Mendelian randomization using genetic data from the largest available genome-wide studies found evidence for causal pathways from ADHD liability to smoking and cannabis initiation, but not convincingly in the reverse direction.
ADHD clinicians, addiction geneticists, substance use prevention researchers
Genetic evidence supports causal pathways from ADHD to cannabis and smoking initiation
What the researchers found
Genetic liability to ADHD increased the likelihood of smoking initiation, heavier smoking, difficulty quitting smoking, and cannabis initiation. There was weak evidence for ADHD increasing alcohol dependence risk. In the reverse direction, weak evidence for smoking initiation increasing ADHD risk was likely due to horizontal pleiotropy rather than true causation.
Why it matters
This genetic causal inference method avoids the confounding that plagues observational studies. Finding that ADHD liability causes increased substance use, rather than the reverse, has direct implications for prevention: treating ADHD may help prevent substance use.
The numbers in context
Causal pathways confirmed from ADHD to: smoking initiation, cigarettes per day, reduced smoking cessation, cannabis initiation; weak evidence for ADHD to alcohol dependence; weak but likely confounded evidence for smoking to ADHD; no causal pathways between ADHD and coffee consumption.
How the study worked
Bidirectional Mendelian randomization using summary-level data from the largest available genome-wide association studies on ADHD, smoking, alcohol, cannabis, and coffee, with inverse-variance weighted regression and five sensitivity analyses.
What this study cannot tell us
Mendelian randomization assumes genetic variants only affect the outcome through the exposure (no pleiotropy), which may not always hold; GWAS samples are predominantly European ancestry; cannot identify specific mechanisms linking ADHD to substance use.
How to read the evidence
Strong causal inference methodology using largest available GWAS data with multiple sensitivity analyses, limited by assumptions inherent to Mendelian randomization.
When this study was published
Published in 2021 using largest available GWAS data.
The bigger picture
If ADHD is a causal driver of substance use rather than a consequence, early identification and treatment of ADHD could serve as a primary prevention strategy for substance use disorders.
Questions still open
- Would early ADHD treatment reduce cannabis and smoking initiation rates? What mechanisms mediate the causal effect of ADHD on substance use?
Common questions
Does ADHD cause cannabis use?
What is Mendelian randomization?
Read the original research
Investigating causality between liability to ADHD and substance use, and liability to substance use and ADHD risk, using Mendelian randomization.
Addiction biology, 26(1), e12849
Citation
Treur, Jorien L; Demontis, Ditte; Smith, George Davey; Sallis, Hannah; Richardson, Tom G; Wiers, Reinout W; Børglum, Anders D; Verweij, Karin J H; Munafò, Marcus R. (2021). Investigating causality between liability to ADHD and substance use, and liability to substance use and ADHD risk, using Mendelian randomization.. Addiction biology, 26(1), e12849. https://doi.org/10.1111/adb.12849
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