Approximately 50 million Americans, or around 20%, have some form of chronic pain¹. The cost of treating pain in the US is staggering: annually, it has been shown to cost up to $635 billion². These costs increase as pain severity worsens, which it often does for many people. Even more concerning is how pain affects quality of life. Chronic pain has widespread biopsychosocial effects, negatively impacting mental health, sleep, family, work and social functioning³. Pain is one of the most concerning health issues of the 21st century.

Not surprisingly, treating pain is a massive industry. A wide range of over the counter and prescription drugs are consumed by millions on a daily basis. At best, these products provide short-term relief; at worst, they contribute to an ongoing opioid epidemic that has claimed over half a million lives⁴. Most medications, including over the counter ones, carry a risk of side effects. Even non-steroidal anti-inflammatories like aspirin kill over 7,000 people a year⁵. Clearly, safe and effective treatments are desperately needed.

Pain and Cannabis

Cannabis has emerged as a popular treatment for pain in recent years, and the majority of medical cannabis users are seeking pain relief. In fact, a recent study that looked at almost 650,000 medical cannabis users found that 62% are using it to treat enduring pain⁶. Many of these users report benefits, with a 2018 survey finding an average of 74.7% pain reduction in response to the question “How effective is medical cannabis in treating your symptoms or conditions?” ⁷

While medical cannabis can refer to smoked or vaporized whole plant cannabis, an increasing number of alternative forms of “cannabis-based medicines” are now available. These include oils, capsules, oral sprays, and edibles, to name a few. The main players in these preparations are tetrahydrocannabinol (THC) and cannabidiol (CBD), which are the major cannabinoids. THC and CBD have been used in isolation, as well as in combination, in the treatment of pain. Some products will also contain minor cannabinoids as well as other molecules like terpenes and flavonoids. In addition, there are several cannabis-based pharmaceutical medications, including Marinol, Syndros, and Cesamet (which are synthetic THC compounds), and Epidiolex and Sativex (which are naturally derived CBD and THC/CBD compounds, respectively).

Research Evidence

When evaluating clinical research, the highest quality evidence comes from meta-analyses, which are statistical analyses that combine results from multiple studies. In this way, they provide a truer effect that is less distorted by the errors that are likely found in individual studies. There have been several meta-analyses published looking at the effect of cannabis-based medicines containing THC over the last several years. The most recent, published by Yanes and colleagues in 2019⁸, analyzed 25 studies with a total of 2,248 patients. Treatments included plant cannabis (as the whole plant or a plant extract) and synthetic cannabinoids, and subjects had pain from a variety of conditions, including cancer, fibromyalgia, arthritis, neuropathic pain, chronic pain, headache, and diabetes. The analysis found that pain decreased substantially with cannabis treatment. Similar findings were also observed by two other recent meta-analyses^9,10.

This convincing body of clinical research has led to cannabis being recognized as an effective treatment for some pain conditions in both the US and Canada. In 2017, the US National Academies of Sciences, Engineering and Medicine published a statement that the use of cannabis for the treatment of pain is supported by well-controlled clinical trials and that there is substantial evidence that cannabis is an effective treatment for chronic pain in adults. The report also concluded that “cannabinoids likely have a natural role in pain modulation.” ¹¹ Similarly, in 2014, the Canadian Pain Society revised their consensus statement to recommend cannabinoids as a third-level therapy for chronic neuropathic pain¹². The use of the term “cannabinoids” by these groups is a bit confusing, as there are over 120 cannabinoids that have been identified in the cannabis plant. It’s worth mentioning that these recommendations were based on studies using whole plant cannabis (which contains a wide range of cannabinoids, terpenes, flavonoids, and other molecules), various preparations of THC, and THC in combination with CBD. None of the studies used CBD on its own.

The vast majority of research on CBD and pain in humans has used CBD in combination with THC, usually as the pharmaceutical medication Sativex. Sativex is an oromucosal spray made from cannabis plants that delivers a standardized dose of 2.7mg THC and 2.5mg CBD (an almost a 1:1 THC:CBD ratio), along with other cannabinoids, flavonoids and terpenes in unmeasured amounts. Looking specifically at studies using Sativex, a recent comprehensive review found that it was an effective treatment for pain¹³. And, unlike for some pain medications, effective doses are stable over time. One study found that patients using Sativex to treat chronic non-cancer pain for a year experienced initial pain relief at a dose of approximately 7-10 sprays per day (about 19-27mg THC and 17-25mg CBD), without dose escalation or toxicity for 52 weeksM¹⁴.

