Photo credit: ___ariel___
There are some very passionate supporters of weed out there. It can cure cancer and relieve pain while freeing your mind. You could be lead to believe that it is a cure all for nearly everything. Its understandable that people are passionate about the topic when they do have very good and valid points in the face of a government that just doesn’t seem to get it. The voice of support has to become louder and more impactful as the frustration mounts. Believe me, the government gets it, but lobby groups have more power over rational discussion in American politics. And cannabis certainly has a place in medicine, it just may not quite live up to the hyperbole…but it might. We should have had a better idea of its medicinal value years ago, had those efforts not been hampered by the legal status of cannabis over the last century. In this article, I’ll explore what the peer reviewed science currently has to say about the plant.
Cannabinoids are a class of chemical compounds that act on cannabinoid receptors found mainly in the central nervous system and brain but also throughout different tissues in the body. Collectively this is referred to as the endocannabinoid system. There are endocannabinoids, which are produced within the body itself and there are phytocannabinoids found primarily in the cannabis plant. The number of cannabinoids identified in cannabis are in the ballpark of around 60-80 with the main constituents being Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). It’s interesting that these two compounds seem to have completely opposing effects; THC is the psychoactive component and may induce anxiety, while CBD has antipsychotic and antianxiety properties. Different strains of cannabis contain differing ratios of THC:CBD and this may account for the range of physical effects that are reported among the variety of strains available. There is mounting scientific evidence showing that phytocannabinoids may have medical value in the treatment of many neurological impairments, anti-inflammatory diseases, pain management, cancer treatment, and end of life palliative care. Due to irrational fears indoctrinated into society by the long standing illegal status of cannabis, an implicit goal is to isolate these benefits from the psychoactive component of cannabis, and while that may be possible and a worthwhile goal in some cases, it seems to be putting up unnecessary hurdles as the combination of phytocannabinoids, working together in the body, may be provide a synergistic effect and THC itself is not devoid of benefits. Unfortunately, even though scientists have known about the potential benefits of therapies targeting the endocannabinoid system since the 1970’s, research has been hindered due to the status of cannabis as a schedule 1 drug, so even if cannabis is fully legalized soon, we’ll be playing catch up with an area of science that is now over 40 years behind.
Neurological Disorders
The endocannabinoid system is now known to have an important role in maintaining synaptic plasticity in the brain. Synaptic plasticity is a general term in neuroscience that refers to the ability of the brain to change and adapt; effecting things like learning, memory, and other cognitive processes as well as sensory and motor functions. It’s thought that the endocannabinoid system has a role in immunity and offers protection against inflammation and neurodegenerative processes as well. Studies have shown an impaired endocannabinoid system existing in diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s, Parkinson’s and Alzheimer’s diseases. Many of those same studies have also experimentally determined that selectively activating the cannabinoid receptors in these disease states can help alleviate symptoms and slow down disease progression (refer to the previous link to find these studies for more in depth info).
Pain Relief
There are roughly 300 million people in the United States and 100 million who suffer from chronic pain. A concerning number, which, staggeringly accounts for as much as $635 billion dollars in pain management and loss of worker productivity in 2010. The endocannabinoid system also has a role in pain transmission, with cannabinoid receptors found throughout the peripheral and central nervous system. There are numerous animal studies that have been produced indicating that naturally occurring cannabinoids produced within the body can provide relief from pain and inflammation. Despite the promising pre-clinical research, there has only been one clinical trial conducted on human subjects who suffer from chronic pain due to osteoarthritis. The trial was designed around a compound that inhibited a specific enzyme that would lead to elevated levels of the endocannabinoid anandamide (AEA), a method proven to be effective in mouse models. However, the trial ended prematurely, concluding that the inhibitor was not effective at relieving pain. There is a dire need to find effective treatments for chronic pain, considering the debilitating societal and economic effects brought on by traditional opioid pain relievers. If nothing else, the failure of this one study underscores the need for more research to be conducted in this area. Most of what we know of cannabis’ role in pain relief is anecdotal and remains to be properly evaluated due to cannabis’ classification as a schedule 1 drug. We can look toward the current use of medicinal cannabis in palliative care of cancer patients as we will see later.
