A Gene Variant Affecting Dopamine Breakdown Influenced THC Blood Levels in Pain Patients | Research

The takeaway

The COMT 680 T>C genetic variant significantly influenced THC plasma levels in chronic pain patients using medical cannabis, while BDNF levels correlated with cannabinoid concentrations.

Medical cannabis patients, prescribers interested in pharmacogenomics, and researchers studying individual variation in cannabis response.

COMT gene variant significantly affected THC plasma levels (p = 0.017)

What the researchers found

The COMT 680 T>C genetic variant significantly influenced plasma levels of THC (p = 0.017). Patients using inhaled cannabis had significantly different BDNF (p = 0.004) and IL-10 (p = 0.009) levels compared to those using cannabis decoction. Both BDNF and neurofilament light chain levels correlated with cannabinoid concentrations.

Why it matters

This study provides early evidence that genetic makeup can affect how the body processes medical cannabis. If certain gene variants predict higher or lower drug levels, this could eventually help personalize cannabis dosing for pain patients.

The numbers in context

N = 58 patients. COMT 680 T>C variant associated with THC levels (p = 0.017). IL-10 difference by route (p = 0.009). BDNF difference by route (p = 0.004). 47 decoction users, 11 inhaled cannabis users.

How the study worked

Observational study of 58 patients with neuropathic or chronic pain treated with medical cannabis (47 decoction, 11 inhaled; 30 high-THC, 28 reduced-THC/CBD). Cannabinoid plasma concentrations were measured by UHPLC-MS/MS. Genetic variants were assessed by real-time PCR. Inflammation biomarkers analyzed by ELISA and neuronal markers by Single Molecule Array.

What this study cannot tell us

Very small sample size (58 patients, only 11 inhaled). The imbalanced group sizes limit statistical power. Multiple biomarkers were tested without correction for multiple comparisons. This is a preliminary finding that requires replication in larger cohorts.

How to read the evidence

Small observational study with only 58 patients. Findings are hypothesis-generating and require replication in much larger cohorts.

When this study was published

Published in 2025.

The bigger picture

Pharmacogenomics is transforming how many drugs are prescribed, but cannabis has largely been left out of this movement. Studies like this begin to build the foundation for genetically informed cannabis dosing.

Questions still open

Should COMT genotyping be considered before prescribing medical cannabis? Do the observed biomarker changes have clinical significance for pain outcomes?

Common questions

What is COMT and why does it matter for cannabis?

COMT (catechol-O-methyltransferase) is an enzyme that breaks down dopamine and other catecholamines. Variants in this gene affect enzyme activity and appear to influence how the body processes THC, potentially affecting drug levels and effects.

What is BDNF?

Brain-derived neurotrophic factor is a protein that supports nerve cell survival and growth. Its levels correlated with cannabinoid concentrations in this study, suggesting cannabis may influence neuronal health markers.

Read the original research

COMT Genetic Variants and BDNF Level Associations with Cannabinoid Plasma Exposure: A Preliminary Study.

Journal of xenobiotics, 15(3)

View on PubMed ↗Publisher’s paper ↗

Citation

Manca, Alessandra; Valz, Cristina; Chiara, Francesco; Palermiti, Alice; Mula, Jacopo; Soloperto, Sara; Antonucci, Miriam; De Nicolò, Amedeo; Luxardo, Nicola; Imperiale, Daniele; Vischia, Flavio; De Cori, David; Cusato, Jessica; D'Avolio, Antonio. (2025). COMT Genetic Variants and BDNF Level Associations with Cannabinoid Plasma Exposure: A Preliminary Study.. Journal of xenobiotics, 15(3). https://doi.org/10.3390/jox15030066