating evidence that cannabis has detrimental effects on mental health in some people.3
Molecular studies have shown that Δ9
-tetrahydrocannabinol, the active component of cannabis, increases release of dopamine in the mesolimbic pathway.24
Given the suggested relation between increased mesolimbic dopamine and positive symptoms of schizophrenia,25
such observations provide support for the hypothesis that cannabis may act as a risk factor for this disorder.
Use of cannabis use has increased substantially over the past few decades in the United Kingdom, and 50% of the population now report having used cannabis at least once.26
If cannabis increases the risk of schizophrenia by 30%, as implied by these results, then 13% of cases of schizophrenia could be prevented if cannabis use was eliminated from the population, assuming that a causal relation between cannabis use and schizophrenia really exists. The overall weight of evidence is that occasional use of cannabis has few harmful effects overall,2
and the drug is less likely to be used regularly and cause dependence than nicotine. Nevertheless, these results indicate a potentially serious risk to the mental health of people who use cannabis, particularly in the presence of other risk factors for schizophrenia. Such risks need to be considered in the current move to liberalise and possibly legalise the use of cannabis in the United Kingdom and other countries.