Non-medical painkiller misuse shares moderate genetic overlap with cannabis use but not cannabis use disorder
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).
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- Genetic overlap: cannabis use rg=0.41 vs cannabis use disorder rg=0.15
- Evidence Grade:
- Moderate: well-established twin methodology with appropriate sample size, but cross-sectional and single-country sample.
- Study Age:
- Published in 2019, using 2009-2016 data.
- Original Title:
- 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.
- Published In:
- Addiction (Abingdon, England), 114(12), 2229-2240 (2019)
- Authors:
- Gillespie, Nathan A(7), Bates, Timothy C, Hickie, Ian B(6), Medland, Sarah E, Verhulst, Brad, Kirkpatrick, Robert M, Kendler, Kenneth S, Martin, Nicholas G, Benotsch, Eric G
- Database ID:
- RTHC-02045
Evidence Hierarchy
A snapshot of a population at one point in time.
What do these levels mean? →Frequently Asked 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.
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Cite This Study
https://rethinkthc.com/research/RTHC-02045APA
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
MLA
Gillespie, Nathan A, et al. "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, 2019. https://doi.org/10.1111/add.14750
RethinkTHC
RethinkTHC Research Database. "Genetic and environmental risk factors in the non-medical us..." RTHC-02045. Retrieved from https://rethinkthc.com/research/gillespie-2019-genetic-and-environmental-risk
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.