Cannabis-related products demonstrate short-term reduction in chronic pain
OHSU researchers find thin evidence in federally funded systematic review of scientific literature
Peer-Reviewed PublicationEvidence 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.
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.
The project was funded by Agency for Healthcare Research and Quality of the U.S. Department of Health and Human Services, contract number 75Q80120D00006. Statements in the report should not be construed as endorsement by the AHRQ or the Department of Health and Human Services.
JOURNAL
Annals of Internal Medicine
METHOD OF RESEARCH
Literature review
SUBJECT OF RESEARCH
People
ARTICLE TITLE
Cannabis-Based Products for Chronic Pain. A Systematic Review
ARTICLE PUBLICATION DATE
6-Jun-2022
Some cannabis products associated with short-term chronic pain improvements, but side effects a concern
1. Some cannabis products associated with short-term chronic pain improvements, but side effects a concern
Abstract: https://www.acpjournals.org/doi/10.7326/M21-4520
Editorial: https://www.acpjournals.org/doi/10.7326/M22-1512
URLs go live when the embargo lifts
A review of 25 trials and studies assessing cannabinoids has found that oral synthetic cannabis products with high THC-to-CBD ratios and extracted cannabis products with comparable tetrahydrocannabinol (THC)-to-cannabidiol (CBD) ratios were associated with moderate, short-term chronic pain improvements. However, these products were associated with higher risks for adverse events and few benefits in overall functioning. The findings are published in Annals of Internal Medicine.
Approximately 100 million Americans are living with chronic pain. While opioids are frequently prescribed to manage chronic pain, they demonstrate little affect on pain overall and are associated with significant adverse effects. Cannabinoid products are a potential alternative and can come from multiple sources, including synthetic, extract, or whole plant. The term “cannabinoid” references compounds that are active in cannabis, such as THC and CBD. These compounds have previously demonstrated pain-relief properties that vary depending on the ratio of THC to CBD.
Researchers from Oregon Health & Science University reviewed 18 randomized, placebo-controlled trials, comprising 1,740 participants, and 7 cohort studies, comprising 13,095 participants, to evaluate the benefits and harms of cannabinoids for chronic pain. They found that synthetic products with high THC-to-CBD ratios were associated with moderate improvement in pain severity and response but were also associated with an increased risk for sedation and dizziness. The authors also found that small improvements in overall function were demonstrated for products with comparable THC-to-CBD ratios, but no improvements were demonstrated for products with high THC-to-CBD ratios. However, they determined that evidence for whole-plant products, CBD, and other cannabinoids was limited by serious imprecision and lack of ability to assess consistency and study methodological limitations. The authors also note that reviewed studies did not evaluate harm outcomes including psychosis, cannabis use disorder, and cognitive deficits, and studies did not include patients who were at higher risk for harms.
An accompanying editorial by authors from the University of Michigan Medical School advises clinicians to be willing to provide compassionate guidance to patients who use cannabis products by using a strategy of pragmatism and knowledge of patient experience, known cannabinoid effects, and harm reduction. The authors highlight that this review can offer information to clinicians on routes of administration, the effects of CBD versus THC, dosing, and potential adverse effects.
Media contacts: For an embargoed PDF or to speak with editorialist Christine Laine, MD, MPH, please contact Angela Collom at acollm@acponline.org. To speak with the lead author Marian S. McDonagh, PharmD, please email Erik Robinson at robineri@ohsu.edu.
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2. New co-prescription of opioids and benzodiazepines decreased by nearly 60% between 2016 and 2019
Abstract: https://www.acpjournals.org/doi/10.7326/M21-4656
URL goes live when the embargo lifts
A study of national opioid and benzodiazepine prescription trends found that number of patients with concurrent opioids and benzodiazepines declined significantly since 2016, particularly among young adults. The research report is published in Annals of Internal Medicine.
Opioids and benzodiazepines can lead to synergistic respiratory depression when taken together, which increases overdose risk. The percentage of all opioid overdose deaths involving benzodiazepines increased from 8.7% in 1999 to 21% in 2017, and benzodiazepines were involved in 1 out of every 3 prescription opioid overdose deaths in 2017.
Authors from the Centers for Disease Control and Prevention (CDC) and Boston Medical Center studied data from a national database containing prescription records from a sample of approximately 49,900 retail pharmacies that dispense nearly 92% of retail pharmacy prescriptions in the United States to examine trends in patients receiving concurrent opioid and benzodiazepine prescriptions from 2016 to 2019 at national and state levels. They found that the number of patients newly initiated with concurrent prescriptions declined 59 percent from 2016 to 2019 and only accounted for 28.5 percent of total patients with concurrent prescriptions in 2019, indicating that far fewer patients started treatment with opioids and benzodiazepines together. According to the authors, their findings highlight the need for continued public health and clinical actions, including greater adherence to evidence-based prescribing guidelines, more patient education, and alternative pain-management options. They add that these data highlight the need for evidence-based protocols to safely de-prescribe opioids and/or benzodiazepines for patients already exposed.
Media contacts: For an embargoed PDF or to speak with someone from ACP, please contact Angela Collom at acollom@acponline.org. To speak with the corresponding author, Kun Zhang, PhD, please contact Helen Kingery at wzq8@cdc.gov.
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JOURNAL
Annals of Internal Medicine
METHOD OF RESEARCH
Systematic review
SUBJECT OF RESEARCH
People
ARTICLE TITLE
Cannabis-Based Products for Chronic Pain
ARTICLE PUBLICATION DATE
7-Jun-2022
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