Oncology Takes on Cannabis

ABIGAIL JOHNSTON is a lawyer and a self-proclaimed rule follower. Nevertheless, every year at a listening session for patients at the San Antonio Breast Cancer Symposium, she asks officials from the Food and Drug Administration (FDA) what the agency is doing to ease restrictions on a substance classified as illegal by the federal government.

The substance is cannabis, and Johnston, who lives in Miami, has been taking it for more than four years to treat symptoms and side effects related to her breast cancer. She was originally diagnosed with stage II breast cancer at age 38 in March 2017. She began taking cannabis for chemotherapy-induced nausea after finding out she was allergic to the commonly used anti-nausea medication Zofran (ondansetron). Cannabis had been legalized in Florida for people with certain health conditions, including cancer, earlier that year.

In June 2017, Johnston learned her cancer was metastatic. Today, she uses cannabis oil to treat nausea related to the targeted therapies she takes, as well as to alleviate pain and allay her insomnia. Cannabis allows her to be present with her children, ages 6 and 8, in a way that opioids would not, she says. “Medical cannabis is the medicine that has helped me maintain my quality of life.”

Medical cannabis is now legal in 36 states and the District of Columbia, and these jurisdictions generally list cancer or related problems as qualifying conditions. The continued federal illegality of cannabis and the dizzying variety of its formulations, however, mean that taking cannabis is not like relying on more conventional medications. Medical cannabis laws vary by state, but patients seeking medical cannabis generally must be certified by a physician and register to get a medical cannabis card. They then may choose which formulation to purchase at a medical dispensary or, in certain states, grow a limited amount of cannabis themselves. Cannabis has also been legalized in 18 states for recreational use by adult members of the general population. Still, due to challenges in researching cannabis, there are sparse data from randomized trials on its efficacy in addressing cancer-related problems.

“We just need for there to be research so that the doctors feel more comfortable with it,” Johnston says. “Because if we could just do our peer-reviewed studies that they do for everything else they’re giving us, then we would know, ‘Is it safe or isn’t it?’ or ‘What are the parameters?’ and not have to have somebody guess. Because pretty much all of the recommendations that I’ve been given are an educated guess.”​

A Medicinal History

People have been growing cannabis plants for millennia. In the mid-1800s, physicians practicing Western medicine began using the botanical to treat various ailments, from seizures to mental disorders. But by the 1930s, the “dread marijuana”—as it was called in the 1936 film Reefer Madness—had been cast in the U.S. as a drug spread by immigrants that would turn young people to crime or insanity. In 1937, following various state legal prohibitions, the Marihuana Tax Act made it illegal on a federal level for people to possess or sell cannabis unless they had paid a tax. In 1970, the Controlled Substances Act classified cannabis as a Schedule I drug, a category of substance with “no currently accepted medical use in the United States, a lack of accepted safety for use under medical supervision and a high potential for abuse.”

“Cannabis’ Schedule I status makes it difficult to carry [out] clinical trials with the botanical. Researchers face considerable red tape, scarcity of study drug and lack of funding opportunities,” says Ilana Braun, a psychiatrist and chief of the Division of Adult Psychosocial Oncology at the Dana-Farber Cancer Institute in Boston.

Following the federal prohibition, some companies tried to treat cannabis like a more conventional medication, creating synthetic versions of its active components, called cannabinoids. The cannabis plant contains more than 80 biologically active components, the best known being delta-9­-tetrahydrocannabinol (THC) and cannabidiol (CBD), the FDA says. THC produces the “high” sensation associated with cannabis. The agency has approved various synthetic forms of THC for chemotherapy-induced nausea and vomiting.

Researchers wishing to study the more popular plant version of cannabis must get a Schedule I license and then get cannabis through the National Institute on Drug Abuse (NIDA). The agency’s mission is to monitor the causes and consequences of drug use and addiction, rather than to investigate potential benefits of the substances being studied, researchers say. The only approved source of cannabis for research has been the University of Mississippi, but researchers say the cannabis grown there is lower in THC than the cannabis on the market today. “The form and the components of it were not mirroring what people were using,” says Brooke Worster, a pain management and palliative medicine physician at Sidney Kimmel Cancer Center–Jefferson Health in Philadelphia. Worster runs a multidisciplinary clinic to help people with cancer navigate cannabis use. “It became almost meaningless to try to do clinical research that way in the United States,” she says.

