Concurrent Use of Cannabis May Reduce Efficacy of Immune Checkpoint Inhibitors
With an increasing number of states legalizing medicinal and/or recreational marijuana and related products, more and more people with cancer are using these products. As of this writing, the US Drug Enforcement Agency lists marijuana and its cannabinoids as a Schedule I controlled substance that cannot be sold, prescribed, or possessed under federal law. 1 Rates of cannabis use among cancer patients varies in studies, likely due to its current federal designation, and ranges from 24% (current use) to more than 40% (ever use).
Patients should be encouraged to report use of cannabis and any other complementary and alternative medicine products so potential interactions with cancer therapy can be identified. This is especially important with the immune checkpoint inhibitors, including CTLA-4 antibodies (ipilimumab [Yervoy]), PD-1 inhibitors (eg, nivolumab [Opdivo]) and PDL-1 inhibitors (eg, durvalumab [Imfinzi]).
Use of immune checkpoint inhibitors in cancer is continually increasing, both as single agent therapy and in combination with cytotoxic chemotherapy (eg, carboplatin [Paraplatin]; pemetrexed [Alimta]) or targeted agents (tyrosine kinase inhibitors such as axitinib [Inlyta] and others). Multiple analyses have shown that concurrent use of cannabis products with immune checkpoint inhibitors is associated with reduced treatment efficacy.
In a retrospective, single-center review of 104 patients with advanced cancer, overall survival was reduced in the 27% of patients who used cannabis concurrently with their immune checkpoint inhibitor compared with those who did not use cannabis (16 vs 40 months). 2 This trial included prescription cannabinoids such as dronabinol (Marinol) as well as marijuana use.
Another prospective, observational study, this one with 102 patients beginning immune checkpoint inhibitors for metastatic cancer found lower rates of clinical benefit (complete response + partial response + stable disease; 39% vs 59%), shorter time to tumor progression (3.4 vs 13.1 months), and shorter overall survival (6.4 vs 28.5 months) in the 34 patients who also used cannabis. 3 This analysis noted a trend toward reduced adverse effects of immunotherapy, but this was not statistically significant.
The overall clinical literature is limited by nonrandomized, observational study design; however, these observations suggest that concurrent use of cannabis with immune checkpoint inhibitors should be discouraged until more information is available.
The exact mechanism for this effect is unclear, although it appears that cannabinoids may have some role in immune system regulation and have anti-inflammatory activity that may dampen the response to immune checkpoint inhibitors.
Patient information regarding the general use of cannabis in cancer is available from the American Cancer Society (“Marijuana and Cancer”) and the National Cancer Institute (“Cannabis and Cannabinoids (PDQ®) – Patient Version”).
Cancer Patients Get Little Guidance From Doctors On Using Medical Marijuana
Kate Murphy felt frustrated by a lack of advice from doctors on how to use medical marijuana to mitigate side effects from her cancer treatment.
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Even three queasy pregnancies didn’t prepare Kate Murphy for the nonstop nausea that often comes with chemotherapy.
In the early months of 2016, the Lexington, Mass., mother tried everything the doctors and nurses suggested. “But for the most part I felt nauseous 24/7,” she said.
Murphy, then 49 and fighting breast cancer, dropped 15 pounds from her already slim frame in just two months. Then, she remembered what a fellow cancer patient had advised while she was waiting for her first dose of chemo: “Make sure you get some medical marijuana.”
Scientific research, mostly in animals, supports the idea that cannabis can effectively treat the nausea of cancer therapy, in addition to some types of cancer-related pain, according to the National Cancer Institute’s cannabis information page.
And roughly a quarter of cancer patients use cannabis in Washington state, where both medical and recreational marijuana is legal, a study from September found.
In Massachusetts, medical marijuana has been legal for six years, but it’s still a challenge for cancer patients to get a state-issued medical marijuana ID card, or then figure out what kind of cannabis to use.
