How your first reactions to tobacco and cannabis predict later dependence risk | Research

The takeaway

Initial subjective reactions to tobacco were associated with onset of both nicotine dependence and cannabis abuse/dependence, while initial reactions to cannabis predicted only cannabis-related diagnoses.

Read this if you are curious about why first experiences with drugs differ between people and what those differences predict about future risk.

27-35% of variation in initial drug reactions was heritable

What the researchers found

In a study of female twins, researchers examined how initial reactions to tobacco and cannabis (the first time each was used) related to later development of DSM-IV diagnoses. Positive and negative reaction factors emerged for both substances.

Initial reactions to tobacco predicted the onset of both nicotine dependence and cannabis abuse/dependence, suggesting that first tobacco experiences may serve as a broader indicator of substance vulnerability. Initial reactions to cannabis, however, were associated only with cannabis-specific diagnoses.

Genetic factors accounted for 27-35% of the variation in initial reactions to both substances. The overlap between reaction factors was partly attributable to shared genetic influences and partly to shared individual-specific environmental factors.

Why it matters

Understanding why some people progress from first use to dependence while others do not is central to addiction research. This study showed that measurable differences in how individuals respond to their very first drug experience are partially genetically influenced and predictive of later clinical outcomes.

The numbers in context

2,393 twins with tobacco use history and 1,445 with cannabis use history were analyzed. Heritability of initial reaction factors: 27-35%. Genetic correlations between positive and negative reaction factors across substances ranged from 0.18 to 0.58.

How the study worked

Factor analysis and Cox proportional hazards modeling in a population-based sample of Caucasian female twins aged 18-32 years. Tobacco analyses included 2,393 individuals with lifetime tobacco use; cannabis analyses included 1,445 with lifetime cannabis use. Classical twin modeling estimated genetic and environmental contributions to initial reactions and their covariation.

What this study cannot tell us

The sample included only Caucasian female twins, limiting generalizability to males and other populations. Retrospective recall of initial reactions may be influenced by subsequent use patterns. The study could not determine which specific genetic variants underlie the heritable component.

How to read the evidence

Well-powered twin study with appropriate statistical methodology, though limited to female twins and retrospective recall.

When this study was published

Published in 2014.

The bigger picture

The finding that initial tobacco reactions predicted cannabis outcomes, but not vice versa, supports the concept of a common vulnerability to substance use disorders that may manifest first through tobacco (which is typically tried earlier). This does not necessarily support a "gateway" theory but rather a shared genetic susceptibility model.

Questions still open

Would the same patterns appear in males? Do initial reactions to cannabis predict other substance use disorders in mixed-sex samples? Could measuring initial drug reactions help identify individuals at elevated risk for dependence?

Common questions

Does how you react the first time you use a drug predict addiction?

This study found that initial reactions to tobacco predicted the onset of both nicotine dependence and cannabis abuse/dependence. Initial cannabis reactions predicted cannabis diagnoses specifically. These initial reactions were partly genetically influenced (27-35% heritable).

Is there a genetic link between tobacco and cannabis responses?

Yes. Genetic factors partly explained the overlap between initial reactions to tobacco and cannabis, with genetic correlations between reaction factors ranging from 0.18 to 0.58, suggesting shared genetic vulnerability.

Read the original research

Initial reactions to tobacco and cannabis smoking: a twin study.

Addiction (Abingdon, England), 109(4), 663-71

View on PubMed ↗Publisher’s paper ↗

Citation

Agrawal, Arpana; Madden, Pamela A F; Bucholz, Kathleen K; Heath, Andrew C; Lynskey, Michael T. (2014). Initial reactions to tobacco and cannabis smoking: a twin study.. Addiction (Abingdon, England), 109(4), 663-71. https://doi.org/10.1111/add.12449