Evidence is lacking for the effectiveness of cannabis-related products to treat chronic pain, according to a systematic evidence review funded by the Agency for Healthcare Research and Quality of the US Department of Health and Human Services, in the Annals of Internal Medicine.
Reviewers searched more than 3,000 studies in the scientific literature as of January this year and landed on a total of 25 with scientifically valid evidence – 18 randomised controlled studies and seven observational studies of at least four weeks. The review, conducted by researchers at Oregon Health & Science University (OHSU), will be updated on an ongoing basis.
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 (THC): dronabinol (under the trade name Marinol) and nabilone (Cesamet). However, 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 (CBD), extracted from the cannabis plant, known as nabiximols, also showed evidence of some clinical benefit for neuropathic pain. 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 Dr Marian McDonagh, 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.”
In a number of countries across the world, as well as in 22 states of the US, medical and recreational cannabis has been legalised. However, the researchers found many of the products now available at US 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 Dr Roger Chou, director of OHSU's Pacific Northwest Evidence-based Practice Centre. “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 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 healthcare 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 Dr Devan Kansagara, professor of medicine in the OHSU School of Medicine and a staff physician at the VA Portland.
The effects of cannabis and related products are based on their ability to mimic the body’s own endocannabinoid system. The system is composed 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 randomised 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.”
Study details
Cannabis-Based Products for Chronic Pain – A Systematic Review
Marian S McDonagh, Benjamin J Morasco, Jesse Wagner, Azrah Y Ahmed, Rongwei Fu, Devan Kansagara, and Roger Chou.
Published in Annals of Internal Medicine on 1 June 2022
Background:
Contemporary data are needed about the utility of cannabinoids in chronic pain.
Purpose:
To evaluate the benefits and harms of cannabinoids for chronic pain.
Data Sources:
Ovid MEDLINE, PsycINFO, EMBASE, the Cochrane Library, and Scopus to January 2022.
Study Selection:
English-language, randomiSed, placebo-controlled trials and cohort studies (≥1 month duration) of cannabinoids for chronic pain.
Data Extraction:
Data abstraction, risk of bias, and strength of evidence assessments were dually reviewed. Cannabinoids were categoriSed by THC-to-CBD ratio (high, comparable, or low) and source (synthetic, extract or purified, or whole plant).
Data Synthesis:
Eighteen randomised, placebo-controlled trials (n = 1740) and 7 cohort studies (n = 13 095) assessed cannabinoids. Studies were primarily short term (1 to 6 months); 56% enrolled patients with neuropathic pain, with 3% to 89% female patients. Synthetic products with high THC-to-CBD ratios (>98% THC) may be associated with moderate improvement in pain severity and response (≥30% improvement) and an increased risk for sedation and are probably associated with a large increased risk for dizziness. Extracted products with high THC-to-CBD ratios (range, 3:1 to 47:1) may be associated with large increased risk for study withdrawal due to adverse events and dizziness. Sublingual spray with comparable THC-to-CBD ratio (1.1:1) probably is associated with small improvement in pain severity and overall function and may be associated with large increased risk for dizziness and sedation and moderate increased risk for nausea. Evidence for other products and outcomes, including longer-term harms, were not reported or were insufficient.
Limitation:
Variation in interventions; lack of study details, including unclear availability in the United States; and inadequate evidence for some products.
Conclusion:
Oral, synthetic cannabis products with high THC-to-CBD ratios and sublingual, extracted cannabis products with comparable THC-to-CBD ratios may be associated with short-term improvements in chronic pain and increased risk for dizziness and sedation. Studies are needed on long-term outcomes and further evaluation of product formulation effects.
Primary Funding Source:
Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services. (PROSPERO: CRD42021229579)
Full study in Annals of Internal Medicine (Open Access)
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