This is a completely non-political blog entry on the science of the medical efficacy of Cannabis (marijuana) in oncology. Cannabis is plant that is classified in the U.S. as a controlled substance with an “increased potential for abuse and no known medical use” (Schedule 1). By federal law, possessing Cannabis, is illegal in the U.S. Although U.S. federal law prohibits the use of Cannabis, 16 states and the District of Columbia permit its use for certain medical conditions with a physicians’ prescription. That said, doctors in these states may not legally do so without violating federal law and can lose their federal license to prescribe drugs and be prosecuted. Presently, 3 states (Colorado, Maine, and New Mexico) license producers and distributors of medical cannabis. Now that I have established that, let’s learn more.
What are the active compounds in Cannabis?
There are over 400 chemical compounds that have been discovered within the Cannabis plant. The phytocannabinoids (or simply,” cannabinoids”) are the main chemical components that exert most of the pharmacological activity of the plant. There are more than 60 identified cannabinoids, but the 4 most well-studied and characterized cannabinoids are delta-9-tetrahydrocannabinol (d-9-THC), cannabidiol (CBD), cannabinol (CBN), and tetrahydrocannabivarin (THCV).
Cannabinoid compounds are currently available as either synthesized chemicals or whole plant extracts, including:
- Dronabinol (Marinol): U.S. FDA-approved, synthetic THC pill
- Nabilone (Cesamet): U.S. FDA-approved, synthetic THC pill
- Nabiximols (Sativex): not yet approved by the U.S. FDA (approved in Canada and in the UK), natural tincture spray containing both THC and CBD
- Here’s a great article on the development of Sativex. (Mother Jones)
- Review articleon the differences between Marinol and Cannabis (NORML.ORG):
- Summary of key points: 1) Marinol lacks several of the therapeutic compounds available in Cannabis, 2) Marinol is more psychoactive than Cannabis, 3) Cannabis vaporization offers advantages over orally administered THC, 4) Marinol is more expensive than Cannabis, 5) Patients prefer Cannabis to Marinol
What is the endocannabinoid system?
Perhaps the most exciting area of cannaboid research involves the discovery of the body’s endocannabinoid system. Incredibly, our bodies make their own cannabinoid chemicals which interact and stimulate cannibinoid receptors on our cells. Studies continue to uncover the numerous functions of our endocannabinoid system, including:
- anti-inflammatory activity: anticancer
- antioxidant activity: anticancer
- inhibiting tumor cell growth (apoptosis): anticancer
- inhibiting blood vessel growth to tumors (anti-angiogenesis): anticancer
- antiviral activity
- involved in learning and nervous system plasticity
- pain processing
- neuroprotective effects
- visual perception
- immune system modulation: anticancer
Routes of use of Cannabis:
Cannabis may be taken by mouth (i.e. baked products, butters, teas, liquid sprays and tinctures, gum, beer, etc.) or may be inhaled, through smoking or vaporizing (read my blog entry on vaporization). One of the most safe and consistent methods of obtaining a controllable dose of active drug when using 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.
Is Smoking Marijuana Safe? A new research study has found that habitual use of marijuana DOES NOT appear to lead to abnormalities in lung function, nor does it increase the risks of COPD (chronic obstructive lung disease) 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 the use of 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.
5 commonly experienced symptoms in cancer patients are:
- nausea
- diminished appetite (and associated weight loss)
- pain
- 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 5 common symptoms in clinical trials.
Your physician would need to prescribe 5 different drugs to (with the associated side effects and costs) to manage these symptoms…or you they can prescribe one drug which improves all 5 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. Unfortunately, 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 affect, 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 the use of Cannabis as an anticancer agent?
There are no quality clinical studies in humans that have been done for us to know if Cannabis or any of the cannabinoids are able to improve cancer-specific outcomes (i.e. survival, recurrence, progression).
There are interesting and promising preclinical studies (using cancer cells or animal studies) that demonstrate the anticancer activity of cannabinoids:
(from the U.S. NCI PDQ: Cannabis and Cannabinoids):
- “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.”