“I was flabbergasted that there was no real resource A, B and C, and ‘here’s how you do it,’ ” Murphy said. “What I liken it to is, ‘you need chemo, now go figure it out.’ “
This story from WBUR’s CommonHealth is part of an ongoing series called “This Moment In Cancer.” Here is a selection of other stories from the project:
Like most patients, Murphy’s first step was to ask her oncologist. Murphy said she loved her doctor and care team at Mount Auburn Hospital in Cambridge, but they had no advice to offer on medical marijuana.
“They said ‘yes, you can look into it,’ ” she said. “But I felt sad because you’re so lost and you’re so sick and this is so not your area of expertise, that it was very upsetting to me to not get direction one way or the other.”
Only about 1 percent of Massachusetts’ 25,000 doctors are registered with the state and allowed to legally prescribe marijuana. And only a fraction of those know much about cancer care.
Last June, the Massachusetts Medical Society approved a new online curriculum for medical marijuana. Six months later, only 27 medical professionals have taken the section on cancer care and cannabis. Both the Dana-Farber Cancer Institute and the Massachusetts General Hospital Cancer Center said they had no experts on staff to speak with us for this report.
Murphy eventually found her way to Dr. Jordan Tishler, who runs medical cannabis clinics in Cambridge and Brookline, called inhaleMD.
Tishler, a former emergency room physician and music producer, said he treats cannabis like any other therapy, meeting with new patients for an extended conversation and follow-ups. But some cannabis prescribers, he said, just want to sign the state paperwork and move on.
“By and large, physicians are simply saying, ‘yes, you can have it,’ and then stopping the conversation there,” he said.
Tischler explained that medical centers — particularly those that take federal funding — are in a tight spot because federal law still classifies cannabis as an illegal drug, despite its legalization for medical purposes, at a minimum, in 30 states and the District of Columbia.
“Most of those institutions are prohibited and/or afraid of the prohibitions from the federal government, so have opted not to pursue this within their domain,” Tischler said. He set up his private clinic so he could operate outside of those systems, though he said he receives referrals from all the major hospitals.
In early January, Attorney General Jeff Sessions told the nation’s U.S. attorneys to resume aggressively pursuing marijuana growers and distributors, even in states where marijuana has been legalized. It’s not clear yet what that will mean for Massachusetts’ medical marijuana system, but a few days later, Massachusetts U.S. Attorney Andrew Lelling said he cannot and will not rule out prosecuting state-sanctioned marijuana businesses.
As it currently stands, authorized doctors like Tishler have to fill out an online form with the state, which the patient then submits with a $50 check to request a license. Tishler said the process used to take several weeks, but now the state usually issues a medical card within three or four days of receiving a request.
Then, the patient has to take that license to one of the state-approved medical marijuana dispensaries, which offer a wide array of products containing cannabis.
New England Treatment Access in Brookline, Mass., is located in a former branch of Brookline Bank. Jesse Costa/WBUR hide caption
New England Treatment Access in Brookline, Mass., is located in a former branch of Brookline Bank.
New England Treatment Access, or NETA, whose Brookline dispensary is housed in an old bank building, sells 130 products. Garden Remedies, whose dispensary is in Newton about a block from a Whole Foods, sells 50 items, including bath bombs, lip balm and marijuana-infused honey they make themselves in their cultivation facility.
Murphy said she would have been overwhelmed by those choices if she hadn’t had a doctor like Tishler advising her on what to take. Tishler said he tells cancer patients, for example, that they should avoid using novelty items like bath bombs and creams. They may be fun, but they won’t help with nausea or pain, he says.
Murphy didn’t like the idea of edibles. She had young children at home and was anxious they might find a brownie too tempting to pass up.
Tishler warned his patients against getting advice on care either from the Internet — which he said is loaded with misinformation — or from the counter folks at the dispensaries, who are trained in their products but are not legally allowed to give out medical advice.
“They’re doing the best they can, but fundamentally, they’re salespeople,” he said. “Their level of training, I often say, is about the level of a Starbucks barista. So, I tell patients, ‘look, if you wouldn’t ask your coffee guy about your health, probably you shouldn’t ask these guys, either.’ “
Dispensing Experimental Wisdom
Dr. Karen Munkacy, president and CEO of Garden Remedies, said her staff generally recommends that someone with nausea use a vape pen, to get a quick effect from the cannabis, and then, if they need something longer-lasting, take an edible.
