Category: From Newswise – Addiction

Newswise — New research led by UCLA Health has found a drug that treats insomnia works to prevent the addictive effects of the morphine opioids in mice while still providing effective pain relief.  

The study, published in the journal Nature Mental Health, concluded that suvorexant, which blocks brain receptors for a neurotransmitter called hypocretin, prevents opioid addiction. At high doses in humans, suvorexant induces sleep and is used to treat insomnia. But sleep was not induced, and behavioral alertness was maintained, at the much lower doses effective in preventing opioid addiction in mice. 

Hypocretin, also called orexin, is a peptide that is linked to mood, with hypocretin release in humans being maximal during pleasurable activities and minimal during pain or sadness. The loss of hypocretin neurons is the cause of narcolepsy, which is thought to be an autoimmune disease. People with narcolepsy and mice made narcoleptic have a greatly diminished susceptibility to opiate addiction.  

Researchers have found both humans addicted to heroin and mice addicted to morphine develop higher numbers of hypocretin producing neurons. Morphine causes hypocretin neurons to increase their anatomical connections to pleasure related brain regions. 

The latest study in mice found that administering opioids with suvorexant prevents opioid-induced changes in hypocretin neurons, prevents hypocretin neurons from increasing their connections to the brain’s reward related regions, greatly reduces opioid induced brain inflammation and prevents addictive behavior, such as running in mice expecting to receive their daily morphine dose. Suvorexant given with morphine also greatly reduces morphine withdrawal symptoms, according to the study. 

“The annual US rate of opioid overdose deaths now exceeds 80,000, greater than the annual rates of automobile or gun deaths,” said the study’s senior author, Dr. Jerome Siegel of UCLA Health’s Jane & Terry Semel Institute for Neuroscience and Human Behavior, the UCLA Brain Research Institute and U.S. Department of Veterans Affairs. “Non-opioid analgesics are able to relieve relatively minor pain. But severe burns, cancer, joint inflammation, sickle cell disease, bone damage and many other painful conditions often cannot be effectively treated with non-opioid analgesics.  

“Further studies are needed to determine if the addiction suppressive results seen in mice given suvorexant with morphine are also seen in humans, potentially allowing safer, more effective treatment of pain without the risk of addiction and opioid overdose death,” Siegel continued 

The study included 170 mice that were administered morphine for 14-day periods, 5 postmortem brains of humans with opiate use disorder and 5 control human brains. Trials are necessary to determine whether suvorexant will be as effective in suppressing addiction in humans using opioids for pain relief as it is in mice, Siegel said. 

“The annual US rate of opioid overdose deaths now exceeds 80,000, greater than the annual rates of automobile or gun deaths,” Siegel said. “Non-opioid analgesics are able to relieve relatively minor pain. But severe burns, cancer, joint inflammation, sickle cell disease, bone damage and many other painful conditions often cannot be effectively treated with non-opioid analgesics.  

“Further studies are needed to determine if the addiction suppressive results seen in mice given suvorexant with morphine are also seen in humans, potentially allowing safer, more effective treatment of pain without the risk of addiction and opioid overdose death,” Siegel continued 

Article Citation: McGregor R., Wu M.-F., Thannickal T.C., Li S., and Siegel J.M. (2024). Suvorexant blocks opiate induced anatomical and behavioral changes without diminishing opiate analgesia. Nature Mental Health, 2024. https://doi.org/10.1038/s44220-024-00278-2 

 

Newswise — The ongoing opioid epidemic in the U.S. kills tens of thousands of people every year. Naloxone, sold under the brand name Narcan, has saved countless lives by reversing opioid overdoses. But new and more powerful opioids keep appearing, and first responders are finding it increasingly difficult to revive people who overdose.

Now, researchers have found an approach that could extend naloxone’s lifesaving power, even in the face of ever-more-dangerous opioids. A team of researchers from Washington University School of Medicine in St. Louis, Stanford University and the University of Florida have identified potential drugs that make naloxone more potent and longer lasting, capable of reversing the effects of opioids in mice at low doses without worsening withdrawal symptoms. The study is published July 3 in Nature.

