Scientists are investigating whether cannabinoid signaling can influence how breast cancer cells behave, rather than simply trying to destroy them. A new study suggests that brief exposure to very low concentrations of THC can shift some breast cancer cells toward a less plastic and less aggressive state in experimental models.
The research, published in Communications Biology, focused on cancer cell plasticity — the ability of tumor cells to move between different cellular states, including states with stem-like characteristics. Such plasticity has been implicated in tumor progression, treatment resistance, recurrence and metastasis, making the processes that regulate cell identity an important area of cancer research.
To investigate these mechanisms, the researchers used mammary tumor organoids, three-dimensional models grown from human and mouse breast cancer cells. They exposed the organoids to low concentrations of THC for four days and examined subsequent changes in properties including invasiveness, self-renewal and tumor-initiating capacity.
How THC interacts with cancer cells
The experiments centered on the endocannabinoid system, a signaling network involved in numerous physiological processes. It includes the cannabinoid receptors CB1R and CB2R, which can respond to endogenous cannabinoids as well as compounds such as THC.
The researchers used different ligands to alter cannabinoid receptor signaling and observed how the tumor cells responded. Following brief, low-dose THC exposure, the organoids showed reduced invasiveness and a reduced capacity to initiate tumors, changes consistent with a shift away from highly plastic, stem-like cellular states.
The results implicated signaling associated with CB2R in these effects. CB1R, by contrast, is the cannabinoid receptor more strongly associated with the psychoactive effects of THC.
Pharmacological manipulation of CB2R signaling, including the use of an inverse agonist that reduces constitutive receptor activity, reproduced some of the cellular changes associated with THC exposure. Manipulating CB1R did not produce the same pattern.
A complex role for CB2R signaling
The relationship between CB2R and the observed effects was not straightforward. Organoids derived from mice genetically engineered to lack CB2R also displayed changes toward less aggressive cellular behavior.
This finding indicates that the mechanism cannot be explained simply by THC activating CB2R. Instead, the results point to a more complex relationship involving cannabinoid signaling, baseline receptor activity and potentially additional molecular pathways.
The researchers interpret the findings in the context of cancer cell plasticity. Tumor cells can occupy different cellular states and transition between them, and changes in signaling may alter the balance between more stem-like and more differentiated states.
Under this model, manipulating cannabinoid-related pathways could potentially influence the state adopted by a population of cancer cells rather than directly killing those cells.
Effects extend beyond cultured organoids
The researchers also investigated whether the cellular changes observed in organoids influenced tumor behavior in animals.
When experimentally treated organoids were transplanted into cancer-prone mice, differences in subsequent tumor development were observed compared with control conditions. Tumors derived from treated cells appeared later and showed reduced growth and less aggressive characteristics.
In separate experimental models examining metastatic behavior, treated cells also produced fewer lung metastases.
These animal experiments provide additional evidence that short-term manipulation of cannabinoid-related signaling can have longer-lasting effects on tumor-cell behavior. However, results from organoids and mouse models cannot establish whether the same effects would occur in people with breast cancer.
Possible implications for hormone therapy
The study also identified a potential connection between cannabinoid-related signaling and estrogen receptor activity in some breast cancer cells.
CB2R-associated modulation was linked to increased estrogen receptor activity under certain experimental conditions. This was accompanied by changes that could potentially affect responsiveness to endocrine treatments such as tamoxifen.
The finding raises the possibility that altering tumor-cell states could eventually be investigated alongside established hormone-based treatments. If cancer cells can be shifted toward more differentiated states that remain sensitive to existing therapies, manipulating cellular plasticity could potentially complement approaches designed to kill or suppress tumor cells.
However, these experiments do not demonstrate that THC improves tamoxifen treatment in breast cancer patients, nor do they establish a cannabinoid-based combination therapy. Further studies would be required to determine whether the observed molecular effects translate into clinically meaningful treatment responses.
The findings do not support cannabis as a cancer treatment
The study should not be interpreted as evidence that using cannabis can treat breast cancer. The experiments involved controlled concentrations, specific tumor models and carefully defined exposure conditions that are fundamentally different from recreational or medical cannabis use.
THC also affects multiple biological systems and can produce psychoactive and other physiological effects. A compound capable of influencing a pathway in cultured cells or mice is not necessarily safe or effective as a cancer treatment in humans.
Instead, the research identifies cannabinoid-related signaling as a potential biological pathway for further investigation. Future work could determine which molecular components are responsible for the observed changes and whether more selective compounds could reproduce desirable effects without the broader actions of THC.
The study contributes to a growing area of cancer research focused on cellular plasticity. Rather than exclusively attempting to eliminate malignant cells, researchers are investigating whether some tumors can also be made less dangerous by influencing the cellular states that support invasion, treatment resistance and metastasis.
For now, the findings provide experimental evidence that brief manipulation of cannabinoid signaling can alter breast cancer cell behavior in organoid and animal models. Whether this approach can eventually contribute to safe and effective therapies for people with breast cancer remains an open question.