“Cannabidiol (CBD) is a non-psychoactive phytocannabinoid that has been discussed for its safety and efficacy in cancer treatments. For this reason, we have inquired into its use on triple-negative human breast cancer. Analyzing the biological effects of CBD on MDA-MB-231, we have demonstrated that both CBD dosage and serum concentrations in the culture medium influence its outcomes; furthermore, light scattering studies demonstrated that serum impacts the CBD aggregation state by acting as a surfactant agent. Pharmacological studies on CBD in combination with chemotherapeutic agents reveal that CBD possesses a protective action against the cytotoxic effect exerted by cisplatin on MDA-MB-231 grown in standard conditions. Furthermore, in a low serum condition (0.5%), starting from a threshold concentration (5 µM), CBD forms aggregates, exerts cytostatic antiproliferative outcomes, and promotes cell cycle arrest activating autophagy. At doses above the threshold, CBD exerts a highly cytotoxic effect inducing bubbling cell death. Finally, IGF-1 and EGF antagonize the antiproliferative effect of CBD protecting cells from harmful consequences of CBD aggregates. In conclusion, CBD effect is strongly associated with the physical state and concentration that reaches the treated cells, parameters not taken into account in most of the research papers.”

https://pubmed.ncbi.nlm.nih.gov/35806150/

“Among the various biological properties of phytocannabinoids, their ability to induce antiproliferative effects in different human cancer cells raises the scientific interest in their therapeutic potential in the field of oncology.”

https://www.mdpi.com/1422-0067/23/13/7145

“Although cannabinoids have been used for centuries for diverse pathological conditions, recently, their clinical interest and application have emerged due to their diverse pharmacological properties. Indeed, it is well established that cannabinoids exert important actions on multiple sclerosis, epilepsy and pain relief.

Regarding cancer, cannabinoids were first introduced to manage chemotherapy-related side effects, though several studies demonstrated that they could modulate the proliferation and death of different cancer cells, as well as angiogenesis, making them attractive agents for cancer treatment.

In relation to breast cancer, it has been suggested that estrogen receptor-negative (ER^–) cells are more sensitive to cannabinoids than estrogen receptor-positive (ER⁺) cells. In fact, most of the studies regarding their effects on breast tumors have been conducted on triple-negative breast cancer (TNBC). Nonetheless, the number of studies on human epidermal growth factor receptor 2-positive (HER2⁺) and ER⁺ breast tumors has been rising in recent years. However, besides the optimistic results obtained thus far, there is still a long way to go to fully understand the role of these molecules. This review intends to help clarify the clinical potential of cannabinoids for each breast cancer subtype.”

https://pubmed.ncbi.nlm.nih.gov/35011388/

“Cannabinoids have been used for centuries in several therapeutic applications. Regarding cancer, the use of cannabinoids has already been approved in several countries for the relief of chemotherapy-associated effects, but their clinical potential is greater than initially thought, and their clinical interest has been rising in recent years. Pre-clinical studies have demonstrated that cannabinoids exert important antitumor properties in the main breast cancer subtypes, particularly in TNBC, where different phytocannabinoids and synthetic cannabinoids have shown interesting therapeutic actions.”

“Thus, it is strongly believed that Cannabis, being an important natural source of many cannabinoids, may be a potential therapeutic option for the treatment or modulation of different physiological processes and, even, pathological conditions, such as cancer.”

https://www.mdpi.com/1420-3049/27/1/156

“Experimental evidence accumulated during the last decade supports that cannabinoids, the active components of Cannabis sativa and their derivatives, possess anticancer activity. Thus, these compounds exert anti-proliferative, pro-apoptotic, anti-migratory and anti-invasive actions in a wide spectrum of cancer cells in culture. Moreover, tumor growth, angiogenesis and metastasis are hampered by cannabinoids in xenograft-based and genetically-engineered mouse models of cancer. This review summarizes our current knowledge on the anti-tumor potential of cannabinoids in breast cancer, which suggests that cannabinoid-based medicines may be useful for the treatment of most breast tumor subtypes.”

https://www.sciencedirect.com/science/article/pii/S0305737212001399

“Purpose/objective(s): Cannabis use among patients with cancer is an area of great interest given its widespread acceptance despite the lack of supporting clinical data. The absence of data limits the understanding of potential clinical benefits of cannabis and the ability of providers to deliver evidence-based recommendations for patient care. We explored cannabis use patterns in patients with early-stage breast cancer in a large multicenter cohort in a state with legalized adult non-medical cannabis.