Research has increasingly been studying CBD in isolation, especially given the passing of the 2018 Farm Bill that legalized hemp and hemp derived cannabinoid containing products in the US. However, clinical research on CBD is lacking for most medical outcomes, including pain. Pre-clinical research, though, has shown very promising results. In animal models of pain conditions that widely affect humans, including arthritis^15,16 and myofascial pain¹⁷, CBD has been shown to be a safe and effective treatment. At this point, there is an “overwhelming” body of preclinical research supporting the use of CBD for pain¹⁸.

Recently, a group of expert clinicians convened to evaluate the safety and effectiveness of a variety of medications used to treat pain, including cannabinoids. This evaluation was specific to chronic neuropathic pain, a type of long-lasting pain that is caused by progressive nerve disease, injury, or infection. Cannabis-based products consisting of THC and CBD in a 1:1 ratio were rated highest at 79 (out of 100), followed by CBD dominant products at 75, and THC dominant products at 72. In comparison, oxycodone scored in the 40s, and morphine and fentanyl in the 30s. The analysis found that even if the pain reduction and quality-of-life scores for THC/CBD and THC were halved, their balance of efficacy relative to safety would remain better than those of more commonly used non-cannabinoid drugs¹⁹. While these findings may not generalize to all types of pain, they highlight the impressive safety and efficacy profile of cannabinoids.

Although THC and CBD are the molecules from cannabis most widely used in the treatment of pain, other compounds in cannabis may also be helpful²⁰. Like THC and CBD, many cannabis-derived terpenes and flavonoids and several minor cannabinoids, including cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), tetrahydrocannabinolic acid (THCa), cannabidiolic acid (CBDa), cannabidivarin (CBDV), and tetrahydrocannabivarin (THCV) have been shown to reduce pain and/or inflammation, which is a primary cause of pain. At this point, most of the research on these molecules is limited to pre-clinical models, and the effects of minor cannabinoids, terpenes, and flavonoids in humans are not well understood. These may have pain reducing effects on their own, as well as in different combinations (termed the “entourage effect”).

Other Evidence

Cannabis has a very long history of being used to treat pain²¹. There is evidence of its use as a medicine in civilizations around the world going back thousands of years, including in Ancient Egypt, Greece, and India. Records show that cannabis was used to treat  a broad range of conditions like sore nails, pain with childbirth, and headaches. As recently as the early 20th century, it was widely sold in US pharmacies, and was one of the most popular medicines prescribed for pain. While this type of evidence does not satisfy modern criteria for evidence of safety and efficacy, the persistence of cannabis as medicine across millennia supports its therapeutic value, and can be used to provide some context for our current understanding.

Personalized Approach

Many health care providers using cannabis-based medicine recognize that a personalized approach is needed. Dr. David Bearman, co-founder of the American Academy of Cannabinoid Medicine and a board member of Americans for Safe Access, states that every person is different, and that many adjustments will likely be needed to find the optimal dose for each individual²². It’s important to note that this approach is not consistent with the scientific method. In clinical studies (with a few exceptions), all subjects are given the same dose of a medication in order to determine the effectiveness of the dose in that population. Because of this, there may be a disconnect between what people experience in real life and the research evidence, at least as far as optimal doses and effectiveness of cannabis-based medications. This concept of “personalized medicine” is being increasingly used with cannabis, and includes tailoring medical decisions, prescriptions, practices, and interventions to a specific individual.

Summary

Cannabis has long been used to treat pain, and there is increasing research supporting its use in a range of pain-related disorders. The medical consensus is that cannabis may be an effective pain reliever, which is illustrated by the position statements of the US National Academies of Sciences, Engineering and Medicine, and the Canadian Pain Society that support the use of cannabis and cannabinoids for the treatment of some types of pain. There is much less research specific to CBD or other non-THC components of cannabis and pain, although supportive pre-clinical evidence is accumulating, especially for CBD. Using a personalized approach, many people may experience pain relief from using cannabis, including the whole plant and other cannabinoid preparations.

References

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