ACP’s Best Practice Advice addresses use of cannabis, cannabinoids for chronic noncancer pain

American College of Physicians

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NEW ORLEANS April 4, 2025 – The American College of Physicians (ACP) has issued Best Practice Advice for clinicians whose patients are considering or using cannabis or cannabinoids for management of chronic, noncancer pain. Cannabis or Cannabinoids for the Management of Chronic Noncancer Pain: Best Practice Advice From the American College of Physicians, was published today in Annals of Internal Medicine. 

 

ACP’s Best Practice Advice paper is intended to inform clinicians about the evidence regarding the benefits and harms of cannabis or cannabinoids in the management of chronic noncancer pain and to provide advice for clinicians counseling patients seeking to use cannabis or cannabinoids for chronic noncancer pain. 

 

Cannabis use for medicinal purposes has grown among patients with chronic noncancer pain. When referring to any product derived from the plant, many use the term cannabis, but the term has become interchangeable with colloquial terms such as marijuana, weed, and pot. As of 2024, 24 states in the U.S. and the District of Columbia have legalized cannabis for adult recreational and medical use, and it is legal for medical use only in an additional 14 states. 

 

In its Best Practice Advice ACP says clinicians should: 

 

• Counsel patients about the benefits and harms of cannabis or cannabinoids when patients are considering whether to start or continue to use cannabis or cannabinoids to manage their chronic noncancer pain.  

• Counsel the following subgroups of patients that the harms of cannabis or cannabinoid use for chronic noncancer pain are likely to outweigh the benefits: 

  • Young adult and adolescent patients 

  • Patients with current or past substance use disorders 

  • Patients with serious mental illness  

  • Frail patients and those at risk of falling  

• Advise against starting or continuing to use cannabis or cannabinoids to manage chronic noncancer pain in patients who are pregnant or breastfeeding or actively trying to conceive. 

• Advise patients against the use of inhaled cannabis to manage chronic noncancer pain. 

 

“This Best Practice Advice is important for practicing physicians when counseling our patients on the potential use of cannabis and cannabinoids to treat their chronic noncancer pain,” said Isaac O. Opole, President, ACP. “As the use of cannabis for medicinal purposes grows it’s critical to open that dialogue and review the emerging evidence related to benefits and harms. We need to raise awareness and get the word out to ensure that patients have the information they need to make informed decisions.” 

 

For many patients, evidence suggests that the known harms of cannabis and cannabinoid use outweigh the potentially small degree of benefit to ease chronic noncancer pain. Additionally, cannabis can be addictive, even if being used to manage chronic noncancer pain. It’s also difficult to apply the information from clinical studies to practice in the U.S. because the potency (delta-9 tetrahydrocannabinol or THC content) of products in dispensaries is typically far higher than that used in studies. Another challenge is that in most U.S. states, patients will obtain cannabis for chronic pain through a dispensary with less medical oversight than they would receive for FDA-approved medications.   

Clinicians are best positioned to provide evidence-based information about the benefits and harms most relevant to an individual patients’ needs and comorbidities so that patients can make an informed decision about starting or continuing cannabis or cannabinoid use for chronic noncancer pain.  For most patients, common treatments and analgesic medications should be recommended first given the limited evidence of small benefit and the known harms associated with cannabis and cannabinoid products.     

ACP has also published a position paper where it recommends a public health approach to address the legal, medical, and social complexities of cannabis use. 

 

This Best Practice Advice is based on a review and assessment of scientific work including a living, systematic review on cannabis and cannabinoid treatments for chronic noncancer pain, a series of living systematic reviews, as well as additional evidence from primary studies. 

 

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About the American College of Physicians 
The American College of Physicians is the largest medical specialty organization in the United States with members in more than 172 countries worldwide. ACP membership includes 161,000 internal medicine physicians, related subspecialists, and medical students. Internal medicine physicians are specialists who apply scientific knowledge and clinical expertise to the diagnosis, treatment, and compassionate care of adults across the spectrum from health to complex illness. Follow ACP on X, Facebook, Instagram, Threads, and LinkedIn. 

 

ACP Media Contact: Andrew Hachadorian, (215) 351-2514, AHachadorian@acponline.org 

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Journal

Annals of Internal Medicine

DOI

10.7326/ANNALS-24-03319 

Method of Research

News article

Subject of Research

People

Article Title

Cannabis or Cannabinoids for the Management of Chronic Non-Cancer Pain: Best Practice Advice from the American College of Physicians

Article Publication Date

4-Apr-2025

 

Beyond photorespiration: A systematic approach to unlocking enhanced plant productivity

New research from GAIN4CROPS project provides critical insights into overcoming one of agriculture's most costly inefficiencies.