“Naloxone is a lifesaver, but it’s not a miracle drug; it has limitations,” said co-senior author Susruta Majumdar, PhD, a professor of anesthesiology at Washington University. “Many people who overdose on opioids need more than one dose of naloxone before they are out of danger. This study is a proof of concept that we can make naloxone work better — last longer and be more potent — by giving it in combination with a molecule that influences the responses of the opioid receptor.”

Opioids such as oxycodone and fentanyl work by slipping inside a pocket on the opioid receptor, which is found primarily on neurons in the brain. The presence of opioids activates the receptor, setting off a cascade of molecular events that temporarily alters how the brain functions: reducing the perception of pain, inducing a sense of euphoria and slowing down breathing. It is this suppression of breathing that makes opioids so deadly.

The molecular compound described in the paper is a so-called negative allosteric modulator (NAM) of the opioid receptor. Allosteric modulators are a hot area of research in pharmacology, because they offer a way to influence how the body responds to drugs by fine-tuning the activity of drug receptors rather than the drugs themselves. Co-author Vipin Rangari, PhD, a postdoctoral fellow in the Majumdar lab, did the experiments to chemically characterize the compound.

Naloxone is an opioid, but unlike other opioids, its presence in the binding pocket doesn’t activate the receptor. This unique feature gives naloxone the power to reverse overdoses by displacing problematic opioids from the pocket, thereby deactivating the opioid receptor. The problem is that naloxone wears off before other opioids do. For example, naloxone works for about two hours, while fentanyl can stay in the bloodstream for eight hours. Once naloxone falls out of the binding pocket, any fentanyl molecules that are still circulating can re-attach to and re-activate the receptor, causing the overdose symptoms to return.

The research team — led by co-senior authors Majumdar; Brian K. Kobilka, PhD, a professor of molecular and cellular physiology at Stanford University; and Jay P. McLaughlin, PhD, a professor of pharmacodynamics at the University of Florida — set out to find NAMs that strengthen naloxone by helping it stay in the binding pocket longer and suppress the activation of the opioid receptor more effectively.

To do so, they screened a library of 4.5 billion molecules in the lab in search of molecules that bound to the opioid receptor with naloxone already tucked into the receptor’s pocket. Compounds representing several molecular families passed the initial screen, with one of the most promising dubbed compound 368. Further experiments in cells revealed that, in the presence of compound 368, naloxone was 7.6 times more effective at inhibiting the activation of the opioid receptor, partly because naloxone stayed in the binding pocket at least 10 times longer.

“The compound itself doesn’t bind well without naloxone,” said Evan O’Brien, PhD, the lead author on the study and a postdoctoral scholar in Kobilka’s lab at Stanford. “We think naloxone has to bind first, and then compound 368 is able to come in and cap it in place.”

Even better, compound 368 improved naloxone’s ability to counteract opioid overdoses in mice and enabled naloxone to reverse the effects of fentanyl and morphine at 1/10th the usual doses.

However, people who overdose on opioids and are revived with naloxone can experience withdrawal symptoms such as pain, chills, vomiting and irritability. In this study, while the addition of compound 368 boosted naloxone’s potency, it did not worsen the mice’s withdrawal symptoms.

“We have a long way to go, but these results are really exciting,” McLaughlin said. “Opioid withdrawal likely won’t kill you, but they’re so severe that users often resume taking opioids within a day or two to stop the symptoms. The idea that we can rescue patients from overdose with reduced withdrawal might just help a lot of people.”

Compound 368 is just one of several molecules that show potential as NAMs of the opioid receptor. The researchers have filed a patent on the NAMs, and are working on narrowing down and characterizing the most promising candidates. Majumdar estimates that it will be 10 to 15 years before a naloxone-enhancing NAM is brought to market.

