A recent study published in the European Journal of Pharmacology offers compelling new evidence that cannabinol (CBN), a minor cannabinoid found in the cannabis plant, may significantly enhance the effectiveness of exemestane, a common aromatase inhibitor used to treat estrogen receptor-positive (ER+) breast cancer. These findings could open the door to new adjunctive therapies using cannabinoids in cancer care.
What Is Estrogen Receptor-Positive (ER+) Breast Cancer?
ER+ breast cancer is the most frequently diagnosed subtype of breast cancer. These tumors grow in response to estrogen, a hormone that is produced in the body, particularly after menopause through a process called aromatization. Aromatase inhibitors (AIs) such as anastrozole, letrozole, and exemestane block this process, helping to reduce tumor growth.
While AIs are a cornerstone of treatment, resistance to these therapies is a growing challenge. Many patients experience limited long-term benefits due to cancer cells adapting or finding alternative pathways for growth. This has led researchers to explore complementary therapies that could enhance efficacy or overcome resistance.
The Promise of Cannabinoids in Cancer Therapy
Cannabinoids have long been used in cancer care to manage side effects such as nausea and pain. But a growing body of research shows they may also have direct anti-tumor effects. Cannabinoids like THC and CBD have been shown to inhibit cancer cell proliferation, induce apoptosis (cell death), and interfere with angiogenesis (formation of new blood vessels that supply tumors).
This study, however, shifts the spotlight to a lesser-known compound: cannabinol (CBN). Unlike THC, CBN is non-intoxicating. Previous research had hinted that CBN might impact hormone-related pathways in breast cancer cells, but this is the first comprehensive look at its potential synergy with AIs, particularly exemestane.
Study Overview: CBN + Exemestane = Better Outcomes
Researchers from the University of Porto and the Technical University of Denmark evaluated the effects of combining CBN with each of the three major aromatase inhibitors—anastrozole,letrozole, and exemestane—on ER+ breast cancer cells and 3D spheroids (a lab model that mimics tumor structure more closely than 2D cell cultures).
The results were clear: CBN significantly enhanced the anti-cancer effects of exemestane but not the other AIs.
Key findings included:
- Synergistic Effect: The combination of CBN and exemestane reduced cancer cell viability more effectively than either treatment alone.
- Apoptosis Activation: Increased markers of programmed cell death.
- Aromatase Regulation: CBN blocked the synthesis of aromatase enzymes that exemestane alone couldn’t suppress over time.
- Estrogen Receptor Modulation: CBN reduced ERα levels and countered exemestane’s weak estrogen-like effects.
- Androgen Receptor (AR) Impact: CBN reversed the AR-boosting side effect of exemestane.
How Does CBN Compare to CBD?
The researchers also compared CBN to cannabidiol (CBD), a more commonly studied cannabinoid. While both improved exemestane’s performance, CBN showed unique advantages:
- CBD was more effective at enhancing apoptosis.
- CBN suppressed aromatase gene expression and neutralized exemestane’s estrogen-like side
effects more effectively.
Gene expression analysis revealed that each cannabinoid affected different molecular pathways, suggesting that CBN and CBD may have distinct therapeutic roles.
Why This Matters for Breast Cancer Patients
Exemestane is often used when breast cancer becomes resistant to other AIs, but even this “last line” therapy has limitations. The addition of CBN may:
- Enhance cancer cell death
- Reduce the likelihood of exemestane resistance
- Improve hormone receptor modulation
- Provide a safe, plant-derived adjunctive therapy
Looking Ahead: What Needs to Happen Next?
Clinical trials are needed to confirm these promising results in humans. Future research should determine optimal dosing, safety profiles, and long-term effects.
Conclusion
This study supports a growing body of evidence that cannabinoids like CBN may play a direct role in cancer therapy. When paired with exemestane, CBN enhances its effectiveness while potentially reducing unwanted side effects. This promising combination warrants further clinical investigation.
Citation: Almeida CF, Valente MJ, Teixeira N, et al. Cannabinol improves exemestane efficacy in estrogen receptor-positive breast cancer models: a comparative study with cannabidiol. Eur J Pharmacol. 2025;1000:177712. doi:10.1016/j.ejphar.2025.177712 (Source: https://doi.org/10.1016/j.ejphar.2025.177712)
Dr. Ryan Zaklin is a board-certified Internal Medicine physician and a Harvard-trained expert in Integrative and Functional Medicine. He brings deep experience from his work at Massachusetts General Hospital and the Spaulding Rehabilitation Network. As founder of ECS Wellness, Dr. Zaklin leads the clinical strategy with a focus on the endocannabinoid system, mind-body medicine, and plant-based therapies. He regularly educates medical professionals and the public on cannabis therapeutics and continues to advance research and innovation in integrative care.