INsociety

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A groundbreaking study published in Science Advances has revealed promising strategies to significantly improve crop yields by addressing photorespiration, a metabolic process that can reduce productivity by up to 36% in some crops. Researchers from the University of Groningen and Heinrich Heine University Düsseldorf, working as part of the GAIN4CROPS project (gain4crops.eu), have evaluated several alternative pathways that could help overcome this major agricultural bottleneck.

Photorespiration occurs when the enzyme RuBisCO, essential for photosynthesis, reacts with oxygen instead of carbon dioxide, resulting in substantial losses of fixed carbon and energy. This inefficiency costs the global agricultural sector billions in lost crop productivity annually.

"Our work shows that overcoming photorespiration through engineered pathways can provide a dual benefit: increasing carbon fixation while reducing energy losses," said Prof. Heinemann from the University of Groningen, "This has significant implications for the development of crops that are not only more productive but also better adapted to the changing climate and growing global food demands."

The study employed advanced mathematical models to analyze twelve alternative pathways designed to bypass or optimize photorespiration. The researchers classified these pathways based on their carbon-fixing abilities and identified which approaches offer the greatest potential improvements in different environmental conditions.

Key findings include:

• Carbon-fixing alternative pathways showed the most promise, offering up to 20% more carbon export compared to conventional photorespiration
• The TaCo pathway, developed in another EU-funded project called FutureAgriculture and now used in projects such as GAIN4CROPS and CROP4CLIMA, demonstrated substantial potential for yield improvement
• Environmental factors such as light intensity and CO2 availability significantly influence the effectiveness of different pathways
• Carbon-fixing pathways achieve optimal productivity under both high light and CO2-limited conditions

The research also provides new insights that could help explain previous experimental observations and guides future efforts to engineer crops with reduced photorespiration losses.

"With the ability to more rationally engineer alternative photorespiratory pathways into suitable crops and identify their optimal growing conditions, our work will hopefully contribute to realizing the maximum impact of alternative photorespiratory pathways for improving crop yields," noted Prof. Weber, coordinator of the GAIN4CROPS project from the Heinrich Heine University Düsseldorf.

Next steps include further optimization of the alternative pathways and application to crops with the greatest potential for yield improvement. These advancements could play a crucial role in addressing global challenges such as food security and climate change adaptation.

The full study, titled “Alternatives to photorespiration: A system-level analysis reveals mechanisms of enhanced plant productivity” is available in open access in Science Advances (https://www.science.org/doi/10.1126/sciadv.adt9287).

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Journal

Science Advances

DOI

10.1126/sciadv.adt9287 

Subject of Research

Not applicable

Article Title

Alternatives to photorespiration: A system-level analysis reveals mechanisms of enhanced plant productivity

 

How a small number of mutations can fuel outbreaks of western equine encephalitis virus

Study shows how spike protein changes determine the risk of viral outbreaks

Harvard Medical School

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New research shows how small shifts in the molecular makeup of a virus can profoundly alter its fate. These shifts could turn a deadly pathogen into a harmless bug or supercharge a relatively benign virus, influencing its ability to infect humans and cause dangerous outbreaks.

This is the latest finding in a series of studies led by Jonathan Abraham, associate professor of microbiology in the Blavatnik Institute at Harvard Medical School, and his team that aim to understand the risk of western equine encephalitis virus and related viruses. The work, which was supported by federal funding, is published in Cell on April 4.

The findings, the research team said, offer important insights that could help researchers and public health experts better anticipate the likelihood of future outbreaks.

Historically, WEEV has caused large and dangerous outbreaks of encephalitis (a serious type of brain inflammation) among humans and horses throughout the Americas.

The virus circulates mainly between mosquitoes and birds. Since the turn of the century, WEEV has disappeared as a pathogen in North America. In South America, the virus occasionally spilled over to sicken small numbers of humans and mammals. However, in 2023, WEEV caused the first major human outbreak in four decades in South America, involving thousands of horses and over a hundred confirmed human cases.

How did the virus lose its ability to infect humans in North America? Why did the virus persist as a pathogen in South America and re-emerge to cause a major outbreak? The secret lies in alterations in its molecular makeup, the new study found.

Using an advanced imaging technique, the researchers determined how the spike proteins on the surface of WEEV strains isolated over the past century interact with a type of cell receptor known as PCDH10 that is shared by humans and birds.

