Non-medical painkiller misuse shares moderate genetic overlap with cannabis use but not cannabis use disorder | Research

The takeaway

A twin study found non-medical analgesic use is 46% heritable and shares moderate genetic overlap with cannabis use (r=0.41) and nicotine use (r=0.45), but minimal genetic overlap with cannabis use disorder (r=0.15).

People interested in genetics of addiction, the gateway drug debate, and why some substance users develop disorders while others don't.

Genetic overlap: cannabis use rg=0.41 vs cannabis use disorder rg=0.15

What the researchers found

NMUA heritability was 46%. Genetic correlations were moderate with cannabis use (rg=0.41), nicotine use (rg=0.45), and nicotine dependence (rg=0.34), but weak with cannabis use disorder (rg=0.15) and alcohol use disorder (rg=0.07). This suggests the genetics of trying substances overlaps, but the genetics of developing disorders is largely distinct.

Why it matters

The distinction between genetics of substance use versus substance use disorder is crucial. The same genes that increase likelihood of trying substances don't necessarily increase the risk of becoming dependent, suggesting different biological mechanisms for initiation versus addiction.

The numbers in context

2,007 twins, 66% female, mean age 25.9. NMUA lifetime prevalence: 19.4%. Heritability: 46% (95% CI: 0.29-0.57). Genetic correlations: cannabis use rg=0.41, nicotine use rg=0.45, nicotine dependence rg=0.34, cannabis use disorder rg=0.15, alcohol use disorder rg=0.07.

How the study worked

Biometrical genetic analysis of 2,007 young adult twins (66% female, mean age 25.9) from the Brisbane Longitudinal Twin Study, using structural equation univariate and multivariate modeling to estimate heritability and genetic correlations between NMUA and other substance outcomes.

What this study cannot tell us

Australian twin sample may not generalize globally. Self-reported substance use. Predominantly female sample (66%). Cross-sectional retrospective assessment. NMUA category combines non-opioid and opioid analgesics.

How to read the evidence

Moderate: well-established twin methodology with appropriate sample size, but cross-sectional and single-country sample.

When this study was published

Published in 2019, using 2009-2016 data.

The bigger picture

This finding challenges the "gateway drug" concept at the genetic level. While there is shared genetic vulnerability to trying multiple substances, the genetic architecture of developing a disorder for each substance appears largely independent. General risk-taking genes may drive initiation, while disorder-specific genes drive dependence.

Questions still open

What specific genes contribute to the shared initiation vulnerability? Why is the genetic overlap with disorders so much weaker than with use? Could the shared genetics reflect a general risk-taking or sensation-seeking trait rather than substance-specific pathways?

Common questions

Is painkiller misuse genetically related to cannabis use?

Moderately. This twin study found a genetic correlation of 0.41 between non-medical analgesic use and cannabis use. However, the genetic overlap with cannabis use disorder was much weaker (0.15), suggesting different genes drive trying substances versus becoming dependent.

Does this support the gateway drug theory?

Partially. Shared genetics may explain why people who try one substance are more likely to try others. But the weak overlap with use disorders suggests that escalation to addiction involves different biological mechanisms than initial experimentation.

Read the original research

Genetic and environmental risk factors in the non-medical use of over-the-counter or prescribed analgesics, and their relationship to major classes of licit and illicit substance use and misuse in a population-based sample of young adult twins.

Addiction (Abingdon, England), 114(12), 2229-2240

View on PubMed ↗Publisher’s paper ↗

Citation

Gillespie, Nathan A; Bates, Timothy C; Hickie, Ian B; Medland, Sarah E; Verhulst, Brad; Kirkpatrick, Robert M; Kendler, Kenneth S; Martin, Nicholas G; Benotsch, Eric G. (2019). Genetic and environmental risk factors in the non-medical use of over-the-counter or prescribed analgesics, and their relationship to major classes of licit and illicit substance use and misuse in a population-based sample of young adult twins.. Addiction (Abingdon, England), 114(12), 2229-2240. https://doi.org/10.1111/add.14750