Genetic analysis found cannabis use disorder can causally increase risk of developing other substance use disorders | Research

The takeaway

Using Mendelian randomization and genomic analysis, researchers found that cannabis use disorder has causal genetic effects on opioid use disorder, problematic alcohol use, nicotine dependence, and smoking initiation, with bidirectional effects for most substances.

Genetics and addiction researchers; policy analysts assessing cannabis legalization effects on other substance use.

CUD genetically increases opioid use disorder risk (beta 0.93)

What the researchers found

CUD showed significant causal effects on all analyzed substance use traits: opioid use disorder (IVW beta 0.925), problematic alcohol use (0.443), smoking initiation (0.405), drinks per week (0.182), nicotine dependence (0.183), and cigarettes per day (0.150). Bidirectional effects were found, with OUD, PAU, smoking initiation, and DPW also increasing CUD risk. Importantly, CUD and simple cannabis use loaded onto different genetic factors, indicating they are genetically distinct.

Why it matters

This is among the strongest evidence that the genetic predisposition to cannabis use disorder directly increases risk for other addictions. The finding that CUD and cannabis use are genetically distinct means that casual use and problematic use have different biological underpinnings.

The numbers in context

CUD causal effect on OUD: IVW beta 0.925 (+/- 0.082). On problematic alcohol use: 0.443 (+/- 0.030). On smoking initiation: 0.405 (+/- 0.042). Bidirectional effects confirmed for OUD, PAU, smoking initiation, smoking cessation, and drinks per week.

How the study worked

Genetically informed analyses including local and global genetic correlations, genomic structural equation modeling (genomicSEM), and Mendelian Randomization (MR) using the latest CUD genomics data for unprecedented power.

What this study cannot tell us

Mendelian randomization assumes genetic instruments are valid; pleiotropy could confound results. European-ancestry-dominant samples limit generalizability. Genetic effects may interact with environmental factors not captured. Statistical causality does not perfectly map to clinical causality.

How to read the evidence

Advanced genomic methods (MR, genomicSEM) with unprecedented power provide strong genetic causal evidence, though genetic causality has caveats.

When this study was published

2024 study

The bigger picture

If CUD genetically increases risk for other addictions, cannabis legalization policies may need to account for downstream effects on opioid, alcohol, and tobacco use at the population level, beyond just cannabis-specific harms.

Questions still open

Could early treatment of CUD prevent development of other substance use disorders? Are the shared genetic factors treatable targets?

Common questions

What is Mendelian randomization?

A statistical method that uses genetic variants as natural experiments to estimate causal relationships. Because genes are assigned at conception, they are not affected by lifestyle factors, allowing researchers to separate cause from correlation.

Does this mean cannabis is a gateway drug?

The study shows shared genetic liability and causal genetic pathways between CUD and other substance disorders, which is more nuanced than the "gateway" concept. CUD (not just cannabis use) genetically increases risk, and the effects are bidirectional, with other substance disorders also increasing CUD risk.

Read the original research

Genetic influences and causal pathways shared between cannabis use disorder and other substance use traits.

Molecular psychiatry, 29(9), 2905-2910

View on PubMed ↗Publisher’s paper ↗

Citation

Galimberti, Marco; Levey, Daniel F; Deak, Joseph D; Zhou, Hang; Stein, Murray B; Gelernter, Joel. (2024). Genetic influences and causal pathways shared between cannabis use disorder and other substance use traits.. Molecular psychiatry, 29(9), 2905-2910. https://doi.org/10.1038/s41380-024-02548-y