News Release

Some cannabis products associated with short-term chronic pain improvements, but side effects a concern

Embargoed news from Annals of Internal Medicine

Peer-Reviewed Publication

American College of Physicians

1. Some cannabis products associated with short-term chronic pain improvements, but side effects a concern



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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 To speak with the lead author Marian S. McDonagh, PharmD, please email Erik Robinson at


2. New co-prescription of opioids and benzodiazepines decreased by nearly 60% between 2016 and 2019


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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 To speak with the corresponding author, Kun Zhang, PhD, please contact Helen Kingery at



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