We are unable to make any strong statements about mediation, as we did not test this formally, and in any case our data are observational. The association between the early-life factors we studied (measured prior to measurement of conduct problems) and adolescent cannabis use was attenuated on adjustment for conduct problem trajectory. Similarly, the association between conduct problem trajectory and subsequent cannabis use was attenuated on adjustment for early-life factors. In most instances this attenuation was not substantial and effects remained strong. This provides moderate evidence that while some of the effect of early-life adversity on subsequent risk of cannabis use could be mediated through conduct problems, an effect independent of this pathway also appears to be operating. Similarly, conduct problems appear to increase the risk of subsequent cannabis use irrespective of whether or not they are preceded by adversity in earlier life. Any causal inference based on these estimates is necessarily cautious, given the difficulty of identifying independent effects of closely correlated covariates and given plausible levels of measurement error and categorical outcome variables 36.
