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Cannabis for Pain, a Review of What We Know

The statistics on chronic pain make it clear just how prevalent a problem it is in the US. Anywhere from 11 to 40 percent of American adults experience chronic pain, “with considerable population subgroup variation,” according to the Centers for Disease Control and Prevention (CDC).

Chronic pain is a top reason Americans head to the physician’s office. It’s a medical condition commonly associated with decreased quality of life, dependence on opioids, correlated mental health issues, and decreased mobility and function. 

Chronic pain is a primary reason why patients turn to medical cannabis. Patients consistently report pain and related painful medical conditions as the number one reason for medical cannabis use. According to RYAH Data’s own numbers, it’s the fourth most common condition behind anxiety, depression, and stress.

Because September is Pain Awareness Month, it’s worth reviewing what we know about the therapeutic value of cannabis for pain. Despite how many patients now rely on the plant to soothe chronic pain, the science isn’t clear cut. The specifics continue to elude researchers, including which cannabinoids (or combinations of cannabinoids), which strains, and what doses are most effective.

Conclusions from the National Academies of Sciences, Engineering, and Medicine 

In one of the most robust reviews on cannabis as medicine to date, the National Academies of Sciences, Engineering, and Medicine published a report entitled, “The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research.” In this expansive 2017 literature review, the Academy made several substantial conclusions about cannabis. One of the most decisive was the conclusion that “there is substantial evidence that cannabis is an effective treatment for chronic pain in adults.”

Of the five systematic reviews included in their analysis of cannabis for pain, “conclusions across all of the reviews were largely consistent in suggesting that cannabinoids demonstrate a modest effect on pain.” The research included within these studies covered mostly plant-derived cannabinoids, and mostly for neuropathic pain (although other types of pain including cancer/chemotherapy-related pain, rheumatoid arthritis, multiple sclerosis, and musculoskeletal issues were also explored).

The majority of the studies used either a pharmaceutical preparation of cannabis (nabiximols) or flower (smoked or vaporized) in these early-stage trials. The Academy report determined that across all included research, “plant-derived cannabinoids increase the odds for improvement of pain by approximately 40 percent versus the control condition.”

Notably, this report did not provide an analysis of effective dosage, strain, or cannabinoid concentrations in the treatment of pain. It also pointed out that most of the research explored relied on pharmaceutical preparations or product provided by the National Institute on Drug Abuse. Neither of these options accurately represents the products available to patients today, as we have discussed in previous posts on the problems with cannabis research.

No Consensus on Specific Cannabinoids for Pain

There is a battle playing out between the pro-THC and pro-CBD sectors, as they vie for policy change and a patient’s purchasing power. Does either of these primary cannabinoids work better for treating pain than the other? Much of the available research contradicts itself, with headlines like “Study shows cannabis flower with high THC levels is effective for pain relief” and “Cannabis pain relief without the ‘high’ :Mechanism of cannabidiol for safe pain relief without side effects.” There is seemingly no consistent trajectory in study findings.

RYAH Data’s September Report on Pain told us that patients overwhelmingly prefer THC-rich strains of cannabis for use with chronic pain. Anecdotal information tells us the top strains for pain used within the Ryah Data ecosystem were typically over 15 percent THC, with little to no measurable CBD content. At the very least, this data set suggests that patients prefer potent THC-rich strains over less-intoxicating varieties. However, other studies (such as the one mentioned earlier) show how CBD can help reduce the experience of pain, “without the high.”

In terms of dose, both CBD and THC have a measurable dose-dependent inverted U-shaped curve for efficacy. Mild doses of either compound do not produce effective relief, while high doses tend to create an adverse reaction. In the case of THC, large doses may even trigger an increase of pain during a brief, albeit highly uncomfortable, acute marijuana intoxication.

What about in combination? Because of the known antipsychotic effects of CBD, especially paired with THC, these two compounds may very well work in a synergistic relationship for the treatment of pain. There is already a pharmaceutical preparation of cannabis, containing a 1:1 ratio of THC and CBD. Nabiximols (trade name, Sativex) is approved in Canada and many European countries for the treatment of neuropathic and spastic pain related to multiple sclerosis. It is also under investigation for diabetic pain.

Effective for Pain, But with Few Details

Patient use of cannabis for pain still dramatically outpaces research on the subject. Experts and research teams continue to struggle to determine dosage guidelines, strain suggestions, and even the perfect cannabinoid ratio. Despite the lack of specifics, it hasn’t dampened interest in the plant for use with chronic pain. According to a recent survey by the American Society of Anesthesiologists, “More than two-thirds of those surveyed said they have used or would consider using marijuana or cannabinoid compounds – including cannabidiol (CBD) and tetrahydrocannabinol (THC) – to manage pain.” 

One of the explanations for the gap between the anecdotal evidence and clinical results is the pharmacological tendency of molecular isolation. Traditionally, pharmaceutical research explores one single compound in isolation. Cannabis, like many other botanicals, defies this methodology. Cannabis contains hundreds of chemical compounds, all of which may work together for therapeutic benefit under the theory of the Entourage Effect. 

One example of the Entourage Effect is the ability of CBD to mitigate the intoxication of THC. As another example, many non-psychoactive compounds in the plant may also improve analgesic benefits. Recently, researchers discovered two cannabis-specific flavonoids called cannflavin A and B. In their early in-vitro work, the team explored possible methods of biosynthesis of these compounds, which “exhibit anti-inflammatory activity that is thirty times that of aspirin.” 

While the world focuses on cannabinoids for pain (THC, CBD), we largely ignore how these minor compounds may impact the therapeutic value. As the Entourage Effect postulates, cannabis may be valuable as a whole, not just for the sum of the individual parts.

At a distance, there is a medical consensus that cannabis is an effective option for chronic pain treatment. However, as soon as we drill down to the details, the details evade detailed medical summary. Consistently, patients around the world report use of cannabis for the effective relief of chronic pain, but well-controlled studies are lacking or fail to replicate these results to the extent of the anecdotal evidence.

Going forward, the research will need to adapt to better reflect the actual cannabis products used by patients in their homes. We can eliminate many of the current issues within the research by adopting dose-measured inhaler technologies and traceable and tested prefilled cartridges. The technology is here to give researchers the capacity to investigate, in a controlled manner, the real-world use of cannabis by chronic pain patients. 

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