Pain management is one of our most revisited topics here on the Cornerstone blog. Our commitment to reporting studies related to pain management should come as no surprise to readers; pain relief accounts for a substantial portion of all medical cannabis use. Usually we update you on new findings within the field; however, today we are going to take a step back for a more general review, courtesy of Ethan Russo and Andrea Hohmann.

Medicine, as Russo points out, really began with plants. Our early ancestors would have noticed the effects of consuming plants within their environments and then learned to use those effects. Though we like to think of mankind as superior creators when compared to plants, humans are comparatively inefficient at producing pharmaceuticals. Plants have the surprising ability to produce complex chemicals like THC from sun, water, and dirt, whereas we have to build labs with precision machinery, electrical power, and contamination control! As a result, the first functional medicines were not human synthesized and instead came from plants. From coca leaves to morphine, these chemicals wove themselves into the history of human civilization. However, in modern times, plant-based chemicals are not generally accepted as medicine. This isn’t necessarily due to a bias against plants, but more importantly because plant-produced compounds are naturally inconsistent. In the case of cannabis, the way the plant is grown can greatly affect the profile of chemicals produced, not to mention the potency. Different buds on the same plant might even have significantly different ratios of chemicals. One of the strengths of Western medicine is the demand for rigorous testing and quantification. However, plants such as cannabis contain many chemicals in inconsistent ratios, which makes this kind of quantification difficult. This same strength has also barred society from using plant-based medicines that were already available to people hundreds of years ago. It’s a very silly situation to be in but without an easy solution. The good news is that the FDA does allow for plant-based medicines, and as Russo’s own Sativex is proving, cannabis in particular is likely to gain traction in the pharmaceutical industry.

Of the two cannabinoid receptors found in the brain (and Russo points out that there may be other types yet to be discovered), CB2 is responsible for much of the pain-relief experienced by cannabis users. Although scientists initially thought of these receptors as mere immune system regulators, evidence has been established for important CB2 pain relief functions in areas ranging from the brain and spine to the gut and limbs. For instance, cannabinoids can help signal food to move further along in the intestine or help dull the pain from skin irritation, all through CB2 receptors. Russo drives this point home to remind readers that the endocannabinoid system is responsible for pain management all over the body. The mechanism of pain management occurs in a variety of ways, however. In some cases, the decrease in pain actually comes from the anti-inflammatory properties of cannabinoids such as CBD (cannabidiol), rather than direct activation of the CB2 receptor. Many chronic pain conditions, such as arthritis, are actually the result of unnecessary inflammation, so anti-inflammatory agents may decrease pain. In addition, cannabinoids may also interact with other neurotransmitters involved with pain management to indirectly affect their actions. As Russo notes “cannabinoids specifically inhibit glutamate release” in some parts of the brain. Since glutamatergic mechanisms become hypersensitive during chronic pain, this is speculated to play a role in reducing pain. Finally, CBD, unlike THC, is also capable of activating vanilloid receptors. While little is known about the way these receptors work, this represents a fourth possible pathway through which pain management occurs.

Unfortunately, synthetic cannabinoids have not had much success on the market. Marinol, one of the first to be approved, is difficult to dose since it must be digested. While Marinol is successful as a hunger stimulant, pain management achieved is minor. In general, Marinol is not thought of as an effective pain medication. Russo goes on to make a long list of cannabinoid pharmaceuticals that have been released since Marinol, almost all with lackluster reviews until Sativex, his own product. As always, readers should be wary of the conflicts of interest of researchers (which is not to say the data is inaccurate). However, a concept that agrees with this data is that Sativex is one of the first to also contain CBD. As noted earlier, CBD seems to have more therapeutic pain potential than THC and particularly in combination with THC. This could be a large reason that many of those suffering from chronic pain still prefer to smoke or vaporize cannabis rather than using a synthetic THC like Marinol. Regardless, vaporization of cannabis containing high CBD has also shown to significantly decrease reported pain as discussed in previous articles.

What we’re ready for now are large, clinical trials of pain management through CBD and THC preparations. The largest study of Sativex only included 360 individuals. That may sound like a large number, and certainly represents a lot of work for researchers, but in terms of establishing the efficacy of a medicine, this is nothing. The most interesting evidence will arrive when Sativex is released beyond the medical cannabis market in the U.S. and thousands of patients can be observed. Before this happens, GW pharmaceuticals will have to finish preliminary testing to comply with FDA requirements. Although these requirements can seem frustrating while waiting for new medical options, they protect consumers from unnecessary exposure to risk with new medications, and cannabis, as safe as it is, cannot receive special treatment.



Works Cited

Ethan Russo and Andrea Hohmann. “Role of Cannabinoids in Pain Management.” (2013) Comprehensive Treatment of Chronic Pain by Medical, Interventional, and Integrative Approaches. American Academy of Pain Medicine.