“Inhalation medical marijuana works within a few minutes, and so, now their nausea and vomiting is under control,” she said. “If they want to get a good night’s sleep they’re going to need to get something that they ingest because it’s going to last longer. They won’t wake up vomiting in the middle of the night.”
Munkacy started her company after her own bout with chemo-induced nausea. She was treated for breast cancer a decade ago in New Jersey, where medical marijuana was illegal.
“It was months of feeling a thousand times worse than any flu I’ve ever had,” said Munkacy, who at the time was an anesthesiologist with a 2-year-old son. “Before [medical cannabis] became legal, people would have to choose between breaking the law and suffering terribly.”
Convinced that medical marijuana could help other people avoid her misery, Munkacy worked to help get legalized medical marijuana on the ballot in Massachusetts in 2012, and said she is now committed to educating patients who come to her dispensary.
“Our goal is that when patients leave, they’ve learned everything they need to know,” she said.
Cannabis is generally very safe, Tishler said, as long as patients buy their medical marijuana from a dispensary, because state requirements ensure a safe, consistent product. There is no lethal dose, and the worst side effect for most of his patients, he said, is an unwanted feeling of getting high when they’ve taken too much.
Norton Arbelaez, director of government affairs for NETA, which also has a dispensary in Northampton, said that safety profile means patients can afford to be a little imprecise about what kind of marijuana they use and how much they get.
“There is some room here for the patient themselves to experiment and see what’s right for them,” he said.
In the end, that’s what Murphy did. She experimented. She tried a few joints and smoked a few times with a pipe.
She had already spent $700 paying Dr. Tishler, getting her $50 state license and buying the cannabis, so she didn’t want to invest more in the vaporizer Dr. Tishler recommended.
But even just those few weeks of occasional smoking made a big difference, Murphy said.
“It made me feel like I had an appetite for the first time in probably six months,” she said. “Instead of lying around thinking about how sick I felt all the time — which was not my personality, which was very upsetting to my whole family — I was up and cooking, which was not anything I had done since I hadn’t felt well.”
Murphy, who is now cancer-free, hasn’t smoked since her treatments ended in the summer of 2016. She still wishes patients didn’t have to work so hard to get the information they need about medical marijuana.
Younger Patients and Cannabis
The situation for children and teens with cancer is a little different than for adults, according to Prasanna Ananth, a pediatric oncologist at Yale Cancer Center. Ananth published a study in early December showing that an overwhelming majority of pediatric oncologists, nurses and other health care professionals in Massachusetts, Illinois and Washington state were willing to consider medical marijuana for children with cancer — particularly for those with advanced illness.
There are decades of research showing the potential dangers of marijuana for children and teenagers, but almost none into its possible benefits for young cancer patients, she said.
“Our calculus shifts when we’re talking about children facing serious, life-threatening illness,” Ananth said. “Health care providers must weigh their desire to provide compassionate care for their patients against limited scientific evidence to support use of medical marijuana by children.”
In her survey, nearly 1 in 3 pediatric oncology experts said they had been asked about medical marijuana by at least one patient.
Ananth said she would prefer to talk with her patients about their marijuana use than not know that they’re using it.
“Especially for the purpose of knowing what my patients are on and what the medical marijuana might interact with, it is important for us to maintain open lines of communication,” she said.
With Legal Pot Shops, Medical Use May See Boost
It’s not clear how Massachusetts’ medical marijuana system will change later this year when recreational marijuana sales are set to begin. Patients will pay 20 percent less than recreational users because they won’t have to pay taxes on their cannabis.
But Munkacy said she believes many more people will start using cannabis for their medical problems once recreational use becomes legal.
They may not have wanted to give their name to the state for a license, but the reduced restrictions and added legitimacy of legal marijuana will give them the push they need to start using it, Munkacy explained.
“I’m thinking there’s going to be a lot of people who will no longer have to buy their medicine on the black market.”
The first version of this story appeared on WBUR’s CommonHealth. Karen Weintraub spent 20 years in newsrooms before becoming a freelance writer in January 2010. She contributes to CommonHealth.