“Developing a new drug is a very long process, and in the meantime new synthetic opioids are just going to keep on coming and getting more and more potent, which means more and more deadly,” Majumdar said. “Our hope is that by developing a NAM, we can preserve naloxone’s power to serve as an antidote, no matter what kind of opioids emerge in the future.”

O’Brien ES, Rangari VA, El Daibani A, Eans SO, Hammond HR, White E, Wang H, Shiimura Y, Kumar KK, Jiang Q, Appourchaux K, Huang W, Zhang C, Kennedy BJ, Mathiesen JM, Che T, McLaughlin JP, Majumdar S, Kobilka BK. Negative allosteric modulation of the μ-opioid receptor. Nature. July 3, 2024. DOI: 10.1038/s41586-024-07587-7

Newswise — The U.S. Supreme Court has blocked the Sackler family’s bid for immunity from opioid-related lawsuits in a landmark decision. This ruling marks a pivotal moment in the ongoing opioid crisis, potentially reshaping how litigation against pharmaceutical companies is handled nationwide. It underscores the accountability of the Sacklers for their role in the epidemic and ensures that settlement funds are directed to support affected communities. This decision highlights the importance of justice and reparations for those impacted by opioid addiction.

The Supreme Court’s decision is crucial as it sets a precedent for future opioid litigation and the distribution of settlement funds.

The media is actively covering this significant decision, reflecting the widespread interest and its potential impact. Notable coverage includes:

Newswise Research

Cost may not keep many people from filling opioid addiction treatment prescriptions

Exploitation of supply chain monitoring loopholes fueled US opioid epidemic, study finds

Newswise Experts

Deborah A. Pasko, PharmD, MHA

Cheryl Healton, DrPH, 

Stephen Crystal, PhD

Larissa Mooney, MD

Dr. Ty Schepis, Ph.D., Clinical Psychology

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If you have comments or research to contribute to Newswise, please email us at [email protected].

Newswise — CHAPEL HILL, N.C. – Christian Hendershot, PhD, associate professor of psychiatry and director of the Clinical and Translational Addiction Research Program at the UNC School of Medicine, recently presented early findings from the first completed randomized controlled trial of semaglutide in participants with alcohol use disorder (AUD).

The preliminary and unpublished findings, which were presented at the Research Society on Alcohol’s Annual Meeting, showed a reduction in heavy drinking and drinking quantity among those who were given semaglutide versus the placebo group.

“We believe these findings are promising and warrant further trials of GLP-1 receptor agonists in treatment-seeking participants with alcohol use disorder,” said Hendershot, who is also a member of the Bowles Center for Alcohols Studies at the UNC School of Medicine.

Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) was originally formulated to treat diabetes and has emerged as a weight loss drug. Anecdotal observations from patients have suggested the drug may also reduce alcohol and other substance cravings. This possibility is also consistent with numerous preclinical studies over the past decade, which led Hendershot and other groups to design early randomized clinical trials of GLP-1RAs in participants with AUD.

Participants in the Phase II randomized controlled trial were non-treatment-seeking volunteers who reported symptoms of alcohol use disorder. A total of 48 participants were randomized to medication or placebo groups. Participants assigned to the medication arm received the lower two clinical doses of semaglutide (0.25mg/week, 0.5mg/week) over approximately 2 months. The study was funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA).

Preliminary results from the trial indicate that those taking the medication experienced greater reductions in drinking quantity and heavy drinking more than those in the placebo group. Given the magnitude of the effects at relatively lower doses, it appears that semaglutide could have the potential to reduce drinking to a greater extent than existing medications. With 96% of those in the medication group finishing the study, researchers concluded that the drug was safe and well tolerated in this population.

Replication studies will be needed to further confirm the safety, tolerability, and efficacy of semaglutide at higher doses in this population, and to identify patient subgroups that are more or less responsive to GLP-1RAs.

Other UNC-based co-investigators on the study include Klara Klein, MD, PhD, assistant professor at the Department of Medicine’s Division of Endocrinology and Metabolism; Amanda Tow, MD, PhD, assistant professor in the Department of Psychiatry; and Robyn Jordan, MD, PhD, associate professor in the Department of Psychiatry and medical director of the UNC Addiction Medicine Program.

