What patients tell me anecdotally is that they will take two or three puffs, they will feel the effect immediately, and then they will stop. They will feel less anxiety, more relaxed, and in some cases experience pain relief or improved appetite.— Judith A. Paice, PhD, RN
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With reports about new marijuana dispensaries sprouting up as more states approve the legal use of medical marijuana, and patients and family members questioning how to get it, medical marijuana is a “topic you can’t escape,” noted Judith A. Paice, PhD, RN.1 Dr. Paice is Director of the Cancer Pain Program in the Division of Hematology-Oncology at Northwestern University, Feinberg School of Medicine, Chicago. She reviewed the pros and cons of medical marijuana for oncologists and other health-care professionals attending the 18th Annual Lynn Sage Breast Cancer Symposium and provided additional insight and information in an interview with The ASCO Post.
Marijuana, or cannabis, “has been with us through the millennia,” Dr. Paice noted. More than 5,000 years ago, it was widely used spiritually, recreationally, and medically, with some of those early medical uses the same as now—for the relief of pain, nausea and vomiting, and spasticity.
Three Types of Cannabinoids
There are three general types of cannabinoids:
Endocannabinoids are “like our own endogenous opioids,” Dr. Paice said. She pointed out that there is some correlation, but not causation, between the areas where these endogenous neurotransmitters are primarily located—the frontal cortex, basal ganglia, cerebellum, and hippocampus—and the effects and uses of marijuana.
“The frontal lobe is where we process pain and pleasure,” she explained; hence, the connection with euphoria and pain relief. The role of the basal ganglia in processing motor movements “may help us understand how marijuana works for spasticity,” Dr. Paice added. “And the hippocampus is the learning center, where we retain memory, for example. That is where the concern arises. Much of the literature about cognition and the long-term effects of marijuana is focused on adolescents, teenagers, and young adults, for whom the brain is still in development and may not be able to form memories.”
Phytocannabinoids are “what most of our patients are inhaling or ingesting and what is typically dispensed at the dispensaries,” Dr. Paice reported. There are 537 constituents in these phytocannabinoids, “so people who are inhaling or ingesting are getting a lot of other substances besides tetrahydrocannabinol (THC), which is known to lead to the more euphoric effect of phytocannabinoids, and cannabidiol (CBD), which is believed to provide the analgesic effect of the cannabinoids,” Dr. Paice noted.
The three primary types of phytocannabinoids are Cannabis indica, Cannabis sativa, and Cannabis ruderalis. There are beliefs about different concentrations of THC and CBD in each of these different strains, and “certainly the dispensaries make a lot of claims about the quality and the quantity of THC and CBD in their products,” Dr. Paice said.
“People have a misconception that what is in the dispensaries is somehow better than what is in the streets because it is medical. In fact, it is probably cleaner, but it is not necessarily different [chemically],” Dr. Paice said. The marijuana available today, either on the streets or in dispensaries, is much more potent than what some people may remember from the 1960s and 1970s, according to Dr. Paice.
Synthetic cannabinoids include older drugs such as dronabinol, which “was initially marketed to reduce nausea and vomiting,” Dr. Paice noted, but is “now being used primarily for wasting syndrome and is only labeled for AIDS-associated wasting.” Another older drug is nabilone (Cesamet), used for chemotherapy-induced nausea and vomiting. A newer agent is nabiximols (Sativex), an oral spray for neuropathic pain with equal measures of THC and CBD, Dr. Paice said. Nabiximols has been approved in Canada and numerous countries in the European Union for neuropathic pain control, but it has not been approved by the U.S. Food and Drug Administration, she added.
Three Routes of Administration
The three routes of administration for phytocannabinoids, the plant form and the most commonly used of the cannabinoids, are by inhaling (smoked or vaporized), ingesting as food, or using oils. “Inhaling is probably the safest of all of the routes. Despite our concerns about the other particulates, there are ways to inhale that are probably safer, like using vaporizers, and those can be easily found on the Web,” Dr. Paice said.
Inhalation is also the most common and most studied route. “Almost all of the studies have been conducted in inhaled or vaporized approaches to delivery,” Dr. Paice said. Inhaling produces high bioavailability with rapid and predictable onset and blood levels in 2 to 5 minutes, and marijuana that is inhaled is “easier to titrate,” Dr. Paice added.
“What patients tell me anecdotally is that they will take two or three puffs, they will feel the effect immediately, and then they will stop. They will feel less anxiety, more relaxed, and in some cases experience pain relief or improved appetite. Most users experience mild euphoria, relaxation, and some perceptual alterations and intensification of ordinary experiences. Some people, however, do experience some dysphoria, anxiety, and even paranoia, so we have to be aware of that,” Dr. Paice cautioned.
However, eating it is challenging, she continued. When marijuana is ingested, for example, in brownies, cookies, or sodas, “the bioavailability is much lower and the uptake is much delayed,” taking 2 to 6 hours, Dr. Paice noted. This also makes it more difficult to titrate to effect. “So what can happen—and this is being observed in the states where marijuana is approved for recreational use—is that people will eat a brownie, not feel anything; eat another brownie, still not feel anything; and then all of a sudden, they are experiencing severe changes in perception and may even hallucinate,” Dr. Paice said.
Studies are lacking on oils as the route of administration, but Dr. Paice noted that some people ingest the oils and some apply them topically. She also pointed out that producing the oils can be “quite a dangerous process. The process of taking the leaves and boiling them down or processing them to derive the oil leads to explosions. So when people are doing this illicitly, not under the rubric of a dispensary, it can lead to the same kind of fires we see with meth labs.”
