Cannabis and mental health

In the 1990s the use of cannabis increased much among young people so that it is now becoming more common than tobacco smoking in some countries.^1–2 The ready availability of the drug, the increasing social disapproval of cigarette smoking, stern drink driving laws, and perceptions that cannabis is safe or less harmful than cigarettes or alcohol may explain these changes. The increase in use is of concern because cannabis may be a gateway to other drugs,³ and it may cause psychiatric illnesses. The link between cannabis and psychosis is well established, and recent studies have found a link between use of marijuana and depression.^4–7 Does cannabis cause these conditions, or do patients use cannabis to relieve their distress?

The explanation most accepted is that cannabis triggers the onset or relapse of schizophrenia in predisposed people and also exacerbates the symptoms generally.⁴,⁵ Establishing direction of causality is difficult and is most appropriately assessed in non-clinical samples, but a low incidence of the illness and the fact that most drug users take other drugs in addition to cannabis create methodological problems and explain the dearth of reliable evidence.

The study often quoted in support of the causal hypothesis examined the incidence of schizophrenia in more than 50 000 Swedish conscripts followed up for 15 years.⁸ It showed that use of marijuana during adolescence increased the risk of schizophrenia in a dose-response relation. Questions have, however, remained about the validity of the diagnosis, the possible causal role of other drugs, and prodromal symptoms of schizophrenia that might have led to the use of cannabis, rather than cannabis triggering the psychosis.⁴,⁵

A longer follow up and reanalysis of this cohort published in this issue (p 1199) confirms the earlier findings and clarifies that cannabis, and not other drugs, is associated with later schizophrenia and that this is not explained by prodromal symptoms.⁹ In a similar vein, a three year follow up of a Dutch cohort of 4045 people free of psychosis and 59 with a baseline diagnosis of psychotic disorder showed a strong association between use of cannabis and psychosis.¹⁰ Length of exposure to use of cannabis predicted the severity of the psychosis, which likewise was not explained by use of other drugs. Participants who showed psychotic symptoms at baseline and used cannabis had a worse outcome, which also implies an additive effect. In a New Zealand cohort, individuals who had used cannabis three times or more by age 15 or 18 were not more likely to have schizophreniform disorder at age 26 (p 1212), although they showed an increase in “schizophrenia symptoms” (but not schizophrenia).¹¹ The meaning of “schizophrenia symptoms” requires clarification to interpret these results.

The evidence in relation to depression is growing. A 15 year follow up of an adult community sample of 1920 participants in the United States showed that use of cannabis increased the risk of major depression at follow up fourfold.⁷ Use of cannabis was specifically associated with an increase in suicidal ideation and anhedonia. Similar findings in an Australian study reported in this issue (p 1195) show a dose-effect relation between the use of cannabis and anxiety or depression in a large cohort of 14-15 year olds followed for seven years.¹² This is reflected in higher rates of anxiety or depression according to the frequency with which cannabis was used. The link is stronger for young women than young men in this cohort, although sex differences have not been found in other studies.⁶,⁷ Baseline depression did not predict later marijuana use in either study and therefore does not support the self medication hypothesis. The study in the New Zealand cohort did not find an association between cannabis use at age 15 and depressive disorder at age 26. The authors found, however, that young people who had used cannabis three times or more by age 18 were more likely to have a depressive disorder at age 26, even after use of other drugs was controlled for.

Although the number of studies is small, these findings strengthen the argument that use of cannabis increases the risk of schizophrenia and depression, and they provide little support for the belief that the association between marijuana use and mental health problems is largely due to self medication. Whether the use of cannabis triggers the onset of schizophrenia or depression in otherwise vulnerable people or whether it actually causes these conditions in non-predisposed people is not yet resolved. Further, it cannot be assumed that mechanisms are the same for both conditions (cannabinoids have effects on a variety of neurotransmitter systems) or at different developmental stages. For example, although evidence shows that mental disorder leads to the use of cannabis among adolescents, the reverse seems true in early adulthood.¹³

The shown dose-response relation for both schizophrenia and depression highlights the importance of reducing the use of cannabis in people who use it. It was estimated that lack of exposure to cannabis would have reduced the incidence of psychosis requiring treatment by as much as 50% in the Dutch cohort,¹⁰ and is similarly reflected in the Swedish cohort, showing that the use of cannabis increased the risk of schizophrenia by 30%.⁹ This large effect is surprising and not yet reflected in an increased incidence of schizophrenia in the population. If true, the use of cannabis will contribute to more episodes or new cases of the illness—food for thought for both clinicians and legislators.

Papers pp 1195, 1199, 1212