The heterogeneity of Cannabis extracts as antitumor agents

Introduction

It is well established that cannabinoids, the active compounds in Cannabis spp., display a variety of biological effects by mimicking endocannabinoids. Cannabis plants contain more than 100 distinct cannabinoids. Yet, the identification of Cannabis components are usually limited to several major cannabinoids. Recently, the therapeutic potential of cannabinoids has been rediscovered in cancer research as these compounds were found to have palliative effects in oncology. However, there is also accumulating evidence showing possible cannabinoid-induced antitumor effects. In response to cannabinoids, several studies showed a regression of different tumor types in vivo. Further investigations in vitro have revealed that they can induce cell death and inhibit proliferation of cancer cells. The concentrations and combinations of various cannabinoids determine both medicinal and adverse side effects in patients. Therefore, analyzing the chemical content of differing whole Cannabis plants is of major importance.

In this work we established a mini-profile with ten different cancer lines to quantitatively and functionally evaluate the effect of various Cannabis extracts and thereby determine whether Cannabis might be advantageous as an additional treatment for certain cancers.

Materials and methods

We perfected extraction techniques and identified distinct compositions of 12 clinically-used Cannabis extracts. We then explored the differential antitumor effects of these Cannabis extracts (differing in cannabinoid compositions) on 12 cancer cell lines of six solid cancer types.

Results and Discussion

Cannabis strains vary significantly in their cannabinoid composition. Depending on the applied concentrations, results indicated that certain Cannabis extracts have statistically different (p < 0.0001) effects on cancer cell survival. In addition, differing cancer cell lines vary in sensitivity to various Cannabis extracts. For example, treatment with one Cannabis extract (4 µg/mL) resulted in cancer cell death ranging from 3% to 45% (LNCaP and PC3 cell lines, respectively). We also found specific cell lines that were resistant to all tested extracts. Furthermore, whole Cannabis extracts with high content of Δ⁹-Tetrahydrocannabinol were found to be more potent at lower concentrations (4 µg/mL) in comparison to using purified Δ⁹-Tetrahydrocannabinol (8 µg/mL) to produce the same amount of cell death when applied to specific cancer cell lines.

Conclusions

Cannabis is a heterogeneous array of therapeutic agents. The efficacy of these agents is strongly dependent on the cell type utilized. Categorizing cancer cells according to their response to specific cannabinoid composition will provide valuable information for the development specific Cannabis treatments for subgroups of cancer patients.