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Cannabis & Cancer: Cause, Cure, Conundrum

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Written by Garth Sundem on December 14, 2015

Within two miles of the University of Colorado Cancer Center are at least seven recreational marijuana dispensaries with names like Pink House, Terrapin Care Station, Sweet Leaf, Lightshade and Starbuds. And the influence of what happens off campus doesn’t stay off campus. Our patients are using marijuana – some recreationally, some to alleviate the symptoms of cancer and cancer treatments, and some with the belief that cannabis and cannabis-based products could improve or cure their disease.

We can’t ignore the fact that here on the Anschutz Medical Campus we are at the absolute epicenter of cannabis in the United States. So for a few minutes let’s put aside the pot jokes. Let’s put aside the moral, societal and political right and wrong of medical and recreational marijuana legalization in Colorado and beyond. Let’s even put aside the negative and positive health effects of marijuana in conditions beyond cancer. For a few minutes, let’s focus on what we know, what we don’t know, and what we would desperately like to know about cannabis specifically in the context of cancer.

How Cannabis Works

To understand the effects of cannabis on cancer, we first have to know how the chemicals inside the cannabis plant work.

Every cell in your body bristles with little mailboxes, each shaped to receive a different kind of letter. One kind of mailbox accepts adrenaline (which makes you energized), another accepts dopamine (which makes you pleasantly happy), and another accepts caffeine (which makes it possible to exist on Tuesdays). In fact, there are hundreds of these mailboxes – called “receptors” – and thousands of chemicals that are like the letters that fit inside (called “ligands”).

When a receptor receives a ligand, it triggers the cell to act in a certain way. In short, this system of mailboxes and letters (receptors and ligands) helps your body eat, sleep, love, fight, learn and, basically, function.

One group of these paired receptors and ligands makes up what is called the endocannabinoid system. This system of cell communication is involved in regulating things like memory, appetite, energy, stress, sleep and pain. If this sounds like a behavioral checklist from a Cheech and Chong film, that’s because the chemicals in marijuana directly affect the endocannabinoid system.

In fact, many chemicals activate our cell signaling systems by looking enough like a ligand to fit a receptor. Caffeine stimulates receptors that usually watch for a ligand called adenosine. The breast cancer drug tamoxifen blocks receptors that watch for the ligand estrogen. And the tetrahydrocannabinol (THC) in marijuana stimulates receptors of the endocannabinoid system that naturally watch for the ligand anandamide. THC is the ingredient in marijuana responsible for the feeling of being high, but it’s far from the only active ingredient.

Many more chemicals inside the cannabis plant look enough like anandamide to activate the endocannabinoid system. There are 66 different cannabinoids that interact with the endocannabinoid system. Like THC, the full chemical names are long and un-pronounceable, but each one delivers a slightly different message and has a slightly different effect on the endocannabinoid system.

So now the question is…what are these effects?

Does Cannabis Cause Cancer?

Some cancers learn to manufacture more receptors or more ligands in ways that tell cells to survive and replicate beyond their natural bounds. This bad cell signaling is a common cause of the disease. But according to current knowledge, it doesn’t look like the endocannabinoid system is related to cell survival and growth, so on a cellular level, cannabis-based drugs seem unlikely to cause cancer.

However, there’s another aspect of cannabis use that is 100 percent proven to increase cancer risk: inhaling smoke from burning plant products.

“Over 95 percent of cannabis users smoke it. There are the same products in marijuana smoke as there are in tobacco cigarettes, so they’re in effect smoking cigarettes without the nicotine. It’s not that marijuana is somehow more natural and so healthier. You would expect marijuana to have the same impact on the development of lung cancer,” says Ellen Burnham, MD, MS, pulmonologist and medical director for the University of Colorado Hospital Intensive Care Unit.

Burnham came to marijuana research in an interesting way.

“Most of my research has to do with alcohol’s effect on the lung,” Burnham says. When enrolling people in her studies, her group asked about marijuana use. “And, maybe due to increased use or due to increased social acceptability of use, we saw many more patients in our studies admitting they used marijuana.” Burnham realized that data she was already collecting would allow her to explore the effect of marijuana smoking on the lung. “We were looking at what alcohol does and now we could look at what cannabis does too,” she says.

