By Brian D. Lawenda, M.D. 6 March 2016
There is much science about the medical efficacy of cannabis (marijuana) in oncology. Cannabis is a plant that is classified in the United States as a controlled substance, and by federal law, possessing cannabis in most U.S. states is illegal. That said,16 states and the District of Columbia permit its use for certain medical conditions with a physician’s prescription; however, doctors in these states may not legally do so without violating federal law and can lose their federal license to prescribe drugs and may also be prosecuted. Presently, three states—Colorado, Maine, and New Mexico—license producers and distributors of medical cannabis.
With that background established, let’s learn more as we delve into using cannabis in oncology.
What are the active compounds in cannabis?
More than 400 chemical compounds have been discovered within the cannabis plant. Of them, phytocannabinoids (or simply “cannabinoids”) are the main components that exert most of the plant’s pharmacological activity.
Further, there are more than 60 identified cannabinoids, but the four most well studied and characterized cannabinoids are delta-9-tetrahydrocannabinol (d-9-THC); cannabidiol (CBD); cannabinol (CBN); and tetrahudrocannabivarin (THCV).
Cannabinoid compounds are currently available as either synthesized chemicals or whole plant extracts, including Dronabinol (or “Marinol”), an FDA-approved synthetic THC pill; Nabilone (or “Cesamet”), also an FDA-approved synthetic THC pill; and Nabiximols (or “Sativex”); a not-yet-approved FDA natural tincture spray containing both THC and CBD.
What is the endocannabinoid system?
Some of the most exciting cannabinoid research involves the discovery of the body’s endocannabinoid system. Incredibly, our bodies make their own cannabinoid chemicals that interact and stimulate cannabinoid receptors on our cells. Studies continue to uncover the numerous functions of our endocannabinoid system, including:
- Anti-inflammatory activity
- Antioxidant activity
- Inhibiting tumor cell growth
- Inhibiting blood vessel growth to tumors
- Antiviral activity
- Involved in learning and nervous system plasticity
- Pain processing
- Neuroprotective effects
- Visual perception
- Immune system modulation
Routes of use of cannabis
Cannabis may be taken by mouth (i.e., baked products, butters, teas, liquid sprays tinctures, gum, beer, etc.) or may be inhaled through smoking or vaporizing.
One of the safest and most consistent ways to deliver a controllable dose of cannabis is through vaporization. It takes over one hour for Dronabinol (Marinol) to reach full systemic effect, compared to minutes for smoked or vaporized cannabis.
Safety of smoking cannabis
Research has found that habitual use of marijuana does not appear to lead to abnormalities in lung function, nor does it increase the risks of chronic obstructive lung disease (COPD) or either lung or upper airway cancer. It is associated with an increase in symptoms of chronic bronchitis; however, the symptoms go away upon discontinuation of use. That said, I still would prefer that my patients vaporize versus inhale smoke.
Uses of cannabis in oncology
As an integrative oncologist, I recommend using various methods for helping patients manage commonly encountered side effects and symptoms of cancer treatment and the cancer itself. Whenever possible, I start by suggesting non-pharmacologic therapies that have been shown to be effective, safe and are inexpensive. If the symptoms are moderate-to-severe or unlikely to be able to be controlled with non-pharmacologic approaches, this is when I will recommend using natural botanical products and/or pharmaceutical drugs. Five commonly experienced symptoms in cancer patients are:
- Diminished appetite (and associated weight loss)
- Sleeping difficulties
- Psychoemotional distress (i.e., anxiety, stress and depression)
Cannabis (as the whole plant compound) and the synthetic and extracted delta-9-tetrahydrocannabinol (d-9-THC) and cannabidiol (CBD) have all been shown to have significant efficacy in improving these five common symptoms in clinical trials. Your physician would need to prescribe five different drugs to (with the associated side effects and costs) to manage these symptoms…or, they could prescribe one drug that improves all five symptoms. If only one or two of these symptoms are causing significant problems, I typically don’t recommend using a cannabinoid since other pharmacologic options may be more effective in treating those individual symptoms. However, it is quite common to see patients with the majority of these symptoms manifesting at once (particularly in advanced stages of disease and treatment).
For these patients, I think it is very appropriate to recommend a cannabinoid or cannabis by itself or in combination with other pharmacologic (i.e., Megace for poor appetite, Zofran for nausea, etc.) and non-pharmacologic therapies (i.e., mind-body therapies, etc.). Recently reported data indicate that the combination of inhaled cannabis (via vaporization) with opioid pain medications leads to a synergistic effect, which decreases the amount of opioids needed for pain control. This synergistic action helps patients by reducing the side effects of higher dose requirements of opioids (i.e., sedation and nausea).
Is there any validity in using cannabis as an anti-cancer agent?
There are no quality clinical studies in humans that prove whether cannabis is able to improve cancer-specific outcomes such as survival, recurrence or progression. However, there are interesting and promising preclinical studies (using cancer cells or animal studies) that demonstrate the anticancer activity of cannabinoids. Excerpts from studies posted by the U.S. NCI PDQ: Cannabis and Cannabinoids include the following statements:
- “Studies in mice and rats have shown that cannabinoids may inhibit tumor growth by causing cell death, blocking cell growth, and blocking the development of blood vessels needed by tumors to grow.”
- “Laboratory and animal studies have shown that cannabinoids may be able to kill cancer cells while protecting normal cells.”
- “A study in mice showed that cannabinoids may protect against inflammation of the colon and may have potential in reducing the risk of colon cancer, and possibly in its treatment.”
- “A laboratory study of delta-9-THC in hepatocellular carcinoma (liver cancer) cells showed that it damaged or killed the cancer cells.
The same study of delta-9-THC in mouse models of liver cancer showed that it had antitumor effects. Delta-9-THC has been shown to cause these effects by acting on molecules that may also be found in non-small cell lung cancer cells and breast cancer cells.”
So, when asked by my patients if using cannabis or cannabinoids can help improve their cancer-specific outcomes I can only point to preclinical data on that question. We know that many seemingly amazing outcomes have been reported in preclinical studies, only to later have no effect in human studies. Therefore, it is important to recognize the limitations of projecting preclinical outcomes to human study outcomes. Safety of cannabinoids According to a 1995 review prepared for the World Health Organization, “There are no recorded cases of overdose fatalities attributed to cannabis, and the estimated lethal dose for humans extrapolated from animal studies is so high that it cannot be achieved by … users.”
In 2008, investigators at McGill University and the University of British Columbia reviewed 23 clinical investigations of medical cannabinoid drugs (typically oral THC or liquid cannabis extracts) and eight observational studies conducted between 1966 and 2007. Investigators “did not find a higher incidence rate of serious adverse events associated with medical cannabinoid use” compared to non-using controls over these four decades. Pharmacologic studies indicate that a human would need to eat 1,500 pounds of cannabis within 15 minutes to achieve lethal levels of cannabinoids.
That said, cannabinoids are active drugs with potential side effects and risks. According to Cancer.gov, potential side effects of cannabinoids may include:
- Rapid heartbeat • Low blood pressure
- Muscle relaxation • Bloodshot eyes
- Slowed digestion • Dizziness
- Depression • Hallucinations
Both cannabis and cannabinoids may be addictive. Symptoms of withdrawal from cannabinoids may include restlessness and hot flashes, and less common nausea and cramping.
Brian D. Lawenda, M.D., an integrative oncologist. He trained at Massachusetts General Hospital (Harvard Medical School) in radiation oncology and studied medical acupuncture at Stanford-UCLA (Helms Medical Institute). He is the founder of IntegrativeOncology-Essentials[dot]com.