Evaluating the drug use “gateway” theory using cross-national data: Consistency and associations of the order of initiation of drug use among participants in the WHO World Mental Health Surveys

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Abstract

Background

It is unclear whether the normative sequence of drug use initiation, beginning with tobacco and alcohol, progressing to cannabis and then other illicit drugs, is due to causal effects of specific earlier drug use promoting progression, or to influences of other variables such as drug availability and attitudes. One way to investigate this is to see whether risk of later drug use in the sequence, conditional on use of drugs earlier in the sequence, changes according to time-space variation in use prevalence. We compared patterns and order of initiation of alcohol, tobacco, cannabis, and other illicit drug use across 17 countries with a wide range of drug use prevalence.

Method

Analyses used data from World Health Organization (WHO) World Mental Health (WMH) Surveys, a series of parallel community epidemiological surveys using the same instruments and field procedures carried out in 17 countries throughout the world.

Results

Initiation of “gateway” substances (i.e. alcohol, tobacco and cannabis) was differentially associated with subsequent onset of other illicit drug use based on background prevalence of gateway substance use. Cross-country differences in substance use prevalence also corresponded to differences in the likelihood of individuals reporting a non-normative sequence of substance initiation.

Conclusion

These results suggest the “gateway” pattern at least partially reflects unmeasured common causes rather than causal effects of specific drugs on subsequent use of others. This implies that successful efforts to prevent use of specific “gateway” drugs may not in themselves lead to major reductions in the use of later drugs.

Introduction

Community epidemiological research, concentrated in North America and Oceania, has documented a common sequence of drug use initiation that begins with tobacco and alcohol use, followed by cannabis and then other illicit drugs. This pattern was originally described as the “gateway pattern”, with use of an earlier drug in this sequence predicting progression to use of later ones (e.g. cannabis and other drugs) (Grau et al., 2007, Kandel et al., 1986, Kandel et al., 1992, Kandel and Faust, 1975, Kandel, 1984, van Ours, 2003, Yamaguchi and Kandel, 1984).

Some commentators have argued that the gateway pattern is due to a causal effect of earlier substance use on use of later substances (Fergusson et al., 2006, Rebellon and Van Gundy, 2006). A variety of pathways have been proposed, some more reductionist than others. One suggestion for a gateway effect of cannabis use on subsequent opioid use, for example, is that cannabis alters the opioid system in the brain, leading to a change in hedonic processing that promotes subsequent opioid use (Ellgren et al., 2007). If true, such causal effects of earlier substances in the gateway sequence on subsequent use of later substances would suggest that efforts to prevent use of specific earlier drugs might help reduce initiation of the later ones. However, the gateway pattern observed in epidemiological data is also consistent with the existence of one or more unmeasured common causes, such as a risk-taking predisposition and latent propensity to use drugs as just one of a range of risk behaviours, rather than a causal effect of earlier gateway drugs (Morral et al., 2002). If common causes account for the gateway pattern, then we would not expect prevention of use of specific earlier drugs in the sequence to cause a reduction in use of later substances. Debate about these possibilities continues (Fergusson et al., 2006, Hall, 2006, Morral et al., 2002, Schenk, 2002).

One approach to investigating this issue that has not been pursued in the past is to examine data on time-space variation in use of drugs earlier and later in the gateway sequence. An analogous approach was presented by Weiss et al. (1988) in their evaluation of cocaine use among hospitalised drug users: cocaine use was strongly related to mood disorder in cohorts studied in 1980–1982, but when cocaine use was more common (1982–1986) the association between mood disorder and cocaine was reduced. Similarly, the association between nicotine dependence and psychiatric disorders has become stronger in more recent US cohorts as smoking has become less common; a pattern that is thought to be related to changes in social norms, such that nicotine dependence is a more powerful marker of “deviance” now than when smoking was much more normative in the past (Breslau et al., 2004). These studies suggest that the association between cocaine and tobacco use and mood disorders may not be a simple causal one; and perhaps that the prevalence of drug use might impact upon associations with other variables. Conversely, if associations between the use of a drug and other outcomes (such as psychiatric disorders or other drug use) were causal, we would expect changes in prevalence of one drug to have no impact on associations with later outcomes (e.g. cannabis use would remain similarly associated with other illicit drug use, but there would be lower levels of those later outcomes).

The Weiss et al. analysis is compelling: it could be taken to suggest that the pharmacological effects of cocaine were less important in predicting adverse outcomes than sociocultural meanings of use (i.e. a shift from being a rarely used drug, perhaps perceived as dangerous, with those using it high risk-takers; to later use by a considerably larger proportion of the population). This implies that some external (sociocultural) factors influenced changes in prevalence of use, with the difference in prevalence due to reasons that would not be expected to influence the outcomes under study (other than through exposure to cocaine).

This assumption is formalised in the econometric method of instrumental variables analysis, in which a causal determinant of a putative risk factor is found, which can be assumed not to have any direct causal effect on an outcome other than through the risk factor (Pearl, 2000). When such an instrument is found, it can be used to estimate the magnitude of the causal effect of the risk factor on the outcome in such a way as to separate out any bias due to reciprocal causation or unmeasured common causes. The classic case in economics was the use of information about forest fires in Northwest USA, and railroad strikes, to influence the price of lumber, which in turn influenced the number of new housing starts. This allowed the effects of economic stimulation on interest rates to be estimated, independent of the effects of the interest rate on economic stimulation (Angrist & Krueger, 2001).