The virus enters its host and causes infection by attaching one of its spike proteins to a receptor on the surface of the host cell. In order to cause infection, the spike protein and receptor need to fit each other, like matching pieces of a jigsaw puzzle.

In a strain from 1958, when deadly WEEV outbreaks happened regularly, the virus was a good fit for both human and bird cell receptors.

However, a North American WEEV strain isolated from mosquitoes in California in 2005 was a good fit for bird cell receptors but not for mammals.

The researchers found that a single mutation in the virus’s spike protein was enough to prevent it from attaching to human and horse cells. The mutation, however, still allowed the virus to enter and infect cells using the bird receptor.

Strains isolated in South America over the past century, including the 2023–2024 outbreak strains, had never acquired the single mutation that would prevent them from attaching to the human and horse cell receptors.

The researchers also observed that a single change in the viral spike protein enabled WEEV strains to attach to a different receptor called VLDLR, found on mammalian brain cells. This same receptor is shared by WEEV’s cousin, eastern equine encephalitis virus (EEEV), which is the most virulent alphavirus and has continued to cause outbreaks in North America. In the past, highly virulent, ancestral forms of WEEV were capable of invading host cells through VLDLR.

Notably, when researchers blocked this key receptor using a decoy VLDLR protein, animals infected with the older, more dangerous WEEV strain were protected against the deadly brain inflammation caused by these virulent strains.

The new findings offer critical clues for pandemic preparedness because they provide insights on the first major human outbreak of WEEV in four decades in South America and could help efforts to monitor North American WEEV strains for their potential to cause large outbreaks.

Additionally, the virus’s rapid ability to shift from a harmless reservoir in insects and wild birds to a dangerous human pathogen highlights the importance of surveillance efforts to monitor for potential outbreaks and emerging diseases.

“The more we understand about this important group of emerging viruses before a serious threat emerges, the better,” Abraham said.

 

Authorship, Funding, Disclosures

Additional authors include Xiaoyi Fan, Wanyu Li, Jessica Oros, Jessica A. Plante, Brooke M. Mitchell, Jesse S. Plung, Himanish Basu, Sivapratha Nagappan-Chettiar, Joshua M. Boeckers, Laurentia V. Tjang, Colin J. Mann, Vesna Brusic, Tierra K. Buck, Haley Varnum, Pan Yang, Linzy M. Malcolm, So Yoen Choi, William M. de Souza, Isaac M. Chiu, Hisashi Umemori, Scott C. Weaver, and Kenneth S. Plante.

This work was supported by NIH awards R01 AI182377, T32AI700245, T32GM144273, T32GM008313, T32AG000222-33, R24 AI120942, T32AG000222-32, and R01 MH125162; the Jackson-Wijaya Fund; Wellcome Trust grant 226075/Z/22/Z; a Burroughs Wellcome award; a Vallee Scholar award; a Smith Family Foundation Odyssey award; a Charles E.W. Grinnell Trust award; and a G. Harold and Leila Y. Mathers Foundation award. Cryo-EM data were collected at the Harvard Cryo-EM Center for Structural Biology at Harvard Medical School.

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Journal

Cell

DOI

10.1016/j.cell.2025.03.029 

Method of Research

Experimental study

Subject of Research

Cells

Article Title

Molecular basis for shifted receptor recognition by an encephalitic arbovirus

Article Publication Date

4-Apr-2025

 

Research uncovers hidden spread of one of the most common hospital-associated infections

University of Utah Health

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image: 

A health care provider cleans their hands. Hand hygiene is a crucial measure to prevent the invisible spread of C. difficile and other infections.

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Credit: Charlie Ehlert / University of Utah Health

Key Points:

• C. difficile is one of the most common and contagious hospital-acquired infections.
• Research has found that C. diff spreads more than three times more than previously thought.
• C. diff can spread covertly from surface to surface and remain undetected for weeks until it infects a patient.

IMPACT: The results could spur more rigorous preventive measures that stop hidden spread of the disease.

One of the most common health care-associated infections spreads within intensive care units (ICUs) more than three times more than previously thought, new research has found.

Clostridium difficile infection—commonly called C. diff—causes diarrhea, abdominal pain, and fever and is lethal in about 6% of cases in the U.S. The disease is highly contagious, but in previous research, direct patient-to-patient transmission seemed to occur rarely. Now, by tracking the bacterium through the hospital environment, rather than on patients alone, scientists have uncovered previously undetected movement of C. diff bacteria through hospital settings.

