England UK

From ukcia-mh

Correspondence

Does cannabis use cause schizophrenia?

John Macleoda, , George Davey Smithb and Matthew Hickmanb

aDepartment of Primary Care and General Practice, Primary Care Clinical
Sciences and Learning Centre Building, University of Birmingham,
Birmingham B15 2TT, UK bDepartment of Social Medicine, University of
Bristol, Bristol, UK

As Wayne Hall notes in his Comment (Jan 21, p 193),1 we have been more
cautious than others about the strength of epidemiological evidence that
cannabis use causes schizophrenia.2 We think this caution is well founded.
The importance of considering residual confounding, bias, and reverse
causation as alternative explanations for small increased relative risks
apparent in methodologically heterogeneous observational studies not
amenable to informative meta-analysis is a hard lesson epidemiologists
have learned from experience.3

We are also cautious about reports of genetically based vulnerability of
some individuals to a psychotogenic effect of cannabis use.4 No robust
main effect of COMT genotype was seen in this study, effects being
confined to the subgroup of cannabis users who started use in adolescence.
Time will tell, and we agree further study of this question is important,
but such interaction-only effects confined to subgroups rarely replicate.5
Further, even if an effect of cannabis is confined to the genetically
vulnerable, the average increased risk apparent in non-genetically
informed studies is around two-fold overall. Given the (often small)
cannabis doses that this risk was associated with, generally over fairly
short follow-up periods, it is noteworthy that a substantial increase in
schizophrenia has not been seen after apparently substantial increases in
population cannabis exposure.

None of this evidence excludes the possibility of a causal effect.
Population changes in other factors causing schizophrenia might have
masked effects of cannabis and, in any case, data on population rates of
both cannabis use and schizophrenia are neither abundant nor of high
quality. In individuals, non-causal artifact is likely to explain part of
the apparent association, but not necessarily all of it.

It is also unfortunate that the debate around whether cannabis causes
schizophrenia has become conflated with the debate around the legal status
of cannabis, and that this question has come to dominate discussions
around the appropriate public-health response. The public-health case for
prevention of cannabis use by young people is strong, irrespective of
whether use also causes schizophrenia. Most users seem to smoke cannabis
with tobacco; cannabis use can actually lead to initiation of tobacco use,
reinforce toxic effects of tobacco, and make abstinence from tobacco more
difficult. Moreover, in most jurisdictions, cannabis use exposes young
people to risks of criminalisation that could have additional adverse
consequences for their health. We need to develop (because they do not
currently exist) cost-effective and humane interventions to reduce
cannabis use by young people. Assessment of the effects of these
interventions should also allow clarification of the true consequences of
cannabis use.2

Schizophrenia is enormously important; it remains substantially
unexplained and thus unpreventable. If up to 50% (as the most extreme
estimates suggest) of schizophrenia is genuinely attributable to cannabis
use, this provides considerable scope for prevention. However, premature
conclusions around causality are likely to be counterproductive and could
hinder the overall endeavour to find ways to effectively improve
population mental health.

We declare that we have no conflict of interest.


References
1 W Hall, Is cannabis use psychotogenic?, Lancet 367 (2006), pp.
193–195.

2 J Macleod, R Oakes and A Copello et al., The psychological and social
sequelae of use of cannabis and other illicit drugs by young people:
systematic review of longitudinal, general population studies, Lancet 363
(2004), pp. 1579–1588.

3 G Davey Smith and S Ebrahim, Data dredging bias or confounding, BMJ 325
(2002), pp. 1437–1438.

4 A Caspi, TE Moffitt and M Cannon et al., Moderation of the effect of
adolescent-onset cannabis use on adult psychosis by a functional
polymorphism in the catechol-O-methyltransferase gene: longitudinal
evidence of a gene X environment interaction, Biol Psychiatry 57 (2005),
pp. 1117–1127.

5 HM Colhoun, PM McKeigue and G Davey Smith, Problems of reporting genetic
associations with complex outcomes, Lancet 361 (2003), pp. 865–872.


--
Phil Stovell, South Hampshire, UK

"They said I should not take him to the police, but rather
let him pay a dowry for my goat because he used it as his wife"