A Mendelian randomization study using data from over 85,000 individuals found ADHD genetically causes an 8-fold increased risk of lifetime cannabis use, with 29% genetic correlation between the two conditions.
Psychiatrists treating ADHD, addiction geneticists, and ADHD medication prescribers.
ADHD causes 8-fold cannabis use risk (Mendelian randomization, N=85,623)
What the researchers found
Using GWAS data from 53,293 ADHD and 32,330 cannabis use subjects, genetic correlation between ADHD and lifetime cannabis use was r2=0.29 (p=1.63×10-5). Four new genome-wide significant loci were identified in cross-trait analysis. Mendelian randomization provided evidence that ADHD is causal for cannabis use (OR=7.9 for cannabis use in ADHD vs non-ADHD, 95% CI 3.72-15.51, p=5.88×10-5). The reverse direction was not supported.
Why it matters
Published in Molecular Psychiatry, this provides the strongest evidence yet that ADHD drives cannabis use, not the reverse. This has implications for treatment: addressing ADHD symptoms may be the most effective cannabis prevention strategy in this population.
The numbers in context
N=85,623; genetic correlation r2=0.29; ADHD→cannabis OR=7.9 (CI 3.72-15.51); 4 new genome-wide significant loci; 2 from single variant analysis, 2 from gene-based analysis.
How the study worked
Genome-wide association study meta-analyses with LD score regression for genetic correlation, cross-trait association analysis for shared loci, and two-sample Mendelian randomization for causal inference using summary statistics.
What this study cannot tell us
Mendelian randomization assumes genetic instruments are valid (pleiotropic effects possible); lifetime cannabis use is a binary measure (does not capture dose or problematic use); European ancestry GWAS data limits generalizability; ADHD phenotype in GWAS may not represent clinical ADHD.
How to read the evidence
Strong: Mendelian randomization in Molecular Psychiatry with large GWAS samples and multiple analytical approaches.
When this study was published
Published 2020.
The bigger picture
The 8-fold genetic risk from ADHD to cannabis use is substantial. If ADHD is a causal driver of cannabis use, then the high rates of cannabis use in ADHD populations are not a separate problem to manage but a downstream consequence of untreated or undertreated ADHD.
Questions still open
- Would effective ADHD treatment in childhood prevent cannabis use in adolescence? Are specific ADHD subtypes (inattentive vs hyperactive) differentially associated with cannabis use?
Common questions
Does ADHD cause cannabis use?
What does 29% genetic correlation mean?
Read the original research
Attention-deficit/hyperactivity disorder and lifetime cannabis use: genetic overlap and causality.
Molecular psychiatry, 25(10), 2493-2503
Citation
Soler Artigas, María; Sánchez-Mora, Cristina; Rovira, Paula; Richarte, Vanesa; Garcia-Martínez, Iris; Pagerols, Mireia; Demontis, Ditte; Stringer, Sven; Vink, Jacqueline M; Børglum, Anders D; Neale, Benjamin M; Franke, Barbara; Faraone, Stephen V; Casas, Miguel; Ramos-Quiroga, Josep Antoni; Ribasés, Marta. (2020). Attention-deficit/hyperactivity disorder and lifetime cannabis use: genetic overlap and causality.. Molecular psychiatry, 25(10), 2493-2503. https://doi.org/10.1038/s41380-018-0339-3
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