Nevertheless, some data on cancer and cannabis are available. A 2017 report by the National Academies of Sciences, Engineering and Medicine reviewed what evidence existed from randomized trials on the efficacy of cannabis and synthetic cannabinoids in treating various symptoms. The study’s authors found “conclusive or substantial evidence” that cannabis can help treat chronic pain in adults and that oral cannabinoids can treat chemotherapy-induced nausea and vomiting. Since publication of the original studies comparing oral cannabinoids to available anti-nausea treatments, more effective anti-nausea drugs have been approved, but cannabinoids are still seen as a useful alternative or addition to anti-nausea medications for some patients.

“I believe that cannabis is really useful for symptom management in people living with and beyond cancer,” says Donald Abrams, an oncologist at the University of California, San Francisco, Osher Center for Integrative Medicine.

There is less evidence for whether cannabis can improve appetite and increase weight in cancer patients, says Worster. People also use cannabis to treat anxiety, depression and insomnia, she says, but the evidence in these areas is unclear, and there is concern that it could even worsen symptoms of depression. “There’s a fine line because it’s probably problematic in people that have known, more significant depression,” she says.​​​​

Who Is Using Cannabis?

For many years, little data existed on how commonly cancer patients use cannabis. For a 2017 Cancer paper, Steven Pergam, an infectious disease specialist at the Fred Hutchinson Cancer Research Center and the Seattle Cancer Care Alliance (SCCA), and his colleagues surveyed their patients on cannabis use. Out of 926 patients who took the survey, 24% said they had used cannabis in the past year, and 21% said they had taken it in the past month. The most common reasons for taking cannabis were pain, nausea and stress.

An analysis of data from the National Survey on Drug Use and Health, published September 15, 2021, in Cancer, shows a lower overall rate of cannabis use in the U.S. population of cancer patients, with nearly 10% of those reporting a cancer diagnosis in the past year also saying they had used cannabis in the past year. The analysis was led by Matthew Cousins, chief resident in radiation oncology at the University of Michigan in Ann Arbor, who looked at data gathered between 2015 and 2019. Nearly 16% of people without cancer reported cannabis use in the past year, according to the survey data, although cancer was associated with an increased rate of cannabis use in people between the ages of 35 and 49.

To try to learn more about who is using cannabis, the National Cancer Institute (NCI) in 2020 issued a call for proposals from NCI-designated cancer centers to do more surveys of cannabis use among patients.

Data show strong interest in cannabis use among people with cancer. Around three-quarters of all patients surveyed at SCCA said they wanted information about cannabis from their cancer doctors and nurses, although fewer than 15% reported receiving this information. At the same time, oncologists feel unprepared to talk about cannabis with their patients. A 2018 study published by Braun and her colleagues in the Journal of Clinical Oncology found that 80% of 237 medical oncologists surveyed reported conducting discussions of cannabis with their patients, while just 30% of the oncologists said they felt sufficiently informed to make cannabis-related recommendations.

For patients, interactions with doctors about cannabis can come across as dismissive or insufficiently helpful. In a study published in the Jan. 1, 2021, issue of Cancer, Braun and her colleagues interviewed 24 people with cancer recruited at medical cannabis dispensaries in various states. People generally reported getting their medical cannabis certifications through “brief, perfunctory” meetings with medical professionals they didn’t know. When they told their regular doctors about their cannabis use, the doctors often did not have much advice for them.

Alexandra Glorioso of Tallahassee, Florida, who was diagnosed with breast cancer in 2018, echoes the study findings, calling her first visit with a doctor to get her cannabis certification a “joke visit.” Glorioso, who is the founder of Barred Owl Press, a new media company dedicated to educating and empowering patients, uses cannabis for pain, nausea and her mental health. “They just asked me what kind of marijuana I like to smoke and why I’m there. They were like, ‘We have to technically give you a physical, but we don’t really know what to do.’” The visit cost $250, plus a $75 fee she paid to the state. She must pay to renew her card each year.

For Johnston, who had never used cannabis prior to her cancer diagnosis, the learning curve was steep. When she was first diagnosed, she was being treated in a religious hospital system, and her doctor was required to tell her that taking cannabis was wrong. She sought out a doctor outside her health care system to get certified for medical cannabis.

“The first doctor I saw said, ‘Start at 5 milligrams and take it until you feel weird.’ … I felt very adrift, quite frankly,” she says. She joined a Facebook group for people with breast cancer who used cannabis and found a nurse who could advise her via telehealth based on her years of anecdotal experience with cannabis. Johnston later moved to Miami and has found her new medical team to be more supportive of her cannabis use.

The legalization of cannabis for medical or recreational use in many states has added pressure for researchers to have answers to patients’ questions about cannabis, says Cousins. “We’ve had state-level legislation, which has really gotten far ahead of the federal rules at this point. … Researchers are really quite far behind and are struggling to catch up with the needs of society.”

