Cannabis and pain – A research perspective
Background
The controversial plant Cannabis Sativa L, or Cannabis, (i.e., marijuana and hemp) has been utilized for thousands of years for wide range of purposes, including as a medicine.1 One of its earliest medical uses was as an analgesic (i.e., pain-reducer). Historical documents indicate that Cannabis was used as a surgical anesthetic in ancient China nearly 2000 years ago.2 Anesthesia is the ultimate form of pain control. Its use as a treatment for pain has also been documented in ancient Israel, Greece, Rome, and India.3
Cannabis has also been used to treat pain in the United States. It was added to the United States Pharmacopeia (USP) in 1851 (The USP is a compendium of drug information. It also sets standards for dietary supplements and food ingredients that have a role in US federal law).4 The leading pharmaceutical companies of the day developed and manufactured Cannabis-derived drugs, mostly liquid extracts (i.e., tinctures), including Eli Lily, Wyeth, Park Davis (See Figure 1).
Figure 1
Use faded in the late 1800s as morphine and aspirin were developed and Cannabis fell out of favor, mostly due to exaggerated, and some outright false, claims about its deleterious effects on individuals and society.5 Cannabis would soon become prohibited with the passage of the Marijuana Tax Act in 1937. Five years later, it would be removed from the USP. It remains absent to this day.
Pain is a big problem
Chronic pain is a big problem in this country, and around the world. It is one of the most common reasons adults seek medical care. Pain can result in restrictions in mobility and daily activities, as well as induce other medical conditions, like anxiety, depression and sleep disorders. Further, pain-related medical services and loss of productivity costs the United States economy close to one trillion dollars annually.6
Currently available analgesic medications are limited by low efficacy, high adverse effect rates, cost and other factors. New approaches are needed. In 2016, more Americans died from an overdose of an opioid – prescription and non-prescription – than from motor vehicle accidents or from gun violence (Approximately 42,000).7 The number of Americans that died from an overdose of Cannabis in that same year was…zero.8
A brief review of selected studies
In the past several years, there has been an explosion of anecdotal evidence reported by patients, and healthcare providers, claiming Cannabis is a safe and effective treatment for multiple types of pain (e.g., inflammatory, neuropathic, etc.). Some of these patient and provider reported outcomes have been systematically collected, analyzed and published as empirical, observational studies.
For example, a cross-sectional study published by Michelle Sexton, ND and Laurie Mischley, ND, PhD , MPH in 2016 found that pain was the most common medical condition for which survey respondents used Cannabis (See Table 1).9 There are other studies that corroborate their findings.10
Table 1 - Total Number and Percentages of Medical Cannabis Users Reporting Use for Each Medical Condition
Similar studies have been undertaken to investigate the medical use of cannabidiol, or CBD, the non-intoxicating, hype-inspiring phyto-cannabinoid widely considered to be the decaffeinated cousin to delta-9-tetrahydrocannabinol, or THC. I co-authored a cross-sectional study of cannabidiol users in 2017. Among other things, Joy Phillips, PhD, my co-author and I, found that “Chronic Pain” and “Joint Pain” were the most commonly reported medical reasons for using CBD (See Figure 2).11
Table 2 - Number of medical conditions for which respondents reported using CBD, by medical condition (n = 3963). CBD, cannabidiol; COPD, chronic obstructive pulmonary disease; PTSD, post-traumatic stress disorder.
Michelle, Laurie and I teamed up to publish another cross-sectional study in 2017.12 We investigated prescription drug use among medical Cannabis users. We found that almost two-thirds of medical Cannabis users reported substituting Cannabis for a prescription drug. The most common class of drugs substituted was “Narcotics/Opiates”. “NSAIDs/non-opioid analgesics” were the 4th most common class of drugs substituted, behind anxiolytics (i.e., anxiety lowering) and anti-depressants (See Figure 3).12
Figure 3 - Number of reported prescription drug substitutions, by drug category, during 2016 (n=2,473). Abbreviations: PPI, proton pump inhibitor; NSAIDs, nonsteroidal anti-inflammatory drugs.
Other studies corroborate these findings.10,13 One of them found that, “97% of respondents ‘‘strongly agreed/agreed’’ that they were able to decrease the amount of opioids they consume when they also use Cannabis.”13
I am cherry-picking studies, but there are quite a few like this, and the degree of agreement between their findings is quite high.
There are also cross-sectional studies that investigate the other side of the coin – not patients, but healthcare providers. Recently, Michelle, Ryan Bradley, ND, MPH and I investigated healthcare providers who recommend the medical use of Cannabis to their patients. We found that more than 80% reported using Cannabis as an adjunctive therapy to prescription drugs, and more than 70% reported using it as a substitute. When asked what class of drugs they recommend Cannabis as an adjunct to, or a substitute for, “Opioids” was the most frequent class reported. “NSAIDs” were the 4th most frequent class. This study should be published soon.
