Study: CBC and CBD Combo Shrinks Drug-Resistant Triple-Negative Breast Cancer Tumors in Lab and Animal Models

A new peer-reviewed study published in Drug Delivery and Translational Research by researchers from Florida A&M University reports that combining the non-intoxicating cannabinoids cannabichromene (CBC) and cannabidiol (CBD) produced strong anti-tumor effects against a form of triple-negative breast cancer (TNBC) that had become resistant to the chemotherapy drug doxorubicin. TNBC is considered one of the most aggressive forms of breast cancer and is particularly difficult to treat once resistance to standard chemotherapy develops. With limited treatment options available for patients in this situation, the research team investigated whether a combination of CBC and CBD could slow tumor growth and overcome this resistance.

Using doxorubicin-resistant MDA-MB-231 TNBC cells, researchers conducted both two-dimensional and three-dimensional lab assays to measure cell death and tumor behavior. Combination index analysis confirmed the two cannabinoids worked synergistically rather than independently. The treatment caused cancer cells to become arrested in the G0/G1 phase of the cell cycle and reduced the cells’ ability to invade surrounding tissue by about 55% in a Matrigel invasion test.

The study then moved into animal testing. In xenograft models using BALB/c nude mice implanted with doxorubicin-resistant tumors, mice were treated with CBC at 10 milligrams per kilogram, CBD at 20 milligrams per kilogram, or the combination of both. The combined treatment reduced tumor volume roughly twice as much as either cannabinoid alone and four times more than the untreated control group.

Molecular analysis provided insight into why the treatment was effective. Western blot testing showed that the combination therapy suppressed several key cancer-promoting pathways, including MEK/ERK and PI3K/AKT/mTOR signaling. Proteins involved in cell cycle progression and survival—Cyclin D1, CDK6, SOD2, and NF-κB—were also significantly reduced.

The researchers also examined how the cannabinoids behaved in the body. Pharmacokinetic studies in rats, supported by GastroPlus simulations, showed that taking CBC and CBD together increased peak concentration (Cmax) and overall exposure (AUC) without delaying absorption time. Modeling suggested the improvement was due to enhanced absorption in the jejunum, indicating the cannabinoids may help improve each other’s bioavailability when used together.

According to the researchers, this is the first study to evaluate the combined effects of CBC and CBD against doxorubicin-resistant TNBC using lab, animal, and pharmacokinetic models together. The findings suggest that pairing these cannabinoids may offer a new strategy for addressing chemotherapy resistance in one of the most difficult forms of breast cancer.