Cannabis compounds including cannabidiol (CBD) and tetrahydrocannabidiol (THC) show anticancer activity against cervical cancer cells in multiple laboratory studies, including triggering cancer cell death and reducing invasion, according to a review published this month in the Journal of Cannabis Research.
The review was conducted by researchers from the University of KwaZulu-Natal, Simon Fraser University, Nelson R. Mandela School of Medicine and the Africa Health Research Institute.
For the review, researchers searched PubMed, Scopus, Web of Science, ScienceDirect and Google Scholar for peer-reviewed studies examining marijuana-derived compounds, cannabinoids or the endocannabinoid system in cervical cancer models. Five studies met the inclusion criteria.
Across the studies, cannabis extracts and cannabinoids were found to reduce cervical cancer cell viability, trigger programmed cell death and interfere with processes involved in cancer cell invasion.
One study found that purified CBD induced significant apoptosis and cell death in HeLa, SiHa and ME-180 cervical cancer cell lines, with concentrations producing a 50% inhibitory effect ranging from 1.5 to 3.2 micrograms per milliliter. CBD was more potent in that experiment than crude Cannabis sativa extracts, which had IC50 values ranging from 50 to 100 micrograms per milliliter.
Another study found that 10 micromolar CBD significantly inhibited the invasion of HeLa and C33A cervical cancer cells. Researchers linked the effect to increased expression of tissue inhibitor of metalloproteinases-1, or TIMP-1, through MAPK signaling pathways involved in regulating cell growth and survival.
CBD-enriched hemp oil also reduced HeLa cell viability while increasing hydrogen peroxide and oxidative stress, suggesting that reactive oxygen species and mitochondrial dysfunction may contribute to cannabinoid-induced cancer cell death.
A THC-rich cannabis extract tested against HeLa, SiHa and C33A cells showed IC50 values of 3.1 micrograms per milliliter or less, along with selectivity indices ranging from 25.9 to 48.9. Another cannabis extract was found to induce apoptosis in HeLa cells at an IC50 of 49 micrograms per milliliter.
The review also highlights the complexity of the endocannabinoid system. While pathways involving TRPV1 activation and reactive oxygen species were generally associated with cancer cell death, activation of CB1 and CB2 receptors appeared capable of producing protective, anti-apoptotic effects under some conditions. Researchers said cannabinoid signaling therefore cannot be assumed to be uniformly anticancer.
Researchers emphasized that all five studies were conducted in cell cultures. No animal studies examining Cannabis sativa or its phytocannabinoids specifically in cervical cancer models were identified, and differences in cannabis composition, extraction methods, cannabinoid concentrations and cancer cell lines make direct comparisons difficult.
The authors concluded that cannabis-derived compounds, particularly CBD and THC, “can modulate key cellular processes, including apoptosis, oxidative stress, and invasion.” However, they cautioned that the effects are “highly context-dependent” and that the evidence remains preliminary, with all of the available studies limited to in vitro models. They called for animal studies, research involving HPV-associated cervical cancer models and pharmacokinetic studies to better determine the potential clinical relevance of cannabinoids.
