Does marijuana use cause the use of other drugs?

ADEVELOPMENTAL SEQUENCE OF INVOLVEMENT IN drugs is one of the best replicated findings in the epidemiology of drug use. Regular sequences and stages of progression in which the use of alcohol and cigarettes precedes the use of marijuana (cannabis), and, in turn, the use of marijuana precedes the use of other illicit drugs, has been observed in the United States as well as in other western societies. Very few individuals who have tried cocaine and heroin have not already used marijuana; the majorityhavepreviouslyusedalcoholor tobacco. Suchbehavioral regularities are subsumed under the “gateway hypothesis. ” The gateway hypothesis implies 3 interrelated propositions about sequencing, association of initiation, and causation. Sequencing implies that there is a fixed relationship between 2 substances, such that one substance is regularly initiated before the other. Association implies that initiation of one substance increases the likelihood of initiation of the second substance. Causation implies that use of the first substance actually causes use of the second substance. Causation, a controversial proposition, is the one most widely invoked in policy debates and is the proposition addressed in the article by Lynskey et al in this issue of THE JOURNAL. Several strategies are available for determining the causal role of a lower-stage drug in the sequence on initiation of a higher-stage drug. In one strategy, epidemiologists attempt to specify the role of prior drug use on the subsequent use of other drug classes by controlling for theoretically relevant covariates and other confounding factors. Analyses based on this approach find that marijuana retains a significant association with the subsequent use of other illicit drugs even after control for risk and protective factors. However, in naturalistic population studies, it is not possible to control for all potential relevant factors. Morral et al have attempted to overcome this limitation by developing a simulation model, which assumes that the use of marijuana and other illicit drugs is explained solely by a general propensity to use drugs and the ages at first opportunity to use and at first actual use of marijuana and other illicit drugs. This common-factor model replicates the empirical association between marijuana and other illicit drugs observed in a national sample without positing an effect of the use of marijuana itself. However, the fit of this model was not compared with one in which the causal effect of marijuana use on initiation of use of other illicit drugs would also explicitly be taken into account. The argument would be stronger if the 2 models had been tested and the common-factor model was found to provide as good a fit as the causal model. While the simulation model of Morral et al does not disprove the existence of a causal relationship between marijuana and other illicit drugs, it provides an alternative interpretation. A second strategy is to evaluate the impact of prevention or intervention programs implemented among youths to prevent or reduce drug use. Such programs provide an imperfect substitution for an unrealizable social experiment in which adolescents would be randomly assigned to initiate the use of different drugs. However, programs designed to prevent or stop use of lower-stage drugs also seem to stop or reduce use of higher-stage drugs, as reported in Kandel. Still a third strategy is the use of genetically informative samples. This approach has not previously been implemented to test the gateway hypothesis and represents a unique contribution of the work of Lynskey et al. In a previous report based on data from a large sample of Australian twins born in 1964 to 1971, Lynskey et al concluded that genetic risk factors are important determinants of the risk of marijuana dependence, at least among men. In the current report, based on a subsample of 311 same-sex twin pairs from the Australian cohort who were discordant for early marijuana use by age 17 years, Lynskey et al find that early marijuana use by itself, even after control for other covariates, increases significantly the use of other illicit drugs. As the authors emphasize, the strength of the twin design is that twins are assumed to share the same environment and family experiences, and monozygotic pairs share the same genetic risk. If these factors explained the association between early marijuana use and the use of other illicit drugs, the risk of using these drugs would be the same for early marijuana-using twins and their discordant co-twins. But it is not. Thus, Lynskey at al conclude that “The results . were consistent with early cannabis use having a causal role as a risk factor for other drug use and for any drug abuse or dependence. ” But is the assumption of common environmental influences among twins too strong? An argument can be made that even identical twins do not share the same environment during adolescence and that envi-