Combining the cannabinoid cannabinol (CBN) with the breast cancer drug exemestane may significantly improve treatment outcomes for patients with estrogen receptor-positive (ER+) breast cancer, according to a new study published in the European Journal of Pharmacology.
Researchers from Universidade do Porto in Portugal and the Technical University of Denmark evaluated the effects of CBN in combination with three aromatase inhibitors commonly used in clinical settings—anastrozole, letrozole, and exemestane. The experiments, conducted using MCF-7aro breast cancer cells and tumor spheroids, revealed that only the combination of CBN and exemestane produced a meaningful reduction in cancer cell viability and growth.
The study found that CBN enhanced the anti-tumor action of exemestane by reducing the expression of aromatase, the enzyme responsible for estrogen production. This combination also improved the regulation of estrogen receptor alpha (ERα) and androgen receptor (AR) activity—key targets in ER+ breast cancer therapy. Notably, the CBN and exemestane pairing helped overcome one of exemestane’s drawbacks—its weak estrogen-like effect—while also preventing AR overexpression, which can contribute to treatment resistance.
The researchers also compared the transcriptomic profiles of this combination with those of exemestane alone and exemestane plus cannabidiol (CBD), identifying distinct molecular pathways affected by each. These findings may help clarify how different cannabinoids function in cancer treatment and open the door to more effective combination therapies.
The authors conclude by saying “this study strengthens the hypothesis that cannabinoids are important anti-cancer agents with attractive co-adjuvant properties.”
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