Research Shows Signs of Life

The history of cannabis research in cancer patients has been cause for frustration, but there are signs that new research could be on the horizon.

On May 14, 2021, the Drug Enforcement Agency (DEA) announced that it is “nearing the end of its review” of applications from institutions other than the University of Mississippi that would like to grow cannabis for research purposes. These growers would be able to supply cannabis for research to DEA-licensed researchers.

In the meantime, researchers have been finding new ways to study cannabis in people with cancer. In 2018, the U.S. Farm Bill removed hemp—classified as cannabis containing only a very low level of THC—from the definition of marijuana in the Controlled Substances Act. This change led to the proliferation of CBD for sale at gas stations and similar outlets, but it also allowed researchers to study the substance more easily.

When Marisa Weiss, director of breast radiation oncology and breast health outreach at Lankenau Medical Center in Wynnewood, Pennsylvania, first started getting questions about cannabis, she would tell her patients to seek help from a list of people who knew more about it than she did. Weiss is also founder and chief medical officer of BreastCancer.org, a nonprofit organization that provides information and support for people with breast cancer.

“Finally, I had one patient, this really smart woman, who said, ‘Marisa, that’s not OK. That’s not good enough. I expect more from you. Maybe someone else can get away with saying that, but we trust you, you’re a leader in the field. We need you to help us understand cannabis medicine,’” Weiss says. She obtained certification in the states of Pennsylvania and New York to qualify patients for medical cannabis, provided information on BreastCancer.org and began working to start a study on cannabis to build a body of knowledge on the topic.

In May 2020, Weiss launched a randomized, double-blind, controlled clinical trial through her laboratory, Socanna, in collaboration with Lankenau. Socanna is dedicated to advancing scientific knowledge of cannabis. In the study, people with nonmetastatic ovarian, colorectal, uterine or breast cancer who developed chemotherapy-induced peripheral neuropathy are randomly assigned to take either CBD gel capsules derived from hemp or placebo gel capsules. Braun is launching a randomized, double-blind, controlled trial testing whether pharmaceutical-grade CBD can improve symptoms of anxiety prior to CT scans, also called scanxiety, in adults with advanced breast cancer.

Other researchers have had success partnering with state medical cannabis programs and dispensaries to study cannabis. Dylan Zylla, a medical oncologist and hematologist at Park Nicollet in St. Louis Park, Minnesota, published results on June 4, 2021, in Sup​portive Care in Cancer of a randomized trial of cannabis products for treating pain in people with stage IV cancers taking opioids. Zylla and his colleagues did not need to get a DEA license or distribute cannabis to the patients. Rather, cannabis was supplied at no cost by dispensaries, which had lists of which patients were allowed to come and get cannabis products and at which times. The study was not large enough to come to firm conclusions about the impact of cannabis on pain, Zylla says, but it demonstrated that this format for clinical trials has potential.

In Pennsylvania, Worster helped craft Chapter 20 of the 2016 Medical Marijuana Act, allowing academic medical centers to partner with medical cannabis dispensaries to do research. Worster and her colleagues are currently enrolling people with pain who are on opioids, including cancer patients, in a study of cannabis oils provided by Ethos dispensaries across Pennsylvania. The researchers will test whether cannabis reduces opioid use. One group of patients who are not certified users of medical cannabis agrees to continue not taking cannabis. Patients who wish to take cannabis agree to use only cannabis provided by the dispensary and are randomly assigned to receive cannabis oils of varying formulations to use under the tongue. The formulation of cannabis provided varies each month for three months, with the patients blinded to the composition of each oil. For the fourth month of the study, the patients choose which of the oils they want to use. All participants in the study fill out surveys on their pain, as well as their opioid and cannabis use.

In the future, many researchers hope that easing restrictions on cannabis research will allow more rigorous investigation, so that doctors can finally answer patients’ questions with solid data. “I think the scientist in me says, ‘I’d like to see randomized, placebo-controlled trials that would assess how much of these are beneficial and to do comparisons of cannabis in addition to drugs that we know work for specific complications that they are using it for or in combination with those drugs to see if they’re beneficial,’” says Pergam.

However, Abrams, who attempted and failed to accrue patients to trials of cannabis for cancer-related symptoms over the course of his career, does not think the “pharmaceuticalization of marijuana” will ever work. People respond differently to cannabis, and today, there is an “embarrassment of riches” in the forms of cannabis available that will make standardization difficult. “This has been a therapeutic botanical that’s been used by people for thousands of years,” he says.

Studies on cannabis will never be done “exactly like the way that we do trials for drugs that come through pharma,” says Worster. “It’s got to be its own unique thing because it is its own unique thing.”

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