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12 cannabis patient care | vol. 3 no. 1 cannapatientcare.com research focus Overview of Research on Cannabis for Chronic Pain B Y R U T H F I S H E R Types of Pain I N HIS 1999 ADDRESS to The American Society of An- esthesiologists, Michael Cousins stated that "chron- ic pain will be regarded as the disease of the 21st cen- tury" (1). Indeed, it is: pain is "a significant public health problem," afflicting some 11% to 40% of the US population (2). While people talk about pain as if it's a relatively homogene- ous problem, in reality, it's fantastically diverse, both in what causes it and in how people experience it. There are many different classification schemes for pain. One way to classify pain is by duration, either acute or chron- ic. Acute pain generally comes on suddenly, has a specif- ic cause–often tissue damage–and lasts for a limited period, until the wound has healed. In contrast, chronic pain lasts for a much longer period–more than six months in duration–and may be due to any variety of underlying causes (3-5). Notably, chronic pain "is totally different from acute pain because of its pathologic psychobehavioral manifestations" (6), such as social isolation and avoidance. Cancer pain is often multidimensional and may be either acute (for example, associated with tests or treatments un- dertaken to address the cancer) or chronic (such as associ- ated with the cancer itself) in nature. Likewise, fibromyalgia and other pain syndromes may be either acute or chronic in nature. And as with cancer, pain syndromes tend to be quite multidimensional and not well-understood (3-5). Another way to classify pain is by source, either nociceptive or neuropathic. Nociceptive pain is caused by a specific sen- sory stimulus: extreme heat or cold (burns or frostbite), toxic chemicals, or tissue damage, while neuropathic pain is caused by damage to or disease of the nervous system (3–5). Based on these two sets of classifications (duration and cause), there are four overlapping categories of pain: acute nociceptive, chronic nociceptive, acute neuropathic, and chronic neuropathic (see Figure 1). Cannabis and Pain Cannabis has been used throughout history to treat pain (7), and studies of people who use medical cannabis consistently report pain as being the most common target of cannabis relief (8–10). Scientific research on cannabis for pain was ignited when cannabis was reintroduced into society in the early 1990s with the discovery of the endocannabinoid system (ECS), and the research subsequently caught fire over the past 30 years (see Figure 2). While cannabis has shown little ability to address acute pain (11), there is a vast pre-clinical body of research examin- ing the mechanisms of action (MoA) of cannabis for address- ing different types of chronic pain. Additionally, there is also a substantial collection of clinical trials conducted to test the efficacy of cannabis for different types of chronic pain. Mechanisms of Action Direct MoAs of cannabis for reducing chronic pain include reducing chronic inflammation, acting on pathways of chronic pain signaling, and acting on acute and chronic cognitive per- ceptions of pain. Other indirect MoAs for cannabis to address chronic pain include improving sleep and enhancing the effect of other treatments for addressing pain. Reduce Inflammation Cannabis can reduce chronic pain by decreasing inflammation that causes pain. Typically, our immune system is triggered whenever our body senses trauma or toxins. Both tissue damage (nocicep- tive) and nerve damage (neuropathic) induce the same type of inflammatory response: nearby blood vessels dilate—causing heat and swelling—and become permeable, enabling various types of immune system cells to flood the site and manage the threat. Some of the substances released in the pro- cess "irritate nerves and cause pain signals to be sent to the brain." By inducing pain, your body is telling you to protect the affected region (12). Of course, acute inflammation is generally a productive re- sponse by your body to very real threats. However, for many people, inflammation transitions from being a productive, acute response to a short-term problem into becoming an on- going, noxious problem. In these cases of chronic inflamma- tion in which the process is no longer serving a useful re- sponse, cannabis can be used to inhibit the inflammatory process. More specifically, the immune system cells respon- sible for triggering cascades of activity that target perceived threats contain cannabinoid receptors (CBs), which mediate those cascades. As a result, cannabis can be used to act on