Materials/methods: Initial questions about cannabis use history and frequency were introduced in Michigan Radiation Oncology Quality Consortium (MROQC) breast cancer patient surveys on 2/1/2020 for female patients receiving radiation after lumpectomy for non-metastatic breast cancer. Expanded questions were introduced on 6/28/2022 to assess mode of administration, active ingredient, and reason for use. Summary statistics were generated. A multivariable model using logistic regression identified patient characteristics associated with cannabis use.

Results: Among 3948 eligible patients, 2738 (69.35%) completed survey questions, and 2462/2738 (89.9%) completed the initial question on cannabis use. Among those, 364/2462 (14.8%) noted cannabis use in the last 30 days, 588 (23.9%) noted remote use (>30 days ago), 1462 (59.4%) reported never having used cannabis, 44 (1.8%) preferred not to answer cannabis use questions, and 4 (0.4%) did not provide use history. Younger age [age <50 vs 60-70, OR 2.5 (95% CI 1.65, 3.79) p<0.001)], Hispanic ethnicity [OR 2.20 (95% CI 1.06, 4.56) p = 0.03], history of smoking [OR 2.56 (95% CI 1.88, 3.48) p<0.001], current smoking [OR 4.70 (95% CI 3.22, 6.86) p<0.001)], and prior chemotherapy [OR 1.40 (95% CI 1.00, 1.96) p = 0.05] predicted recent cannabis use in a multivariable model. Of the 364 patients endorsing cannabis use in the last 30 days, 89 (24.5%), 72 (19.8%), 29 (8.0%), 66 (18.1%), 30 (8.2%), and 78 (21.4%) reported using cannabis 1-2 days, 3-5 days, 6-9 days, 10-19 days, 20-29 days, and all 30 days, respectively. The most common modes of administration among 76 individuals who responded to the expanded questionnaire to date were oral (39.4%), smoking (30.3%), and topical (10.5%). The products used contained tetrahydrocannabinol (THC; 26.3%), cannabidiol (CBD; 19.7%), balanced levels of THC and CBD (19.7%), or active ingredients that were unknown to the patient (34.2%). Patients frequently endorsed cannabis use for insomnia, anxiety, and pain.

Conclusion: Many patients with early-stage breast cancer are using cannabis. Younger age, Hispanic ethnicity, smoking, and chemotherapy history are predictors of cannabis use. Patients are often unaware of the active ingredients in the products that they use, suggesting an important role for patient education and a need to equip providers to advise patients in their care.”

https://pubmed.ncbi.nlm.nih.gov/37786222/

https://www.redjournal.org/article/S0360-3016(23)05292-6/fulltext

“Inflammation is a critical component of cancer development. Previously, we showed in vitro that IL-1β treatment of non-invasive human breast cancer MCF-7 cells promoted their transition to a malignant phenotype (6D cells). This epithelial-mesenchymal transition was reverted by exposure to cannabidiol (CBD).

We show in a murine model that subcutaneous inoculation of 6D cells induced formation and development of tumors, the cells of which keep traits of malignancy. These processes were interrupted by administration of CBD under two schemes: therapeutic and prophylactic. In the therapeutic scheme, 6D cells inoculated mice developed tumors that reached a mean volume of 540 mm³ at 45 days, while 50% of CBD-treated mice showed gradual resorption of tumors. In the prophylactic scheme, mice were pre-treated for 15 days with CBD before cells inoculation. The tumors formed remained small and were eliminated under continuous CBD treatment in 66% of the animals. Histological and molecular characterization of tumors, from both schemes, revealed that CBD-treated cells decreased the expression of malignancy markers and show traits related with apoptosis.

These results confirm that in vivo CBD blocks development of breast cancer tumors formed by cells induced to malignancy by IL-1β, endorsing its therapeutic potential for cancer treatment.”

https://pubmed.ncbi.nlm.nih.gov/37686042/

“In conclusion, the present study shows that CBD, properly administered, can effectively block development of human breast cancer tumors in vivo, without causing adverse effects, by regulating in the tumor cells the expression of malignant traits and bearing characteristics of a possible route via apoptosis, both favorable attributes for an anticancer drug.”

https://www.mdpi.com/1422-0067/24/17/13235