Cancer
Perhaps the first study to discover the anti-cancer properties of cannabinoids was published in 1975 in which certain isolated phytocannabinoids, were shown to inhibit tumor growth in mice and increase survival rates. Progress since then has been slow, again due to the schedule 1 status of cannabis, but there have been new insights within the last two decades into the mechanism that cannabinoids use to exert their effect. First, the cannabinoids that activate CB1 receptors such as THC have been found to generate a type of lipid called ceramide after CB receptor activation. Ceramide stimulates a pathway leading to the upregulation of a protein called ERK. ERK has a role in regulating cellular metabolism and cell growth. In cancer cells, sustained activation of this pathway by cannabinoids leads to apoptosis (cell death) while offering a protective advantage to normal, healthy, cells. Another important finding is that cannabinoids inhibit matrix metalloproteinases (MMP’s), which play a role in cancer metastases. The ability of cancer to spread to other places in the body makes it difficult to treat, so the discovery of compounds that can inhibit this process, as cannabinoids seem to do, is an important part of finding an effective treatment for cancer. There are other possible mechanisms at play, and they probably have a synergistic effect in killing cancer cells, but this mechanism seems to be receiving the most attention. Plant based cannabinoids, such as THC, as well as synthetic cannabinoids have been shown to induce cell death and inhibit tumor migration in various cancer cell lines in vitro: leukemia, prostate cancer, brain cancer, and cervical cancer, to name of a few studies. Additionally, the non-psychoactive cannabinoids such as CBD have been receiving an increasing amount of attention with a few dozen studies published (see Table 1 in this article) just in the last 10 years that perhaps show an equal effectiveness at combating multiple types of cancers in cancer cell lines, with a mechanism that may be more focused on anti-oxidant activity.
This does not mean cannabis can provide a cure for cancer. Many things can cure cancer in a glass dish, or even in mice, but that doesn’t always translate to a cure in humans. For example, how would we administer the cannabinoids while maintaining bioactivity? We don’t know if ingesting or smoking cannabis would allow for biologically active amounts of cannabinoids to target cancer cells. The limited number of available preclinical studies have suggested that cannabinoids would likely not work alone but would probably serve to enhance existing chemo and radiation therapies. Still, with cancer death rates in holocaust-level proportions, killing a little over half a million people every year in the US alone, we’ve allowed 40+ years of potential clinical research on cannabis to pass us by. To call that a shame would be a grossly inadequate and underwhelming statement.
Medical marijuana has still found a place in the realm of palliative care of cancer patients undergoing chemotherapy. Although there is limited actual clinical data, there are innumerable anecdotes of medical cannabis effectively reducing pain, nausea and vomiting that is brought on by traditional chemotherapy and radiation. Cachexia, a symptom of these therapies, is characterized by loss of appetite, weakness and extreme loss of body weight. Medical cannabis use has been reported to reduce cachexia by stimulating appetite and that alone is reason enough to advocate for its use because maintaining a healthy body weight is a very important component in the treatment of cancer. Also of note, treatment of HIV/AIDS symptoms with medical cannabis can be effective for the same reasons. There are synthetic alternatives to the cannabinoids derived from the cannabis plant: Marinol, Nabilone, and Sativex. However, these alternatives are not as effective as cannabis and can be prohibitively expensive.
To put the issue into perspective in regards to palliative care in cancer treatment: we still do not have the ability to specifically target cancer. As a result, we use harsh radiation and chemotherapy treatments that can not discriminate between healthy cells and cancer cells and instead has the potential to kill every cell, good or bad. It’s like carpet bombing an entire state to take out the capital without killing all of the citizens; in cancer treatment, you hope to do just enough damage to kill the cancer cells without killing the patient. So with such minimal and acute negative effects associated with cannabis, why are we even having this long drawn out conversation over whether or not to at least allow its use in this context?
Negative Side Effects
The debate over the legalization of marijuana has largely been hindered by the focus of the conversation on the potential negative health effects brought on by habitual use. There have been multiple attempts through the years to quantify the cumulative health effects. However, these have been so far limited to epidemiological studies, which can allow you to selectively pull data from a given population to draw conclusions to fit a certain narrative. Does cannabis use actually lead to an increased incidence of schizophrenia cases as some studies suggest? It’s probably just as likely that people with schizophrenia have a greater tendency to seek out mind altering substances, perhaps as a way of self medicating. The answer may be a little more nuanced and both of these scenarios could be false or partially true in certain at-risk individuals or those who smoke in adolescence. MRI studies have revealed that brain development occurs well into adulthood, and perhaps up to 30 years of age. Very young people may be particularly vulnerable to anything that acts on the brain. Studies have indicated that cannabis use before 17 years of age may result in poorer outcomes in regards to attention, memory, and impulsive behavior later in life, even with abstinence. There is little to no disagreement over the negative consequences stemming from adolescent substance abuse in general, developing brains simply should not be exposed to mind altering substance. However, the issue is still somewhat muddied when there may be certain predictors that predispose susceptible individuals to this type of behavior early in life.
