Genetic Variants Influence Endocannabinoid System Gene Expression Differently Across Body Tissues | Research

The takeaway

Analysis of over 30,000 individuals found that genetic variants significantly influence endocannabinoid system gene expression in tissue-specific patterns, with the female reproductive system showing fewer genetic effects.

genetics researchers, pharmacogenomics specialists, reproductive medicine researchers, cannabinoid therapy developers

What the researchers found

In 31,684 participants from eQTLGen, 22,020 genetic variants (eQTLs) influenced 43 of 70 selected ECS genes. Across 49 tissues in GTEx, 69 of 70 ECS genes had tissue-specific genetic effects. The female reproductive system had fewer eQTLs compared to other physiological systems. In the endometrium specifically, FABP3 (an endocannabinoid transporter) showed significant genetic effects, with 13 additional ECS genes showing FDR-significant eQTLs.

Why it matters

Individual genetic differences in the endocannabinoid system may explain why people respond differently to cannabis. Understanding tissue-specific genetic effects is essential for developing targeted cannabinoid-based therapies.

The numbers in context

31,684 participants (eQTLGen); 838 donors, 49 tissues (GTEx); 206 endometrial samples. 22,020 eQTLs for 43/70 ECS genes. 69/70 genes had tissue-specific eQTLs. FABP3 significant in endometrium. 14 independent FDR-significant eQTLs for 13 ECS genes in endometrium.

How the study worked

Analysis of publicly available genomic datasets: eQTLGen (31,684 participants, blood-based), GTEx (838 donors, 49 tissues), and an in-house endometrial dataset (206 samples). Examined genetic variant effects on expression of 70 endocannabinoid system genes.

What this study cannot tell us

Datasets are from European-ancestry-predominant populations. Gene expression does not necessarily reflect protein levels or receptor function. Endometrial samples are a small dataset. Cannot directly predict clinical cannabinoid response from eQTL data.

How to read the evidence

Large well-powered genomic datasets with rigorous statistical methods, but functional implications of eQTLs for clinical cannabinoid response remain to be established.

When this study was published

2025 publication.

The bigger picture

This research explains a fundamental challenge in cannabinoid medicine: the same dose of cannabis or cannabinoid medication may have vastly different effects in different people because their genetic makeup influences how their endocannabinoid system functions in specific tissues.

Questions still open

Could genetic testing predict individual response to cannabinoid therapies?
Why does the female reproductive system have fewer ECS genetic effects?

Common questions

Why do people respond differently to cannabis?

This study found over 22,000 genetic variants that influence how endocannabinoid system genes are expressed, and these effects differ across body tissues. This means your genetic makeup partly determines how your body responds to cannabinoids in different organs.

Could genetics predict how someone responds to medical cannabis?

This study identified tissue-specific genetic effects on endocannabinoid system genes, which is a first step. However, translating these genomic findings into clinical predictions for individual cannabinoid response requires further research.

Read the original research

The influence of genetics on the endocannabinoid system gene expression and relevance for targeting reproductive conditions.

Journal of cannabis research, 7(1), 29

View on PubMed ↗Publisher’s paper ↗

Citation

Tanaka, Keisuke; Amoako, Akwasi A; Mortlock, Sally; Rogers, Peter A W; Holdsworth-Carson, Sarah J; Donoghue, Jacqueline F; Teh, Wan Tinn; Montgomery, Grant W; McKinnon, Brett. (2025). The influence of genetics on the endocannabinoid system gene expression and relevance for targeting reproductive conditions.. Journal of cannabis research, 7(1), 29. https://doi.org/10.1186/s42238-025-00275-x