Here is what she found: “Modest consumption of cannabis may have minimal impact to lung health,” Burnham writes in a May 2015 review of the effects of cannabis on lung health in the journal Chest. However, she also writes that, “mainstream cannabis smoke contains substantially higher quantities of ammonia, hydrogen cyanide, NO, and NOx than comparable cigarette smoke, implying a more toxic effect from cannabis.”

Burnham’s review matches most publications that explore the influence of marijuana on lung cancer risk, which (very generally) find a slight but not extreme increase in lung cancer among marijuana smokers. The reason may be that most cannabis users inhale less smoke per day than most tobacco users. To further decrease the risk, some patients who use cannabis in medical settings use vaporized dosing and/or edibles.

“What worries me is that recent legislation legalizing marijuana makes it seem safe,” Burnham says. “Until we know more, I would have a hard time as an oncologist recommending it.”

Can Cannabis Control Cancer Symptoms?

About one-third of cancer patients will experience chronic pain. This pain can come from the cancer itself as it destroys tissue or as masses put pressure on nerves, bone and muscle, or pain can come from cancer treatments like surgery and radiation. It can be sharp or dull, intermittent or ever-present. Cancer pain may be controlled by over-the-counter meds or it may require heavy-duty, opioid-based painkillers like morphine, oxycodone or fentanyl, which carry the risk of addiction and other side effects. Some researchers hope that cannabis-based drugs could provide another option for controlling cancer pain. Some doctors and patients think that cannabis already does.

“For pain, nausea and appetite, there’s pretty good evidence that cannabinoids are effective,” says Tim Byers, MD, cancer epidemiologist and co-program leader in Cancer Prevention and Control at the CU Cancer Center.

Just like opioids, the question is at what cost. On a basic level one very likely side effect of cannabis use in a pain-control setting is that the patient will get high. Many cancer patients need a 24/7, long-term solution for their pain and for some people it may be undesirable or impractical to be constantly stoned. “People say they don’t want to feel high all the time, but will accept it instead of being in pain,” Byers says.

One solution may be drugs derived from cannabis that include the chemicals that control pain but exclude the chemicals that cause disorientation, light-headedness, or euphoria.

“Even now, people pick strains of cannabis based on how they want to feel. For those people who use it medicinally to improve sleep or PTSD or chronic pain or seizures, they don’t want to be high all the time and so they take forms that are high in cannabidiol (CBD) and lower in THC,” Byers says.

Many modern pharmaceuticals are derived from or synthesized to replicate the properties of plant-based products. In fact, 11 percent of the 252 drugs considered basic and essential by the World Health Organization are derived from flowering plants. Many researchers hope that similar potential exists for pain medications derived from cannabis.

“There’s potential for marijuana pharmaceuticals derived from cannabinoids. Right now they don’t appear to be as effective as the plant product itself but I’m sure there will be new formulations in the future,” Byers says.

Before moving on, let’s tally the score: Does cannabis cause cancer? When used in moderation, maybe a little but almost certainly not a lot. Can cannabis or cannabis-based drugs control cancer-associated pain? Yes, and they’ll probably get better in the future. Now onto the question that has probably kept you reading this article:

Can Cannabis Cure Cancer?

“I had a patient, a young guy with metastatic head and neck cancer. There were treatment options available but instead this guy insisted on treating himself with cannabis oil,” says Daniel Bowles, MD, assistant clinical professor of medical oncology at the CU School of Medicine.

Some evidence supports this patient’s opinion that cannabis could cure his cancer. In fact, there are papers published in the respected, peer-reviewed journals Oncogene, The Proceedings of the National Academy of Sciences, The British Journal of Cancer and many more showing that THC or cannabinoids of various sorts kill cancer cells. The thing is, there are many things that kill cancer cells (a flamethrower is one of them), and many therapies that are slam dunks in mice don’t pan out in humans.

Unfortunately, it’s easy to Google for studies of cannabis-based products that seem promising against cancer, but it’s horribly difficult to read between the lines of science-ese to know what these studies actually mean. And in that space of ambiguity, it’s easy to read into a study what you want to hear. That’s how a paper titled “The Combination of Cannabidiol and Δ9-Tetrahydrocannabinol Enhances the Anticancer Effects of Radiation in an Orthotopic Murine Glioma Model” (Molecular Cancer Therapeutics, 2014) becomes a news article titled “Marijuana Drastically Shrinks Aggressive Form of Brain Cancer, New Study Finds” (Huffington Post, 2014). The first is a study of cancer cells pretreated with THC and/or cannabidiol before irradiation. The second implies that smoking pot will kill brain cancer. Beyond these promising early studies, the National Cancer Institute writes that, “No clinical trials of Cannabis as a treatment for cancer in humans are identified.”

