Introduction : Promising Compounds, Changing Landscape

Cannabis has been used around the world for centuries and the purpose for its use has varied throughout that time.¹ However, the utilization of cannabis for medicinal purposes has been consistent. Starting with the Chinese around 2900 B.C., many civilizations have transcribed their use of cannabis for a variety of conditions, from joint pain and muscle spasms to conditions such as gout and malaria.¹ While cannabis has been deployed medicinally for myriad medical conditions, the scientific rationale for its efficacy for these conditions is, in many cases, not clear. Four thousand years later, scientists are still trying to determine the exact medical conditions, if any, cannabis is effective in treating.

Research into cannabis and its uses has been hindered by a debate over its legality.² In 1976, the United States Controlled Substances Act classified cannabis as a Schedule I drug, meaning that it has a high potential for abuse and no accepted medical uses. However, as of March 2017, 28 states and the District of Columbia have enacted laws allowing the medical use of cannabis and 8 states, plus the District of Columbia, have legalized recreational use of cannabis.³ The accepted conditions vary from state to state, in large part, due to the lack of randomized placebo-controlled studies researching the efficacy of cannabis for specific ailments.⁴ Despite a paucity of standardized and controlled trial research to evaluate the short- and long-term health outcomes of cannabis use, all states are consistent in including chronic pain as one of the conditions for which cannabis is an approved pharmacotherapy. Indeed, pain relief is the most commonly cited reason for the medical use of cannabis.^4–6

Whether cannabis is the best treatment for pain or not, many patients around the world believe that cannabis has helped them with their pain.⁷ As more and more states legalize cannabis for medicinal uses, a greater number of patients will ask their healthcare provider if it would be an effective treatment for their condition. Healthcare providers are in a difficult situation: there are only two cannabinoids currently approved by the United States Food and Drug Administration, and state regulations require them to recommend cannabis broadly, leaving the details about cannabis strains and dosing to be determined at the dispensaries. Interest in the use of cannabis for pain may be further catalyzed by a recent report put forth by the National Academies Committee on the Health Effects of Marijuana,⁸ in which the authors concluded that there is “conclusive or substantial evidence” that cannabis is effective for the treatment of chronic pain in adults. Furthermore, even if physicians do not recommend cannabis for their own patients, they should at least be educated regarding the extensive effects of cannabis. Unfortunately, many patients currently use cannabis to treat a host of medical problems and do so without contacting their healthcare provider.⁷ Healthcare professionals need to be prepared to answer questions regarding cannabis use and the potential effect it would have on each patient’s treatment.

Cannabis and pain: a brief history

The utilization of cannabis for pain can be traced back to ancient Chinese texts, dating to 2900 B.C. The Shennong Ben Cao Jing, a Chinese encyclopedia on agriculture and medicine, contains the oldest written record of cannabis as a medicine, recommending cannabis for constipation, rheumatic pain, female reproductive tract disorders, and malaria.⁹ Furthermore, the plant was used in conjunction with wine to anesthetize patients during surgical procedures.¹⁰ The Chinese mostly utilized cannabis seeds that contain very low levels of delta-9-tetrahydrocannabinol (Δ⁹THC), one of the main compounds in cannabis thought to have therapeutic effects.¹⁰

Around 1000 year B.C., more parts of the cannabis plant started to be used medicinally in India. The female plant’s flowers were utilized and three different preparations of cannabis with varying degrees of potency were developed.⁹ The strongest preparations were used as an analgesic, hypnotic, tranquilizer, antispasmodic, and anti-inflammatory agent.^11,12 It was not until the early 19th century that cannabis started to be explored in Western medicine.¹³

Although the use of cannabis as a medicine in western cultures started off slowly, by the end of the 19th century, over 100 publications on medicinal cannabis were published in Europe and the United States.¹⁴ Within that time, the medical indications for cannabis mostly focused on its hypnotic and analgesic effects. Since then, medical cannabis use has waxed and waned due to legal restrictions as well as the difficulty with replicating its effects between individuals.^11,15 Since the 1960s, both recreational cannabis use and medicinal cannabis use have increased rapidly in the United States. In 2015, an estimated 22.2 million Americans aged 12 or older were current users of cannabis, which corresponds to 8.3% of the U.S. population aged 12 or older.¹⁶ Recently, research into cannabis expanded exponentially and the use of cannabis for pain became one of the most widely studied subtopics.¹⁷

There are two ways to consider the rationale for cannabis pharmacotherapy for pain, conceptually and according to the evidence base. In this review, we will examine both.

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