Aiming High: Israeli Scientist Attempts To Kill Cancer Cells With Cannabis
These days, cannabis is about a lot more than getting high; a new Israeli study supports the idea that cannabis could be used to kill cancer cells.
Biologist Dr. David Meiri of the Technion-Israel Institute of Technology is conducting cutting-edge research showing that combinations of different compounds in cannabis can be extremely effective in destroying specific cancer cells.
Cancer cells. Eloxx
According to the World Health Organization, cancer is the second leading cause of death globally, and resulted in 8.8 million deaths in 2015. The primary medical treatment, chemotherapy, can have unpleasant side effects such as hair loss and lethargy. But an Israeli researcher claims that cannabis could offer an alternative to chemotherapy, without the harmful side effects.
The idea that cannabis could cure cancer is not new. However, much of the evidence is anecdotal, and scientific research conducted in the past has not precisely identified which cannabis compounds kill which cancer cells, and why. “We realized that there is a vacuum,” Meiri tells NoCamels. “People don’t know and understand the strains [of cannabis] enough.”
Along with his team of 30 researchers in the Laboratory of Cancer Biology and Cannabinoid Research, Meiri is working to remedy this. His solution is to identify the exact chemical composition of different strains of cannabis. By systematically applying these strains to different cancer cell samples, he has been able to determine which strains of cannabis kill specific cancer cells.
“Bringing back the ability of the cancer to commit suicide”
The mechanism is similar to chemotherapy. One of the defining characteristics of cancer cells is their inability to ‘die’ like normal cells. The natural process of self-destruction, termed apoptosis, is not occurring; as a result, the cancer cells spread and invade other parts of the body. What cannabis has the potential to do, according to Meiri, is “like bringing back the ability of the cancer to commit suicide.”
Meiri is optimistic about the potency of the drug. “We’re talking about very low dosages,” he tells NoCamels, “milligrams of extract that are killing the cells.” This is a similar dosage to what is currently administered for chemotherapy, and is small enough to not kill normal, healthy cells. It means that cannabis could be a viable drug to be prescribed for cancer in the future.
Cannabis is the name of the plant from which marijuana is derived. The plant itself is made up of different molecular families, such as cannabinoids, terpenes, and flavonoids. Discussions on cannabis often focus on the two most prominent cannabinoids: THC and Cannabidiol (CBD). THC is a psychoactive compound that gives the ‘high’ commonly associated with marijuana usage, while CBD is non-psychoactive. Both have been proven to have a wide range of medicinal benefits, from reducing epileptic seizures, to minimizing violence and anxiety in autistic patients.
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Different strains of cannabis have different combinations of these compounds, and can thus have vastly different effects on the body.
Already, cannabis is being used to reduce the side effects of other cancer treatments; studies have found that it eliminates the vomiting and nausea caused by chemotherapy. While observing this, scientists began to realize that cannabis was actively reducing or stopping the spread of cancer cells themselves.
This revelation inspired Meiri to gather more data. Using sophisticated machinery, he has managed to identify the exact composition of compounds such as cannabinoids and terpenes in every single strain grown in Israel.
It’s valuable information. “I think that the depth of looking in the compounds is something that nobody else is doing,” says Meiri. “If something is working, or something is not working, we can see from the bottom to the top what is the difference [in the chemical composition].” In contrast, most of the current research is focusing on only a few cannabinoids.
Child Patient Female Doctor. Courtesy
Long way from a cure
Although Meiri’s research has exciting potential in the battle against cancer, we still have a long way to go before we find an all-encompassing cure. The lab’s research is currently limited to samples of cancer cells in laboratories; the human body is far more complex.
Meiri is wary about inflating the potential of cannabis, and stresses the importance of approaching it with a critical, scientific mindset. “I don’t think people should use cannabis as a treatment to cancer before we know how to treat them well,” he emphasizes. “If it’s their last chance and nothing is working anymore… for these people, they might try cannabis. But not as a first battle.”
He is realistic about the limits of his research, yet carefully optimistic: “Cannabis won’t solve all types of cancer, but if we can find five, six, or seven types of cancer that cannabis can help, it’s huge, it’s amazing.”