The effectiveness of cannabis-related products to treat chronic pain is surprisingly thin

Evidence behind the effectiveness of cannabis-related products to treat chronic pain is surprisingly thin, according to a new systematic evidence review by researchers at Oregon Health & Science University.

The federally funded review, which will be updated on an ongoing basis, was published today in the Annals of Internal Medicine.

Researchers did find evidence to support a short-term benefit in treating neuropathic pain – caused by damage to peripheral nerves, such as diabetic neuropathy resulting in pain described as burning and tingling, involving two FDA-approved synthetic products with 100% tetrahydrocannabinol, or THC: dronabinol (under the trade name Marinol) and nabilone (Cesamet). Both products also lead to notable side effects including sedation and dizziness, according to the review.

Another product, a sublingual spray of equal parts THC and cannabidiol, or CBD, extracted from the cannabis plant, known as nabiximols, also showed evidence of some clinical benefit for neuropathic pain, although that product is not available in the U.S. This product also led to side effects, such as nausea, sedation and dizziness.

“In general, the limited amount of evidence surprised all of us,” said lead author Marian S. McDonagh, Pharm.D., emeritus professor of medical informatics and clinical epidemiology in the OHSU School of Medicine. “With so much buzz around cannabis-related products, and the easy availability of recreational and medical marijuana in many states, consumers and patients might assume there would be more evidence about the benefits and side effects.

“Unfortunately, there is very little scientifically valid research into most these products,” she said. “We saw only a small group of observational cohort studies on cannabis products that would be easily available in states that allow it, and these were not designed to answer the important questions on treating chronic pain.”

Voters in Oregon, Washington and 20 other states have legalized medical and recreational marijuana, however the researchers found many of the products now available at U.S. dispensaries have not been well studied.

“For some cannabis products, such as whole-plant products, the data are sparse with imprecise estimates of effect and studies had methodological limitations,” the authors write.

This situation makes it difficult to guide patients.

“Cannabis products vary quite a bit in terms of their chemical composition, and this could have important effects in terms of benefits and harm to patients,” said co-author Roger Chou, M.D., director of OHSU’s Pacific Northwest Evidence-based Practice Center. “That makes it tough for patients and clinicians since the evidence for one cannabis-based product may not be the same for another.”

The living review, including a visual abstract summary of the findings, will also be shared on a new web-based tool launched by OHSU and VA Portland Health Care System early this year to help clinicians and researchers evaluate the latest evidence around the health effects of cannabis. Known as Systematically Testing the Evidence on Marijuana, or STEM, the project includes “clinician briefs” to help health care workers translate the clinical implications.

“This new living evidence review is exactly the type of resource clinicians need to clarify for patients the areas of potential promise, the cannabis formulations that have been studied and, importantly, the major gaps in knowledge,” said co-author Devan Kansagara, M.D., M.C.R., professor of medicine in the OHSU School of Medicine and a staff physician at the VA Portland.

Reviewers searched more than 3,000 studies in the scientific literature as of January of this year and landed on a total of 25 with scientifically valid evidence – 18 randomized controlled studies and seven observational studies of at least four weeks.

The effects of cannabis and related products are based on their ability to mimic the body’s own endocannabinoid system. The system is comprised of receptors and enzymes in the nervous system that regulate bodily functions and can affect the sensation of pain. In the evidence review, researchers sorted the types of product into high, comparable and low ratios of THC to CBD and compared their reported benefits and side effects.

Dronabinol and nabilone fit into the high THC to CBD ratio category, with 100% THC (no CBD), showing the most benefit among the products studied, with meta-analysis of the six randomized controlled studies demonstrating statistically valid benefits for easing neuropathic pain compared to a placebo.

“Honestly, the best advice is to talk to your primary care physician about possible treatments for chronic pain,” McDonagh said. “If you want to consider cannabis, you need to talk to your doctor.”

In addition to McDonagh, Chou and Kansagara, co-authors included Benjamin J. Morasco, Ph.D., Jesse Wagner, M.A., Azrah Y. Ahmed, B.A., and Rongwei Fu, Ph.D.

he number and importance of cannabinoid-based medicines is increasing in evidence-based medicine. The efficacy of nabilone and dronabinol has been confirmed in several clinical trials and meta-analyses [27,28]. However, data on safety and AEs are also necessary for the assessment of risk benefit ratios. Here, we present the results of the first systematic review and meta-analysis on the AE profiles of nabilone and dronabinol based on the results of randomized, double blind, placebo-controlled trials.

In case of nabilone, four AEs were meta-analyzed. Drowsiness, dizziness, and dry mouth were more frequent in the patients treated with nabilone than in the placebo group, whereas the frequency of headache was not different in the two groups. In patients treated with dronabinol, more adverse effects could be meta-analyzed.

The frequency of dizziness, dry mouth and headache was significantly higher in the dronabinol groups, whereas in case of nausea, drowsiness and fatigue no significant difference could be observed. Dizziness and dry mouth are common in case of the application of both pharmaceuticals. This might be surprising based on the similar mechanism of action of the two compounds, however, the measures of agonist activities on CB1 and CB2 receptors are different, and both compounds might also act on other targets that also affect adverse effect profiles.

The adverse effects discussed here are diverse, but not severe. In the analyzed clinical trials, 40 different adverse effects were reported for nabilone and 111 for dronabinol; however, the majority of these were not recorded in at least 3 trials that would be sufficient for meta-analysis. In the case of radiotherapy-induced nausea and vomiting, international guidelines recommend the use of serotonin receptor antagonists (e.g., granisetron, ondansetron, tropisetron) and dexamethasone as prophylaxis [29].

In case of chemotherapy-induced nausea and vomiting, the recommendations are more diverse; however, serotonin receptor antagonists and dexamethasone are the most commonly used medications [30]. The long-term use of dexamethasone is related to several adverse events, whereas in the case of serotonin receptor antagonists, the most frequent adverse effects are headache, constipation, weakness and somnolence [31].

Although the side effect profiles of cannabinoids have not been clinically compared with the therapies recommended by guidelines, based on the available evidence, the benefit–risk ratio of cannabinoids does not seem to be inferior. In the case of anorexia associated with weight loss in patients with AIDS, the lack of other pharmaceuticals with confirmed clinical efficacy makes dronabinol an indispensable part of the therapy, and this fact has to be taken into account in the benefit–risk assessment.

Further, in high-quality trials of appropriate patient size, examining the side-effects of dronabinol or nabilone with comparable and more uniform endpoints would allow an assessment of the safety profile of these compounds with a lower risk of bias. Moreover, a considerable amount of trials reporting the same or similar side-effects that can be easily grouped and that are related to different doses of these drugs would enable the assessment of the dose dependency of the side-effects.

reference link : https://www.mdpi.com/1424-8247/15/1/100/htm

More information: Cannabis-Based Products for Chronic Pain. A Systematic Review, Annals of Internal Medicine (2022). DOI: 10.7326/M21-4520 , www.acpjournals.org/doi/10.7326/M21-4520