By and large, there is no disagreement between studies suggesting that short-term memory is hampered by cannabis use, users may also be more likely to develop false memories. The long-term effects on memory are not as clear with some MRI studies showing that long-term memory is unaffected in heavy users. A major deficit to these studies is that they fail to control for participants who began using in adulthood rather than adolescence, making it impossible to tease out factors that may be influenced by the use of cannabis at a susceptible age of brain development.
Correlation is a problem we see again when trying to evaluate the cancer risk of an illegal substance like cannabis, because users may also smoke tobacco. Attempts have been made such as this review that examined the current scientific literature and found 16 studies that looked at cancer risk in groups of cannabis users. Some of those studies found an increase risk in head and neck cancers and lung cancer, others have found a decreased risk in other types of cancers. All the studies were flawed, however, as none of them controlled for tobacco use and there was no way to evaluate a dose response to cannabis use. I found one study that did control for tobacco use and found no correlation between cannabis smoking and lung cancer. Most studies seem to agree that although smoking cannabis does not lead to major changes in pulmonary function when compared to tobacco, they may still be at risk for developing bullous disease and spontaneous pneumothoraces. It may not be a good idea to smoke the plant, or any plant for that matter, our lungs may be resilient but they were designed to take in (mostly) clean air. Fortunately, there are alternative methods to smoking that are probably safer.
Current State of Legalization
Photo credit: Lulu Hoeller
Cannabis has been enjoyed for medicinal and recreational purposes for thousands of years. In 1937 the United States government passed the Marihuana Tax Act, prohibiting non-medical use of the plant. In fact, the term “marijuana” may have come into use as a means to add stigma by using a “foreign sounding” name to the plant that was traditionally called cannabis in America. By the 1950’s, Congress enacted the Boggs Act and the Narcotics Control Act which mandated sentences for drug users. The 1970’s made possession of cannabis completely illegal as it was classified as a schedule 1 drug by the Uniform Controlled Substance Act, which includes any drug with a high potential for abuse and no accepted medical value; a list that includes heroin, ecstasy, LSD, magic mushrooms and bath salts. Despite the schedule 1 status, no deaths have been directly attributed to cannabis, nor is there a known lethal dose, and we have already explored the medical value of the plant. Recreational use has been allowed on the state level in Colorado for over a year now. The result has been overall positive for the state as violent crime rates and traffic related fatalities have been on the decline, $8 million has been used to fund education and the state has enjoyed the lowest unemployment rate in recent history. On a related note, the country of Portugal has decriminalized drugs entirely for the last 14 years, with an overall positive trend toward decreased drug use and drug related deaths due to more resources being available for the treatment of addicts, as well as a decreased fear of punishment among addicts seeking treatment.
Unfortunately, money tends to dictate policy rather than science, rational discussion and public opinion. In the United States, alcohol is the third leading cause of death, as of the year 2000, and accounts for as much as 12% of the total health care costs in the country and an estimated total cost of $837 per person, per year. Collectively, beer, wine and liquor lobby groups spend a little over $6 million to influence members of Congress, which is a low amount considering the revenue brought in by these businesses (Congress can be bought off cheaply). So it may come as no surprise that they are among the top 5 contributors lobbying against relaxation of laws surrounding cannabis possession and use, other groups include police unions, private prisons, pharmaceutical companies and prison guard unions, all stand to lose money over federal legalization. Let’s not forget other groups such as Partnership for a Drug Free America and Community Anti-Drug Coalition of America, who petition against cannabis, yet are conveniently absent on issues like prescription drug abuse as the death toll from prescription pain killers rise to 15,000 deaths per year. Clearly, the real issue revolves around money.
Conclusion
I’ve tried to focus this article on the available scientific evidence and have not spoken of the ever growing mountain of anecdotal evidence of cannabis being used to treat epilepsy, PTSD, anxiety, ADHD, people throwing out their opioid pain killers in favor of weed; or even the benefits of hemp. Nonetheless, cannabis is far from a panacea nor is it the demon we’ve been lead to believe over the last century. There’s seems to be more potential good than harm when evaluating the issue as a whole and looking at the results in places that allow its use currently. That potential is something that we should always have been allowed to explore.
Critical Examiner 