- Glioma and other cancer cell types:
- “In addition to cannabinoids’ ability to moderate glioma cells, separate studies demonstrate that cannabinoids and endocannabinoids can also inhibit the proliferation of other various cancer cell lines, including breast carcinoma,[11-15] prostate carcinoma,[16-18] colorectal carcinoma,[19] gastric adenocarcinoma,[20] skin carcinoma,[21] leukemia cells,[22-23]neuroblastoma,[24] lung carcinoma,[25-26]uterus carcinoma,[27] thyroid epithelioma,[28] pancreatic adenocarcinoma,[29-30], cervical carcinoma,[31]oral cancer,[32] biliary tract cancer (cholangiocarcinoma)[33] and lymphoma.[34-35]“
- Colon cancer:
- “Although cannabidiol has been shown to kill glioma cells, to inhibit cancer cell invasion and to reduce the growth of breast carcinoma and lung metastases in rodents, its effect on colon carcinogenesis has not been evaluated to date. This is an important omission, since colon cancer affects millions of individuals in Western countries. In the present study, we have shown that cannabidiol exerts (1) protective effects in an experimental model of colon cancer and (2) antiproliferative actions in colorectal carcinoma cells.”
- Breast cancer:
- “The administration of THC reduces the tumor growth of metastatic breast cancer and “might constitute a new therapeutic tool for the treatment” of cancerous tumors, according to preclinical data published online in the journal Molecular Cancer.”
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.
Here’s a fantastic 50-minute documentary (What if Cannabis Cured Cancer). Dr. Andrew Weil writes “What If Cannabis Cured Cancer summarizes the remarkable research findings of recent years about the cancer-protective effects of novel compounds in marijuana. Most medical doctors are not aware of this information and its implications for prevention and treatment. This documentary presents compelling evidence that our current policy on cannabis is counterproductive and foolish. An excellent film.”
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.
Potential side effects of cannabinoids may include (from the NCI PDQ):
- Rapid beating of the heart.
- Low blood pressure.
- Muscle relaxation.
- Bloodshot eyes.
- Slowed digestion and movement of food by the stomach and intestines.
- Dizziness.
- Depression.
- Hallucinations.
- Paranoia.
Both Cannabis and cannabinoids may be addictive. Symptoms of withdrawal from cannabinoids may include (from the NCI PDQ):
- Restlessness.
- Hot flashes.
- Nausea and cramping (rarely occur).
References on safety and risks:
- Here is an up to date reference on these side effects and risks for Dronabinol (Marinol).
- What is the risk of Cannabis use on developing cancer?
Clinical Trials of Cannabis or Cannabinoids in Cancer
In preparing this blog entry, a search of the U.S. NCI Clinical Trials website (with search keywords: cannabis, cannabinoid, THC) identified 5 registered phase 2 and phase 3 clinical trials that are currently active or approved for studying the effects of these agents in patients with cancer. Unfortunately, none of these studies involves the use of the whole plant (Cannabis).
Clearing the Smoke: The Science of Cannabis
MontanaPBS’s new documentary, Clearing the Smoke, reveals how cannabis acts on the brain and in the body to treat nausea, pain, epilepsy and potentially even cancer. Extensive interviews with patients, doctors, researchers and skeptics detail the promises and the limitations of medicinal cannabis. (57 minutes. February 2011)
The Science of Medical Cannabis: A Conversation with Donald Abrams, M.D.
Dr Sanjay Gupta: Why I Changed My Mind On Weed (CNN)
Dr. Sanjay Gupta says we have been “systematically misled” on marijuana. Watch the video.
Marijuana Gateway to Health: How Cannabis Protects Us from Cancer and Alzheimer’s Disease
Clint Werner is a recognized expert in the science, history and politics of Cannabis. This excellent book is a review on everything you ever wanted to know on this subject. It is up to date, scientific and factual, which appealed to me over a biased rant. (published: September 2011).
I recently found this well-written article reviewing the commonly asked questions about whether cannabis has anti-cancer efficacy, safety issues, conspiracy theories and legalization.
