Topical Cannabinoids for Melanoma? Be Careful

Cannabinoids need help penetrating the skin barrier. And they need help staying there long enough to do good work.  

Melanoma is an aggressive form of skin cancer for which there are limited treatment options. It is deadly because it often metastasizes before detection. Applying cannabinoids like cannabidiol (CBD) or delta-9-tetrahydrocannabinol (THC) to the skin has been proposed for the treatment of a variety of skin issues and diseases from acne to psoriasis, but does its cancer fighting properties apply to skin cancers?

For cannabinoids to effectively treat melanoma, the cancer cells need to express the cannabinoid receptors CB1 and CB2. Studies of the skin have found that CB1 and CB2 receptors are indeed expressed by various types of skin cells and subcutaneous nerve cells.

Scientists have also verified the presence of CB1 and CB2 receptors in melanoma cells. This suggests that we could utilize cannabinoids to target these cells. The presence of these receptors suggests that the endocannabinoid system has a normal function in maintaining the health of our skin. One hypothesis is that endocannabinoids involve the normal differentiation of keratinocytes. This is the process that produces and maintains our protective layer of skin cells.

Skin cells, and melanoma cells in particular, express cannabinoid receptors. Because of this, scientists are working on several preclinical studies of the effects of cannabinoids on melanoma. Many of these studies used melanoma cells growing in vitro, or in cell culture plates in a lab. Treating melanoma cells with cannabinoids (like THC) reduces the proliferation of the cells by slowing down their growth and division.

Cannabinoids Don’t Stop Healthy Cell Division

Interestingly, cannabinoids do not stop the growth and division of healthy cells. This makes it the ideal treatment for cancer. The way cannabinoids “know” which cells to kill is thought to be the inhibition of a cell survival pathway that involves the Akt protein, which is overactive in most cases of melanoma. Another laboratory study found that treating melanoma cells with THC was able to trigger cell death by activating a process called autophagy, in which the cell breaks down its worn out or damaged components. In certain circumstances, autophagy can also lead to cell death, which the researchers found was the case with melanoma.

In addition to slowing the growth of melanoma tumors, cannabinoids may have anti-metastatic effects. Scientists  have examined these with respect to melanoma and other cancers. One study on melanoma cells in particular found that treating these cells with Cannabis extract reduced the expression of metastasis-promoting proteins. Since metastasis is usually the deciding factor in the fatality of the disease, slowing down this process is critical.

Most pre-clinical melanoma studies performed on animals simply inject cannabinoids directly into the tumor or into the blood stream. In vitro cell studies supply the cannabinoids in the growth media that surrounds the cells. None of these studies examine skin-surface application; and whether cannabinoids can permeate the skin in order to reach the cancerous cells.

CBD Permeates a Little Too Well

However, the transdermal application of cannabinoids, like CBD or THC, is desirable for many other applications. This means that there already are some studies on the diffusion of CBD through healthy skin. These studies demonstrate that CBD has good permeability through human skin.  Therefore, you could administer a significant dose of CBD this way. However, most of the CBD then enters the blood stream.

For the CBD to remain on the skin we’ll need different formulations. These do not yet exist. The same goes for potentially staying in the melanoma tumor. Due to higher hydrophobicity, CBD suspensions in oil may be preferable to slow down the diffusion through the skin. For example, one study found that higher levels of delta-8-tetrahydrocannabinol (delta-8-THC) and cannabinol (CBN) remained in the skin after a diffusion experiment. Compared to CBD these molecules are more hydrophobic.

Melanoma Study Conclusions

There are numerous studies on cells and laboratory animals. There have not yet been any human clinical trials to assess the efficacy of cannabis for treating melanoma. Preclinical studies indicate that cannabinoids, like CBD, could help to slow the growth of the cancer. These results however, do not demonstrate that CBD could lead to a cure on its own.

The skinreadily absorbs CBD and other cannabinoids. However, topical application could be a good approach to targeting lesions. At this time there is not enough data. Therefore we can’t suggest we have high enough concentrations of CBD to slow the skin cancer growth.