# Identifying blood-based DNA methylation biomarkers of cannabis use

> **NIH NIH R01** · RESEARCH TRIANGLE INSTITUTE · 2022 · $523,313

## Abstract

PROJECT SUMMARY/ABSTRACT
The proposed study will accelerate the discovery of blood-based DNA methylation (DNAm) biomarkers for
cannabis use phenotypes (lifetime [ever vs. never] use and recency and frequency of use), by leveraging
existing data on 9,878 individuals across eight cohorts. Cannabis is the most commonly used illicit drug in
the United States, with 45% of Americans reporting lifetime use and 15% reporting past-year use in 2017.
Both adverse (e.g., cannabis use disorder, cognitive impairment, bronchitis, psychosis) and beneficial (e.g.,
therapeutic benefits for certain clinical conditions) effects have been reported. To understand the full
spectrum of associated health effects, there is an urgent need to develop tools that can accurately quantify
patterns of cannabis use across a lifetime, yet currently available biomarkers, with limited windows of
detection, lack these attributes. DNAm is an excellent candidate for biomarker development, as it has the
potential to differentiate acute from chronic exposure and timing, duration, and frequency of exposure. As
stressed by the National Institute on Drug Abuse director, Dr. Nora Volkow, and colleagues, there is an
“urgent need for biomarkers that reflect chronic drug exposure ...”; yet, biomarker research that “take[s]
advantage of epigenomics and epitranscriptomics is in its infancy”.
 We propose to assemble a collection of existing datasets across eight cohorts, enabling the largest
epigenome-wide association study (EWAS) analyses of any cannabis use phenotype to date (N = 9,878). In
Aim 1, we will identify general DNAm biomarkers of lifetime cannabis use (i.e., observed DNAm differences
that can be driven by genetics and/or exposure). To achieve Aim 1, we will conduct an EWAS meta-analysis
of lifetime cannabis use, from which we will use penalized regression to train and validate multi-CpG
predictive models (i.e., DNAm biomarkers). In Aim 2, we will identify genetically- vs exposure-driven
biomarkers of lifetime cannabis use, independently of Aim 1, by taking a multi-stage approach to tease apart
the underlying mechanisms driving the DNAm differences. Each type of biomarker can be uniquely
informative, with general biomarkers possibly providing the greatest overall predictive ability, genetically
driven biomarkers as a refined phenotype for genetic studies, and exposure-driven biomarkers for evaluating
the possible impact of behavior modification on related health effects. In Aim 3, we will develop general
DNAm biomarkers of persistent (i.e., DNAm changes detected in both recent and former users), transient
(i.e., DNAm changes detected in only recent users), and heaviness of cannabis use effects. These
biomarkers can enable more specific future evaluations of cannabis-related outcomes (e.g., adverse effects
related to persistent DNAm changes) and potential treatment applications (e.g., to help monitor adherence,
as informed by a combination of transient and persistent DNAm changes).

## Key facts

- **NIH application ID:** 10452701
- **Project number:** 5R01DA048824-03
- **Recipient organization:** RESEARCH TRIANGLE INSTITUTE
- **Principal Investigator:** Fang Fang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $523,313
- **Award type:** 5
- **Project period:** 2020-09-30 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10452701

## Citation

> US National Institutes of Health, RePORTER application 10452701, Identifying blood-based DNA methylation biomarkers of cannabis use (5R01DA048824-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10452701. Licensed CC0.

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