Assuming that time-space variation in the prevalence of drug use results at least in part from instrumental variables, we can study the extent to which variation in use of early “gateway” drugs predicts subsequent change in use of later drugs in the gateway sequence. We know, for example, that US tobacco use dropped dramatically in the 1990s, due to a combination of public education campaigns and aggressive taxation policy, influences that would not be expected to have any direct effect on use of cannabis or other illicit drugs other than through the effect of reducing tobacco use. Was this reduction in tobacco use accompanied by the reduction in use of illicit drugs that would be predicted by the gateway theory? We are unaware of any direct analysis of epidemiological data aimed at answering that question.

We present this type of analysis here. Rather than focus on a single country in a single time period though, we present cross-national comparisons, combining information about between-country differences with information about within-country through-time variation, to examine broad patterns of association. No attempt is made to measure explicit instrumental variables. Instead, we work on the implicit assumption that the time-space variation in prevalence of earlier so-called gateway drugs (alcohol, tobacco and cannabis) reflects factors that would not be expected to influence use of later drugs directly. This makes the comparison of time-space variation useful for making preliminary inferences about the potential effects of interventions to specifically reduce use of drugs early in the “gateway” sequence upon use of drugs later in the sequence.

Cross-national data can provide some information on this issue, as the prevalence of licit and illicit drug use varies dramatically across countries and cultures. If the “gateway sequence” was consistent across diverse countries, this would provide support for a more strongly causal interpretation of the sequence. Alternatively, if there was variation in both levels and associations across countries, this would support the putative influence of other variables on the association. Some limited data exist on this issue. Specifically, two studies in New Zealand (Wells and McGee, 2008) and the United States (Degenhardt et al., 2009) found that violations of the normative order of substance initiation, although uncommon, were more common among more recent cohorts, who also had a higher prevalence of drug use. They also found that “violating” this sequence was not associated with increased dependence risk. Rather, it was prior cumulative exposure to total drugs, and an earlier onset of initiation, that were significant predictors of transition to dependence. These results argue against the hypothesis that use of specific “gateway” drugs has a causal effect on subsequent initiation of use of later ones.

It would be useful to extend these results to a larger set of countries with a wider range of variation in drug use to consider the consistency of the order of initiation of drug use, and observe whether associations between use of one drug and initiation of another are consistently observed. The current paper presents the results of such an extension using the World Health Organization (WHO) World Mental Health (WMH) Surveys, a series of parallel community epidemiological surveys using the same instruments and field procedures that were carried out in 17 countries throughout the world. The aims of this study are to

  • (1)

    examine the prevalence of drug use by age 29 years across age cohort and country;

  • (2)

    consider if differences in prevalence are associated with differences in associations with drug use later in the “gateway” sequence;

  • (3)

    examine whether violations of the “gateway” sequence vary according to age cohort and country differences in prevalence of drug use earlier in the sequence;

  • (4)

    examine whether the specific order of initiation of drug use predicts later development of drug dependence.

Section snippets

Sample

WMH surveys were carried out in 7 countries classified by the World Bank (World Bank, 2003) as developing (Colombia, Lebanon, Mexico, Nigeria, Peoples’ Republic of China, South Africa, Ukraine) and 10 classified as developed (Belgium, France, Germany, Italy, Japan, Israel, Netherlands, New Zealand, Spain, and United States of America). The total sample size was 85,088, with individual country sample sizes ranging from 2372 (the Netherlands) to 12,992 (New Zealand). The weighted average response

Cross-national and cohort differences in drug use

Drug use by age 29 years by age group at interview is presented in Table 2 for all 17 countries. South Africa had the lowest level of alcohol use, with 40.6% of the total sample reporting any use by age 29 years, followed by Lebanon (52.8%), Nigeria (55.6%) and Israel (55.7%). Tobacco use was relatively rare in South Africa (32.4%) and Nigeria (16.1%). Cannabis use was very low in Nigeria (2.8%), Japan (1.6%), and the People's Republic of China (0.3%). Despite relatively low rates of alcohol

Discussion

The present paper examined the extent and ordering of licit and illicit drug use across 17 disparate countries worldwide. This comparison, using surveys conducted with representative samples of the general population in these countries, and assessment involving comparable instruments, allowed for the first assessment of the extent to which initiation of drug use follows a consistent pattern across countries. Previous studies, concentrated in high income countries with relatively high levels of

Role of funding sources

The surveys discussed in this article were carried out in conjunction with the World Health Organization World Mental Health (WMH) Survey Initiative. We thank the WMH staff for assistance with instrumentation, fieldwork, and data analysis. These activities were supported by the United States National Institute of Mental Health (R01MH070884), the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the US Public Health Service (R13-MH066849, R01-MH069864, and R01 DA016558), the

Contributors

Lisa Dierker, Louisa Degenhardt, Maria Elena Medina-Mora, Yehuda Neumark, Nancy Sampson, and Ronald Kessler contributed to the conception, design and interpretation of analysis for this manuscript. Lisa Dierker, Wai Tat Chiu, Nancy Sampson, and Ronald Kessler contributed to the analysis of the manuscript. Drafting of the manuscript was done by Lisa Dierker, Louisa Degenhardt, Maria Elena Medina-Mora, Yehuda Neumark, Nancy Sampson, and Ronald Kessler. All the other authors contributed to the

Conflict of interest statements

Dr. Degenhardt was provided by Reckitt Benckiser with an untied educational grant to monitor the extent of injection of buprenorphine–naloxone injection, following its introduction in Australia, and compared with methadone and buprenorphine. The design, conduct, reporting and interpretation of the results of the study were determined by the study investigators. Dr. Kessler has been a consultant for GlaxoSmithKline Inc., Kaiser Permanente, Pfizer Inc., Sanofi-Aventis, Shire Pharmaceuticals, and

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