CANCER OF THE SKIN

Our bodies have cozied into this Earth, perfectly suited to thrive through the seasons. Nevertheless, our environment is harsh. Even those with the healthiest lifestyles confront toxins in the air we breathe—and the sun, our source of warmth, bombards us with UV rays that can damage DNA and mutate our skin.

These mutations are like a roulette wheel. The universe casts a ball of UV rays, and the ball bounces its way to an outcome. If it lands on red, our skin cells repair and live. If it lands on black, they die, and healthy cells take their place. But every so often, it lands on green, and the mutated cells don’t repair or die. They divide like a virus, clearing out normal tissue, feeding on the nutrients, and forming a cancerous, malignant tumor.

If you find that prospect terrifying, you’re not alone. No one likes to be out of control, but thankfully, it’s not a perfect metaphor. As long as you’re not using a tanning bed—if you are, please stop!—an occasional day without sunscreen or one sunburn rarely causes melanoma, the tumors most associated with skin cancer.

Why? To form cancer, mutated cells must do two things: they must grow rapidly, and they must escape our body’s internal security measure of programmed cell death.

Biologically, that’s not like a roulette wheel, where 1 in 37 slots are green. It’s more like being struck by lightning in your lifetime, which happens to 1 person in 3,000. 1 The likelihood you develop skin cancer depends on many factors, like how consistently your skin

is damaged—playing roulette over and over—and your genetic makeup. For example, people born with a mutated MC1R gene, which is almost all people with red hair and fair skin, are 2–15 times more likely to develop melanoma. 2

So what can you do, besides wearing sunscreen? You can be on the lookout for signs of an abnormal mole and see a dermatologist regularly. 3 If they spot something suspicious, they can remove it and test if it’s malignant. If caught before the cancer has spread, there’s a 98% cure rate. 4 But it’s more serious if the cancer has spread to the lymph nodes and beyond, most often to the brain, liver, and bones. 5

Metastatic melanoma is aggressive and doesn’t respond well to normal chemotherapy. Only 1 in 4 people survive 5 years, 4 and most don’t live beyond a year. 5 Your best bet? Modern therapies and clinical trials. Scientists have developed new medicines such as immune checkpoint inhibitors, which can give your immune system back its power to fight cancer cells. Modern therapies can cure—but they are expensive, can have serious side effects, and are not always effective.

In a major clinical study of the immunotherapy agent pembrolizumab (Keytruda), only 16% of melanoma patients went into remission. But 42% of patients didn’t respond at all, and 25% dropped out of the study due to side effects. 6

Doctors might be excited by these breakthrough therapies, but if you’re fighting for your life and that roulette game is on tilt, you’d search for anything that could help save your life. Enter: cannabis, specifically THC, CBD, and cannabis’ other components.

To the most skeptical among us, myself included, this may sound like snake oil, but there is scientific evidence that cannabis can fight skin cancer. Studies of mice with melanoma show that THC treatment was as effective as temozolomide (TMZ) chemotherapy in stunting cancer growth. Further, THC combined with CBD in a one-to-one ratio (meaning equal parts THC and CBD, like Sativex) 7 was even more effective. 8 These treatments alone could not cure melanoma, but think about that for a second: THC was as effective as chemotherapy.

How is that possible? Remember that cancer cells must bypass programmed cell death. TMZ chemotherapy damages DNA, so when cancer cells divide, they’re more likely to die. THC and CBD cause the same thing to happen but by an entirely different mechanism. They

interact with cannabinoid receptors in the ECS that act like light switches, illuminating a pathway to cell death that’s normally shut off. 9 Along with other cancers, melanoma cells have an abundance of cannabinoid receptors not found on normal skin cells, and this makes them susceptible to cell death via THC and CBD. 10

With any cancer treatment, there is a risk of resistance. Even within one person’s tumor, not all cancer cells are identical. As the cancer grows, it accumulates new mutations in a sped-up evolution. A few cancer cells can develop mutations that make them resistant to one therapy. So even if that therapy kills most of the cancer cells, those few resistant cells can go on to form a new tumor that is harder to treat, much like antibiotic-resistant bacteria.

Cannabis is no exception. Researchers have observed resistance to cannabis after treating brain cancer cells. They suggested that combining cannabis with other therapies could help avoid relapse. 11 This approach is promising because the likelihood that a cancer can randomly develop resistance to two therapies is much less. Combining THC with TMZ to treat mice with brain cancer produced remarkable results. Alone, they curbed cancer growth, but together they actually shrunk the tumor! 9 And that, frankly, is amazing.