The evidence is not limited to observational studies however, which are thought to be less rigorous than experimental studies, especially randomized controlled trials. (i.e., RCTs) which are the true standard for measuring the relationship between cause and effect. For example, a 2009 systematic review and meta-analysis of 18 RCTs concluded that Cannabis was “moderately efficacious for treatment of chronic pain”.14 A 2018 systematic review and meta-analysis of 47 RCTs concluded it was, “Unlikely that cannabinoids are highly effective medicines for chronic non-cancer pain.”15 Notice the bar is set higher here - HIGHLY EFFECTIVE as compared to MODERATELY EFFECTIVE in the previous systematic review.
A year earlier, the National Academy of Sciences published a landmark report on the health effects of Cannabis and cannabinoids.16 Among other conclusions in the 441 page report was, “There is conclusive or substantial evidence that cannabis or cannabinoids are effective...For the treatment of chronic pain in adults.”16
Not all the evidence agrees. It rarely does. Scientific investigations are designed to discriminate between the signal the noise. There is a lot of noise in the field of medical Cannabis. The signal, if present, will be refined and measured in time.
To be clear, this post is not intended to be a systematic review of the evidence on Cannabis and pain. I have shamelessly featured my own work. Importantly, there is a vast library of pre-clinical studies I didn’t even mention. An evidence base is built over time and measured by the number and quality of scientific investigations, each with their own methodological advantages and limitations. Keep your eye on upcoming posts for more insight into using Cannabis to treat pain.
Despite the favorable safety profile, dosing and administration of cannabinoids is complicated. The process should be highly individualized and is best supervised by a trained health care professional. For more information, please consider booking a consultation (telephone or in-person) with Dr. Jamie Corroon, ND, MPH.
References
1. Mechoulam R, Ben-Shabat S. From gan-zi-gun-nu to anandamide and 2-arachidonoylglycerol: the ongoing story of cannabis. Natural product reports. 1999;16(2):131-143.
2. Brand EJ, Zhao Z. Cannabis in Chinese Medicine: Are Some Traditional Indications Referenced in Ancient Literature Related to Cannabinoids? Front Pharmacol. 2017;8:108.
3. Mechoulam R, Hanus L. A historical overview of chemical research on cannabinoids. Chem Phys Lipids. 2000;108(1-2):1-13.
4. Bridgeman MB, Abazia DT. Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting. P T. 2017;42(3):180-188.
5. Lee MA. Smoke Signals. 2019.
6. Gaskin DJ, Richard P. The Economic Costs of Pain in the United States. National Academies Press (US); 2011.
7. Understanding the Epidemic | Drug Overdose | CDC Injury Center. 2018; https://www.cdc.gov/drugoverdose/epidemic/index.html.
8. Marijuana. 2019; https://www.dea.gov/factsheets/marijuana.
9. SextonMichelle, CuttlerCarrie, S. F, K. M. A Cross-Sectional Survey of Medical Cannabis Users: Patterns of Use and Perceived Efficacy. http://wwwliebertpubcom/can. 2016.
10. Lucas P, Walsh Z. Medical cannabis access, use, and substitution for prescription opioids and other substances: A survey of authorized medical cannabis patients. The International journal on drug policy. 2017;42:30-35.
11. Corroon JM, Phillips J. A Cross-Sectional Study of Cannabidiol Users. Cannabis and cannabinoid research. 2018.
12. Corroon JM, Jr., Mischley LK, Sexton M. Cannabis as a substitute for prescription drugs - a cross-sectional study. Journal of pain research. 2017;10:989-998.
13. Reiman A, Welty M, Solomon P. Cannabis as a Substitute for Opioid-Based Pain Medication: Patient Self-Report. Cannabis and cannabinoid research. 2017;2(1):160-166.
14. Martin-Sanchez E, Furukawa TA, Taylor J, Martin JL. Systematic review and meta-analysis of cannabis treatment for chronic pain. Pain Med. 2009;10(8):1353-1368.
15. Stockings E, Campbell G, Hall WD, et al. Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions: a systematic review and meta-analysis of controlled and observational studies. Pain. 2018;159(10):1932-1954.
16. National Academies of Sciences E, and Medicine, Division HaM, Practice BoPHaPH, Agenda CotHEoMAERaR. The Health Effects of Cannabis and Cannabinoids. National Academies Press (US); 2017/01/12 2017.
17. Treede RD. The International Association for the Study of Pain definition of pain: as valid in 2018 as in 1979, but in need of regularly updated footnotes. Pain Rep. 2018;3(2).
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