“There's a lot going on under the hood that we're just not seeing,” says Michael Rubin, MD, PhD, epidemiologist and infectious diseases specialist in the Spencer Fox Eccles School of Medicine at the University of Utah and senior author on the study. “And if we ignore that, then we’re potentially putting patients at unnecessary risk.”

The results are published in JAMA Network Open.

 

Bacterial movement within the environment is common

To track infections throughout the health care setting, the researchers sampled for C. diff from nearly 200 patients across two intensive care units (ICUs), as well as collecting thousands of samples from hospital room surfaces and health care providers’ hands.

The researchers used whole genome DNA sequencing to precisely track bacterial movement. Different bacterial samples have genetic differences, which the researchers measured to track movement of C. diff around health care facilities. The team was even able to use these differences to determine if two bacterial samples came from the same patient, rather than being acquired independently from a source outside the hospital.

The team detected the bacteria in 10% of patient ICU stays—either on the patient’s body or in their immediate room environment. And in most of those cases, the bacteria were genetically identical to those found in another patient or another patient’s room, suggesting that the bacteria originated from the same patient rather than coming from two different sources.

“We find about the same amount of patient-to-patient transmission as previous studies,” explains Lindsay Keegan, PhD, research associate professor in epidemiology at U of U Health and first author on the study. “But what we find that’s novel is that there is a lot more movement of C. diff between surfaces, from surface-to-patient, and from patient-to-surface than previously found.”

 

Revealing long-term spread

By simultaneously tracking different bacterial varieties on patients, health care providers’ hands, and in the environment, the researchers uncovered cases of potential transmission that wouldn’t have been caught with other methods.

Notably, the team discovered that for more than half of potential transmission events, the two patients involved were never even in the hospital at the same time—sometimes being separated by weeks. The key to this paradox is the exceptional hardiness of C. diff: the bacteria can survive for a long time outside the body, withstanding common antibacterial measures such as alcohol-based cleansers. Bacteria from one person could be inadvertently transferred to surfaces in a different room, where they could lie in wait for another patient, undetected.

Importantly, not all C. diff bacteria cause disease, and most of the C. diff spread the researchers observed involved harmless bacterial varieties. However, the researchers say that the spread of non-disease-causing C. diff suggests that similar transmission of disease-causing C. diff could be going undetected.

 

How to prevent infection

The researchers say that they hope their results lead to stronger precautions to prevent the spread of disease within hospitals.

“What I'm hoping we get from this paper is that health care providers put a greater emphasis on infection prevention measures and adhere to them as much as they possibly can,” Rubin says. Using personal protective equipment such as gloves and gowns, as well as practicing rigorous hand hygiene, are crucial, he adds. “Those are the measures that can help interrupt this type of invisible transmission.”

 

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The results published in JAMA Network Open as “Environmental and Health Care Personnel Sampling and Unobserved Clostridium difficile Transmission in ICU.”

The study was funded by the National Institutes of Health / National Institute of Allergy and Infectious Diseases grant 1K01AI159519 and the Centers for Disease Control and Prevention grants 5U01CK000585 and HHSD-200-2011-42039. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Keegan reported receiving grants from the US Centers for Disease Control and Prevention (CDC) Center for Forecasting and Outbreak Analytics outside the submitted work. Karim Khader, PhD, reported receiving grants from the Department of Veterans Affairs (VA) and bioMerieux outside the submitted work. Rubin reported receiving grants from the CDC and the VA outside the submitted work.

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Journal

JAMA Network Open

DOI

10.1001/jamanetworkopen.2025.2787 

Method of Research

Observational study

Subject of Research

People

Article Publication Date

4-Apr-2025

COI Statement

Dr Keegan reported receiving grants from the US Centers for Disease Control and Prevention (CDC) Center for Forecasting and Outbreak Analytics outside the submitted work. Dr Khader reported receiving grants from the Department of Veterans Affairs (VA) and bioMerieux outside the submitted work. Dr Rubin reported receiving grants from the CDC and the VA outside the submitted work. No other disclosures were reported.

 

Exposure to wildfire smoke linked with worsening mental health conditions

Harvard T.H. Chan School of Public Health

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Key points:

• Short-term exposure to fine particulate air pollution (PM2.5) from a wildfire may increase the risk of emergency department visits for mental health conditions, especially for women, youth, racial minorities, and Medicaid enrollees.
• The study is among the first to examine the relationship between wildfire-specific PM2.5 and mental health.
• According to the researchers, the findings highlight the need for targeted interventions to prevent and address increased mental health distress during wildfire seasons, especially for vulnerable populations.

