Cannabis and Chronic Pain: Is It an Effective Treatment?
After reviewing a large number of published clinical studies on the use of various forms of cannabis (marijuana) to treat neuropathic pain, the authors of a recent study concluded that there was limited evidence to suggest any beneficial effectiveness. In addition, there was insufficient evidence that cannabis was useful in treating other types of chronic pain.
Little comprehensive and peer-reviewed information exists about the benefits and harms of using cannabis to treat chronic pain. This study was a systematic literature review by authors from the VA Portland (Oregon) Health Care System and the Oregon Health and Science University. Its goal was to assess the efficacy of cannabis for treating chronic pain and to assess the short- and long-term physical and mental health effects of cannabis use in both chronic pain and general patient populations.
The report can be accessed at: Nugent, SM, et al. “The effects of cannabis among adults with chronic pain and an overview of general harms. A systematic review.” Annals of Internal Medicine, DOI: 10.7326/M17-0155.
The study was funded by U.S. Department of Veterans Affairs.
Criteria for Study Selection
The authors’ method was to search for studies in MEDLINE, Cochrane Database of Systematic Reviews, and several other sources from database inception to March 2017. Search criteria included any study in the English language which assessed the effect on non-pregnant adults of plant-based cannabis preparations or whole plant extracts such as nabiximols, an oro-mucosal spray containing the non-synthetic plant-based extract. They did not include studies which evaluated synthesized cannabinoids such as dronabinol and nabilone because these are not available in marijuana dispensaries.
Plant-based cannabis preparations included any preparation of the cannabis plant itself (cannabis cigarettes, cannabis oils) or cannabis plant extracts to capture the variety of products available in U.S. dispensaries.
The efficacy of cannabis for treating chronic pain was assessed according to pain outcomes, reported in both controlled clinical trials and cohort studies. Assessments were also made on the general harms from cannabis use, both from studies of the general population and populations with chronic pain.
Two investigators independently abstracted study characteristics and assessed study quality, and the investigator group graded the overall strength of evidence using standard criteria. Each trial was assessed as having low, high, or unclear risk of bias (ROB) for the pain outcome, using a tool developed by the Cochrane Collaboration.
For the pain studies, the authors did a study-level meta-analysis of the proportion of patients experiencing clinically significant pain relief (defined as greater or equal to 30% relief).
Overall, 13,674 titles were reviewed. From this total, the authors selected 13 systemic reviews and 62 primary studies. For those addressing treatment of chronic pain, they identified 22 random controlled trials (RCTs) from published systematic reviews and an additional 5 RCTs and 3 cohort studies not included in prior reviews.
The methods for pain assessment in the reviewed studies were visual analog scale (VAS) from 0-100 mm and a numerical rating scale (NRS) from 0-10 with 0 = no pain and 10 = worst pain. Some studies identified subjects who had significant improvements in pain intensity defined as equal to or greater than 30% pain reduction or approximately 2 points on the NRS and 20 mm on VAS.
Among the chronic pain studies, 13 examined the effects of cannabis-based preparation in neuropathic pain. Study subjects had central or peripheral neuropathic pain related to various health conditions. The authors found low evidence that cannabis may alleviate neuropathic pain in some patients. The studies generally did not find significant between-group differences on continuous pain scales, but a higher proportion of patients had significant pain relief up to several months later.
Across nine studies, cannabis-treated patients were more likely to report at least 30% improvement in pain (risk ratio 1.43), indicating about one-and-a-half times better improvement compared to controls. Most studies were small; few reported outcomes beyond 2-3 weeks, and none reported long-term outcomes.
Cannabis preparations used in the studies with typical dosing were as follows:
- Smoked THC (tetra-hydrocannabinol), 4%, dose = 1 cigarette/day for 12 days
- Smoked THC, 4%, dose = 4 smoking sessions/day for 5 days
- Nabiximols (THC oro-mucosal spray), dose = approximately 12, 24, or 48 sprays/day for at least 2 weeks
- Vaporized THC, 7%, 4%, or 1%, 4-hour observation after one dose
The largest study was of RCT protocol involving 246 subjects with peripheral neuropathic pain. For the cannabis group, nabiximols were self-titrated up to a maximum dosage of 24 sprays per day. The placebo group was given a similar regimen. Seventy-nine subjects completed the study in the nabiximols group and 94 in the placebo group. The nabiximols group had both responders and non-responders. Those who responded positively to the nabiximols intervention had a significant decrease in pain with an odds ratio of 1.97 (approximately two times greater than control). However, among all participants including non-responders to nabiximols, the decrease in the NRS pain score did not reach statistical or clinical significance.
The second largest study, also RCT protocol, included 55 patients with HIV-associated sensory neuropathy who were randomly assigned to smoke either 3.56% THC cigarettes or a placebo three times daily for five days. Thirteen (52%) completed the study in the THC group and six (24%) in the placebo group. The authors stated that there was a clinically significant reduction in pain in the THC group.
There was a one-year prospective cohort study (n=431) of patients with chronic non-cancer pain. Cannabis users had a reduction in average pain intensity using a visual analogue scale (from 0 to 10) which was stable across four time points over the year, but the change was small and not clinically significant.
Adverse events reported in chronic pain studies
Two systematic reviews evaluating cannabis for chronic pain suggest that cannabis may be associated with a higher risk of short-term, non-serious adverse effects. Most reported adverse events were mild, such as dizziness and light-headedness. Other adverse events reported were:
- Dry mouth
- Loss of balance
Some were serious, such as suicide attempts, paranoia, and agitation.
Harms in the general population
The authors found moderate-strength evidence from two well-designed studies suggesting that light-to-moderate cannabis smoking does not adversely affect lung function over 20 years in young adults. Limited data on the effects of heavy use, however, suggest a possible deleterious effect on lung function over time.
Motor vehicle accidents in the general population
The authors stated that moderate-strength evidence from a recent meta-analysis of 21 multinational observation studies suggested that acute cannabis intoxication is associated with a moderate increase in collision risk (approximately 1.4 times greater) compared with no cannabis use.
Authors’ Discussion and Conclusion
The authors found limited evidence that cannabis preparations may alleviate neuropathic pain and insufficient evidence in populations with other types of chronic pain. The authors emphasize that clinicians will need to engage in evidence-based discussions with patients managing chronic pain who are using or requesting to use cannabis.
Currently, evidence-based, non-pharmacologic, and non-opioid pharmacologic therapies are the preferred initial methods for treating chronic pain. In terms of any comparison with opioids, the scale and severity of adverse events, including death seen with opioids, have not been described with cannabis. However, no studies have directly compared cannabis with opioids, and no good quality data exists on how cannabis use affects opioid use.
In conclusion, the statement by the authors is as follows: “Limited evidence suggests that cannabis may alleviate neuropathic pain in some patients, but insufficient evidence exists for other types of chronic pain."
Richard L. Wynn, BS Pharm, PhD, is professor of pharmacology at the Baltimore College of Dental Surgery, Dental School, University of Maryland Baltimore.
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