In states where medical marijuana is legal, many of the dispensaries sell oils that have been legally processed in laboratories. These oils are not typically used by patients with cancer but by children with intractable seizures.
Certification, Not Prescription
An important point for clinicians to understand about medical marijuana, Dr. Paice stressed, is that “doctors are not prescribing. They are certifying a patient.” The reason it is so important to make that distinction is that “marijuana is still a Schedule I narcotic, like heroin. It is not allowed to be prescribed. So this is how the states have gotten around the federal law.” There have been efforts to change the federal law, but so far they have failed.
Each of the states where patients can legally obtain medical marijuana has its own list of approved medical conditions. Dr. Paice mentioned that in Illinois, where she practices, there are 35 such medical conditions and 3 criteria that must be met for certification. The physician must provide documentation to the state that a patient has one of those medical conditions, that in the physician’s judgment the patient might benefit from the use of medical marijuana, and that the physician has a sustained relationship with the patient.
“Patients have to complete a significant amount of paperwork. They have to get fingerprinted. They have to provide photos,” Dr. Paice said. To prevent patients from going to multiple dispensaries and getting multiple supplies of marijuana, patients in Illinois have to designate the dispensary that they are going to use. Then the patient gets a card from the state that allows him or her to pick up the drug from that dispensary.
It is up to patients to choose what they want at the dispensary. “The physician has no say on what they obtain,” Dr. Paice said, but can encourage safe use. “I would worry about the exposure to particulates in patients who are at risk for lung damage, like young people with lymphoma who are going to be treated with bleomycin, for example, which can cause lung damage. I can’t control what they do, but we can certainly encourage safety, which would include using a vaporizer.”
Limited Data on Antitumor Effects
In addition to the use of marijuana to ameliorate the side effects associated with cancer and its treatment, “some provocative laboratory data, both in the dish and in rodent models, suggest that marijuana may suppress tumor activity and the metastatic spread of tumors. So that is on the minds of many of our patients, who are beginning to look at cannabinoids as part of their anticancer therapy,” Dr. Paice said.
She cited one small study, which was neither randomized nor controlled, among nine patients with recurrent glioblastoma multiforme for whom treatment with surgery and radiotherapy had failed. “Treatment with THC decreased tumor growth and tumor progression, as assessed by magnetic resonance imaging and biomarker expression, in at least two of the nine patients studied,” according to a recent review article in JAMA Oncology on the use of medical marijuana in oncology.2 The article also presented several in vitro and animal studies as evidence suggesting that cannabis may be used as a potential chemotherapeutic treatment.
Adverse Effects
A 2014 article in The New England Journal of Medicine listed several adverse effects for the short-term use of marijuana, including impaired short-term memory and motor coordination, and for long-term use, including altered brain development, poor educational outcome, and cognitive impairment.3
“Certainly there is concern about short-term memory loss, again, given the effect of cannabinoids on the hippocampus,” Dr. Paice stated. “This seems to be of greater concern as teens, preteens, and young adults begin to use cannabinoids regularly and are heavy users. The data do suggest that this impairs long-term memory and may be associated with impaired IQ and possibly impaired cognition.”
There is no consensus on what constitutes long-term or heavy use, Dr. Paice noted. “Is that everyday use? If so, is that everyday use where you are just taking one or two puffs before you go to bed to relax? Or is it people who are smoking several joints every day, or the equivalent, for 10 years? I have known patients who have been recreational users and then need to come into the hospital for a stem cell transplant, for example. They can be in the hospital for 2 or 3 weeks, and they will get irritable. They experience something like withdrawal symptoms. In fact, that is where I sometimes use the synthetic product, kind of like a nicotine patch for the smoker who gets irritable when unable to smoke.”
Marijuana was also associated with increased emergency department visits but usually when used “in combination with other substances of abuse,” Dr. Paice noted. “There is an uptick in accidents reported” in states where marijuana is legal, she added, “but conversely, provocative data from large data sets show that in the states where marijuana is available medicinally or recreationally, we are seeing fewer opioid deaths.” Respiratory depression and death are very uncommon with marijuana, she pointed out.
“One of those paradoxical things,” Dr. Paice noted, is that while marijuana can be used to suppress nausea and vomiting, it can also cause hyperemesis, usually in people who smoke a lot. Since hyperemesis is aversive, she said, that could cause frequent smokers to cut back.
Low Lifetime Dependency Risk
Among the downsides associated with marijuana or chronic cannabinoid use, “there seems to be a lifetime dependency prevalence of about 9%,” Dr. Paice pointed out, citing the 2014 article in The New England Journal of Medicine.3 “That is certainly far lower than findings associated with many other substances that people use,” including estimates in the article ranging from 15% for alcohol and 17% for cocaine to 23% for heroin and 32% for nicotine.
Dr. Paice questioned whether that 9% figure for marijuana dependency incorporates irritability when people try to stop using marijuana or truly represents addiction. “There is great contradiction in the literature,” she said, adding that “Hazelton and other addiction centers report they are seeing increased rates of marijuana addiction, and Marijuana Anonymous fellowships have formed.” ■
Disclosure: Dr. Paice reported no potential conflicts of interest.
References
2. Wilkie G, Sakr B, Rizack T: Medical marijuana use in oncology: A review. JAMA Oncol 2:670-675, 2016.