A word of caution: these studies were preclinical, meaning the studies weren’t done with humans, and there are some big differences between mice and humans. Despite mounting evidence that cannabis can help stop cancer cells, there aren’t many studies in humans. Humans have used cannabis for millennia, but criminalization has stunted research. If you search for clinical trials involving cancer and cannabis, 12 they are restricted to palliative care, such as treating pain and nausea. 11 Almost four years after the preclinical evaluation of Sativex to drive melanoma cell death in mice, 8 similar studies in humans have not begun.

For many scientists and clinicians, there are too many unknown factors and contradicting data to stake a scientific backing on using cannabis to treat skin cancer in humans, especially for aggressive cancers such as melanoma. 13

But unlike them, it is not my job to make a steadfast decision for you. My job is to use my scientific background to relay evidence. Cannabis appears effective in combating skin cancer, but it’s probably not a silver bullet. The most promising results have been achieved by combining cannabis with a first-line chemotherapy agent to mount a synergistic assault on the cancer and avoid resistance.

If you or a loved one are battling skin cancer, my heart goes out to you, and if you are considering using cannabis as a treatment, talk with your doctor. They might not suggest cannabis without prompting, but they’re likely open to talking about it. After all, there is some striking evidence to consider.

References: 1. https://www.cancer.org/cancer/melanoma-skin-cancer/about/key-statistics.html 2. Box, Neil F., Wei Chen, Richard A. Sturm, David L. Duffy, Rachel E. Irving, Anne Russell, Lyn R. Griffyths, Peter G. Parsons, and Adele Green. “Melanocortin-1 Receptor Genotype Is a Risk Factor for Basal and Squamous Cell Carcinoma.” Journal of Investigative Dermatology 116, no. 2 (2001): 224-29. doi:10.1046/j.1523-1747.2001.01224.x. 3. https://www.skincancer.org/skin-cancer-information/atypical-moles/warning-signs-and-images 4. https://www.cancer.org/cancer/melanoma-skin-cancer/detection-diagnosis-staging/survival-rates-for-melanoma-skin-cancer-by-stage. html 5. Tas, Faruk. “Metastatic Behavior in Melanoma: Timing, Pattern, Survival, and Influencing Factors.” Journal of Oncology (2012): 647684. doi:10.1155/2012/647684. 6. Hamid, Omid, Caroline Robert, Adil Daud, F. Stephen Hodi, Wen-Jen Hwu, Richard Kefford, Jedd Wolchok, Peter Hersey, Richard Joseph, Jeffrey Weber, et al. “Five-Year Survival Outcomes for Patients with Advanced Melanoma Treated with Pembrolizumab in KEYNOTE-001.” Annals of Oncology 30, no. 4 (2019): 582-88. doi:10.1093/annonc/mdz011. 7. https://www.gwpharm.com/healthcare-professionals/sativex# 8. Armstrong, Jane L., David S. Hill, Christopher S. McKee, Sonia Hernandez-Tiedra, Mar Lorente, Israel Lopez-Valero, Maria E. Anagnostou, Fiyinfoluwa Babatunde, Marco Corazzari, Christopher P.F. Redfern, et al. “Exploiting Cannabinoid-induced Cytotoxic Autophagy to Drive Melanoma Cell Death.” Journal of Investigative Dermatology 135, no. 6 (2015): 1629-37. doi:10.1038/jid.2015.45. 9. Blázquez, Cristina, Arkaitz Carracedo, Lucía Barrado, Pedro J., Real, José L. Fernández-Luna, Guillermo Velasco, Marcos Malumbres, and Manuel Guzmán. “Cannabinoid Receptors as Novel Targets for the Treatment of Melanoma.” The FASEB Journal 20, no. 14 (2006): 2633-35. doi:10.1096/fj.06-6638fje. 10. Zhao, Zigang, Jie Yang, Hua Zhao, Xiangdong Fang, and Hengjin Li. “Cannabinoid Receptor 2 Is Upregulated in Melanoma.” Journal of Cancer Research and Therapeutics 8, no. 4 (2012): 549-54. doi:10.4103/0973-1482.106534. 11. Velasco, Guillermo, Claudia Sánchez, and Maria Guzmán. “Anticancer Mechanisms of Cannabinoids.” Current Oncology 23, no. 2 (2016). doi:10.3747/co.23.3080. 12. https://clinicaltrials.gov/ 13. ”CBD Uncertainty: Sales Soar But Science Lags On Hemp Health Effects.” WFPL News Louisville. April 15, 2019. https://wfpl.org/cbduncertainty-sales-soar-but-science-lags-on-hemp-health-effects/