Boston, MA—Exposure to fine particulate air pollution (PM2.5) from wildfire smoke was associated with increased visits to emergency departments (ED) for mental health conditions, according to a new study led by researchers at Harvard T.H. Chan School of Public Health.

“Wildfire smoke isn’t just a respiratory issue—it affects mental health, too,” said corresponding author Kari Nadeau, John Rock Professor of Climate and Population Studies and chair of the Department of Environmental Health. “Our study suggests that—in addition to the trauma a wildfire can induce—smoke itself may play a direct role in worsening mental health conditions like depression, anxiety, and mood disorders.”

The study will be published April 4 in JAMA Network Open.

The study is the first to isolate the short-term impact of wildfire-specific PM2.5, offering more precise insights into its impacts on mental health. A growing body of research suggests that PM2.5 may influence mental health outcomes, but few studies have investigated the effects of wildfire-specific PM2.5. Most studies of wildfire-specific PM2.5 have focused on its relationship to respiratory and cardiovascular outcomes.

The researchers analyzed data on wildfire-specific PM2.5 levels and emergency department visits for mental health conditions throughout California between July and December 2020, a period covering the state’s most severe wildfire season on record. Daily wildfire-specific PM2.5 levels and visits to the ED for mental health conditions—including psychoactive substance use disorders, psychotic disorders, mood-affective disorders, depression, and anxiety—were ascertained for each zip code in the state.

Throughout the study period, there were 86,588 mental health ED visits. The average daily concentration of wildfire-specific PM2.5 was 6.95 micrograms per cubic meter of air (μg/m3), a level that rose to 11.9 μg/m3 during peak wildfire months and to 24.9 μg/m3 during the highest peak in September. 

The study found that exposure to wildfire smoke substantially increased mental health ED visits. A 10 μg/m3 increase in wildfire-specific PM2.5 was linked to a higher number of visits, including for depression, anxiety, and other mood-affective disorders, for up to seven days post-exposure. Women, children and young adults, Black and Hispanic individuals, and Medicaid enrollees showed the highest risk of mental health ED visits from exposure to wildfire-specific PM2.5.

“The disparities in impact by race, sex, age, and insurance status suggest that existing health inequities may be worsened by wildfire smoke exposure,” added lead author YounSoo Jung, research associate in the Department of Environmental Health. “We need to make sure everyone has access to mental health care during wildfire seasons, particularly the most vulnerable groups and particularly as wildfires become more frequent and severe as a result of climate change.”

Other Harvard Chan authors included Mary Johnson and Caleb Dresser.

The study was supported by the National Heart, Lung, and Blood Institute (grant P01HL152953).

“PM2.5 from 2020 California Wildfires and Mental Health-Related Emergency Department Visits,” YounSoo Jung, Mary M. Johnson, Marshall Burke, Sam Heft-Neal, Melissa L. Bondy, R. Sharon Chinthrajah, Mark R. Cullen, Lorene Nelson, Caleb Dresser, Kari C. Nadeau, JAMA Network Open, April 4, 2025, doi: 10.1001/jamanetworkopen.2025.3326

Visit the Harvard Chan School website for the latest news and events from our Studio.

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Harvard T.H. Chan School of Public Health is a community of innovative scientists, practitioners, educators, and students dedicated to improving health and advancing equity so all people can thrive. We research the many factors influencing health and collaborate widely to translate those insights into policies, programs, and practices that prevent disease and promote well-being for people around the world. We also educate thousands of public health leaders a year through our degree programs, postdoctoral training, fellowships, and continuing education courses. Founded in 1913 as America’s first professional training program in public health, the School continues to have an extraordinary impact in fields ranging from infectious disease to environmental justice to health systems and beyond.

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Journal

JAMA Network Open

DOI

10.1001/jamanetworkopen.2025.3326 

Method of Research

Observational study

Subject of Research

Not applicable

Article Title

PM2.5 from 2020 California Wildfires and Mental Health-Related Emergency Department Visits

Article Publication Date

4-Apr-2025

Fine particulate matter from 2020 California wildfires and mental health–related emergency department visits

JAMA Network Open

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About The Study: 

Wildfire smoke exposure was associated with significantly increased odds of subsequent emergency department visits for mental health conditions in this cross-sectional study, with varying lag times for different subconditions and demographic groups. Health care professionals and systems should prepare for a possible increase in demand for mental health–related emergency services during wildfire events.

Corresponding Author: To contact the corresponding author, Kari C. Nadeau, MD, PhD, email knadeau@hsph.harvard.edu.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2025.3326)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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About JAMA Network Open: JAMA Network Open is an online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication. 

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Journal

JAMA Network Open