Call it hash oil, Simpson oil, phoenix tears or any other name: Dr. Bowles’ patient with metastatic head and neck cancer who chose self-medication with marijuana rather than the established cancer treatment died.

“The most unfortunate slice of our population is the people moving here under the impression that cannabis oil will cure their children,” says Nicholas Foreman, MD, pediatric neuro-oncologist at Children’s Hospital Colorado. “Based on the current evidence, I would say there is no potential for curative therapies. Hope comes from a few number of feeble studies that are then passed up and down the internet. This is how we end up with great enthusiasm for something with no evidence at all.” (Bookmark this quote in your mind – we’ll hear more from Foreman later.)

Of course, and let’s be fair here, some therapies discovered in a dish and tested on mice do go on to save human lives. In fact, this is (generally) the workflow of modern medicines: Work with basic biology creates a hypothesis, the hypothesis is tested on cells in a dish, a possible medicine based on this hypothesis is discovered or designed, the drug is tested in mice, the drug enters human clinical trials, the drug is approved by the FDA, then it becomes a common treatment. Only, right now the progression of cannabis-based drugs is stalled partway along this continuum of research and testing. Here’s why:

What the Government Doesn’t Want You to Know

How’s that for an inflammatory headline? Hey, you’ve probably heard it before: It doesn’t take a lot of Internet digging to find people who think the government has been suppressing the curative powers of cannabis. And in fact, they’re partly right.

“Even the pharma industry is handicapped by the federal government. For us to do any proper research with cannabis or cannabis-based medicines, there are incredible hoops to jump through – a year or more to get federal approval, then we have to use a product grown by the federal government, out of Mississippi, which is very different than the marijuana grown in the Colorado retail market,” says Tim Byers.

But according to everyone quoted in this article, it’s not that the government is withholding a lifesaving cancer medicine; it’s just that federal restrictions on the manufacture, handling and use of cannabis-based products leaves research stuck in the limbo of knowing the questions, knowing the techniques, but being barred from doing the research that could lead to answers.

Nicholas Foreman is as close as we currently get to a human clinical trial of cannabis in the context of cancer. “We are not prescribing a new cannabis product or anything like that,” he says. “We have patients with brain tumors who are moving here from other states due to the legality of cannabis and cannabis oils, and we’re looking at the quality of life in these children in a systematic way.”

In other words, Foreman, who is at the cutting edge of cannabis research, in the state that has become the poster child for cannabis, can’t test cannabis. Instead, he watches a system already in motion to see what happens. In fact, Foreman also hopes to explore dangerous, possible fungal contamination in cannabis oils used by his already immunocompromised pediatric patients…and to do so, he must have patients ship samples of their oil to a third-party laboratory that can do the testing and report the results, without ever handling the oil himself for fear that interacting with the oil might jeopardize federal funding for his research.

However, In Foreman’s opinion, it is specifically the impossibility of research with cannabis-based products that allows the misplaced hope we saw in the previous section. The thing is, whether or not marijuana, THC, cannabidiol or any other cannabis-based product works in palliative or curative settings, it would be really nice to know. The lack of research allows the conspiracy theory of government suppression, which allows people to believe that cannabis is a miracle cure for cancer…which leads to people mistakenly self-medicating with cannabis instead of seeking proven treatment that could cure their disease.

“I think we in Colorado are part of a movement that will inevitably tip public opinion so that Congress will have to take marijuana off of the list of drugs most tightly regulated,” Byers says. “As the movement grows and public opinion changes, we’ll get past some sort of a tipping point that allows us to more effectively explore the uses of cannabinoid-based drugs.”

Let’s revisit the score sheet. Smoking cannabis may increase cancer risk. Cannabis-based drugs are promising in the treatment of cancer symptoms. To the best of our knowledge, there is little hope that cannabis will treat cancer. And in all these cases, it would be darn nice to know more.

Topics: Research, Faculty, Cancer