The opioid crisis and the need for alternatives

Several major barriers have affected the research, availability, and approval of medical cannabis for facial pain. The United States currently faces two crises: the epidemic of opioid abuse and the epidemic of untreated and undertreated chronic pain. Over one third of the American population has some form of acute or chronic pain, and nearly 40% of older adults require treatment for chronic pain. Given the relative lack of effective non-opioid drug therapies for pain, there has been a dramatic increase in opioid prescribing in an effort to treat this enormous number of patients with pain. This effort has unfortunately led to our current epidemic of opioid dependency and abuse, with approximately 2.5 million Americans affected by opioid addiction in 2014. 

The current crisis that stems from the widespread availability of opioids clearly suggests the need to explore alternative pharmacological options for the millions of Americans afflicted with chronic pain. Humans have been cultivating cannabis, also known as marijuana, since as early as 12000 BCE, with the first writings documenting its medicinal applications originating from China in 2700 BCE. Various ancient Egyptian texts also describe its use for a variety of ailments including epilepsy and pain. 

Cannabis arrives in the west

It was largely unknown to Western civilization until 1839 when an Irish physician returned from India with a large quantity of cannabis for study regarding its clinical utility. Throughout the 19th and early 20th centuries marijuana was widely used for the treatment of headaches, tremors and epilepsy, but it slowly fell out of favor as pharmacology and drug development became more sophisticated and synthetic agents became available. 

A number of political and economic forces led to our current bans on cannabis use including maneuvering by the nylon industry to eliminate competition from marijuana-derived hemp. Despite protests by the American Medical Association and other physician groups, cannabis was declared a Schedule 1 (high abuse potential with no medical use) drug in 1970, though efforts continue for its classification as a Schedule 2 (high abuse potential with potential medical use) drug. The classification of cannabis as Schedule 1 has limited its availability for study in clinical trials and for use in treating medical conditions. 

What is cannabis?

Medical cannabis represents a collection of natural and synthetic drugs. The most common form for medical use is the cannabis plant, Cannabis sativa. The cannabis plant contains over 60 active chemicals. Also known as cannabinoids, these chemicals alter the levels of various signaling molecules on neurons in the brain. Two of the most important cannabinoids in naturally-occurring plants are tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is psychoactive, and provides the well-known “high” associated with marijuana. It has also been shown to have anti-seizure, anti-nausea, and appetite stimulation effects. CBD is not psychoactive, but does demonstrate pain relieving effects. In fact, the World Health Organization (WHO) declared in December 2017 that CBD has little potential for abuse but has promising potential for medicinal use. 

In recent years, the levels of THC in illicit cannabis plants seized by the FDA have been steadily increasing. This increase has resulted from selective breeding of the plants to increase THC concentrations to provide the user with a more intense high. The plants may be dried and smoked or ingested as an ingredient within any of a number of different foods or drinks. Vaporizers are also an efficient method of inhaling the drug, and there are a number of commercially-available methods for doing that. 

Synthetic cannabinoids

Synthetic cannabinoids are medications produced by drug companies, each with its own tailor-made concentration of chemicals. For example, dronabinol and nabilone are FDA-approved formulations with relatively high THC / CBD ratios, and thus are effective for the treatment of nausea, vomiting, and wasting associated with chemotherapy. Meanwhile, there are a number of synthetic cannabinoids in development with lower THC / CBD ratios to enhance their effectiveness as pain relieving medications while limiting their psychological side effects. 

Cannabis approved for medical use

In 1996, California legalized the medical use of cannabis for select medical conditions, despite its classification as an illicit drug at a federal level. Patients required certification by a physician that they had one of these medical conditions, and once certified, could receive medical cannabis from any of a number of statewide dispensaries. This model was adopted by several more states over the subsequent two decades. As of early 2021, 36 states, Guam, Puerto Rico, the US Virgin Islands, and the District of Columbia have legalized medical cannabis in some form increasing its availability to those in need and enabling more robust study of its efficacy. 

Given its illegal status on a national level, it is illegal to distribute cannabis across state lines, and the money associated with this distribution is not allowed to move within the interstate banking system. These limitations have blunted the expansion of the medical cannabis industry, and limited the interest in the industry by the major pharmaceutical companies. 

Consequently, there have only been a handful of clinical trials of medical cannabis for the treatment of pain to date. Taken together, the data  so far suggests that inhaled cannabis was slightly more effective than gabapentin, a medication in widespread use for the treatment of chronic neuropathic pain. Of six randomized, controlled clinical trials using the synthetic cannabinoids, five compared one of these drugs to a placebo and found significant gains in pain relief, although sample sizes in each study were fairly small. 

Side effects of cannabis for facial pain

As with every pain medication, medical cannabis is associated with some adverse effects, including motor, short term memory, and judgment impairment, as well as paranoia at higher doses. One study looked at the safety of cannabis use for pain over a one-year study period in about 430 patients and found no difference in severe adverse events over the life of the study. Additionally, while there is some concern for addiction with cannabis use, its propensity for addiction is far lower than opioids, alcohol or tobacco. 

To date there have been no documented deaths due to overdose from cannabis use. While it is both illegal and ill advised to drive under the influence of cannabis, studies have found that traffic fatalities have actually decreased in states where medical cannabis was legalized compared to states in which it remains illegal. The exact reason underlying this decrease is unclear but it may be due to decreased use of other psychoactive drugs in the setting of medical cannabis use. 

The notion that cannabis is a gateway drug has also been widely disseminated and it is true that medical marijuana laws do increase cannabis use among adults. However, if the theory that cannabis is a gateway drug is true, it would be reasonable to think that opioid abuse and overdose related deaths would increase in states in the years following legalization of medical cannabis. It has actually been found that states with medical cannabis laws demonstrated lower rates of opioid overdose compared with states without these laws and the longer the laws were in place the more robust the effect became. Thus, the data suggest that the adoption of medical cannabis laws appears to have a protective effect in the prevention of opioid overdose deaths, possibly because individuals use cannabis, which does not cause death even at high doses, rather than opioids, which is lethal at high doses. 

Given the enormous population of chronic pain patients and limited available drug treatment options, the United States must develop novel, non-opioid drug treatments for pain. It is important to have new drug treatments so that pain can be effectively treated while reducing the potential for opioid abuse. Medical cannabis represents one of these safe and effective non-opioid treatments. Moving forward, it will be important to reclassify cannabis as a Schedule 2 drug to allow for more research and development of this class of medications. The legalization of medical cannabis will then allow the cannabis industry to more fully develop, and once large pharmaceutical companies become invested in its development, the full potential for this medical therapy can be discovered. While medical cannabis may not be the right answer for all patients there is enough existing evidence that its use for pain relief should not remain stigmatized and shunned. Only by providing other viable alternatives that actually treat our patients pain can we begin to tackle the epidemic of opioid prescribing and abuse and better care for the millions of Americans afflicted with chronic pain.