FOR IMMEDIATE RELEASE:

Newswise — BLOOMINGTON, Ind. — New research from the Indiana University Kelley School of Business explains how pharmaceutical companies were able to saturate the country with massive quantities of opioids, despite efforts by the Drug Enforcement Administration to regulate their supply.

The research identifies a loophole in the DEA’s monitoring system exploited by some pharmaceutical companies, leading to an oversupply of opioid drugs in communities. The hallmark of this activity was high supply chain complexity, such as pharmacies with dozens of distributors across the country.

The same research also documents how the opioid epidemic — commonly regarded as a national public health crisis among white Americans — had a much deeper impact in Black communities, where overdose deaths tripled from 2014 to 2020.

“We believe we are the first to uncover insights into the supply chain mechanisms that were used to evade the DEA and fuel the opioid crisis,” said Jonathan Helm, professor of operations and decision technologies and the W.W. Grainger Inc. Faculty Fellow at the Kelley School. “Up until now, the focus has been on each of the pharmaceutical companies individually, ignoring the huge impact of the broader supply chain.”

“No one was looking at it from a supply chain perspective,” added Iman Attari, a Kelley School doctoral candidate in operations and decision technologies and the paper’s corresponding author.

Attari, Helm and Jorge Mejia, an associate professor in the Kelley School, analyzed information in the 2019 release of the DEA’s Automation of Reports and Consolidated Orders System — commonly known as the ARCOS database — which tracked each shipment in the U.S. opioid supply chain from 2006 to 2014.

Their paper, “Hiding Behind Complexity: Supply Chain, Oversight, Race, and the Opioid Crisis,” appears in the latest issue of the journal Production and Operations Management.

The researchers uncovered how supply chain complexity may have facilitated the influx of large qualities of opioids into the market, undetected by the DEA. Their research combined ARCOS data about pharmacies’ opioid dispensing and supply chain structures with county-level demographics and socioeconomic factors.

Using a fixed effect model, they found that a one-unit increase across three dimensions of supply chain complexity was associated with a 16% increase in opioid dispensing.

DEA monitoring involves using ARCOS to collect data on all shipments of controlled substances, and requiring manufacturers and distributors to report suspicious orders of unusual size and frequency.

“The issue was that pharmacies wanting to have large shipments were very smart about it,” Attari said. “Instead of placing an order for a large shipment from one single distributor, they broke down that large order across multiple distributors. They got smaller shipments from different distributors; when added up, it was a huge order. Each distributor is only going to see the data from the pharmacy that links themselves to it, and not to shipments from other distributors.”

As a result, the DEA monitoring system failed. By using more suppliers, pharmacies were able to evade detection.

Another factor they studied was the location of distributors. Because of the DEA’s structure, with 23 often independently operated field divisions spread across the U.S., the researchers found that a lack of coordination and aggregation of information among them was another factor in overlooking potentially suspicious activity.

“Even if a supplier reports a suspicious order in one division, other divisions that the pharmacy orders from are unlikely to be informed,” they wrote.

“It cannot be just ‘business,’ because when you look at it from a business standpoint, it makes more sense to work with one distributor because you benefit from economy of scale,” Attari said. “It is expected for a pharmacy to have one or two distributors, or at most three distributors of opioid drugs.

“When we saw pharmacies in the data set with 25 distributors — all over the U.S. — that was a strong indication that they were trying to mess with the monitoring system.”

The research found that supply chain complexity had a stronger association with the increase in opioid dispensing in non-white communities. A 10% increase in the non-white proportion of the population yielded a 3.39% increase in the overall dispensing by pharmacies with high supply chain complexity.

“Communities of color have been historically under-resourced and neglected by many government and social services,” the researchers wrote. “In the context of the opioid crisis, it appears that the DEA has spent more effort arresting non-White drug users than on regulating the flow of opioids from pharmaceutical companies into non-White communities.”

To be certain that their analysis was distinguishing between legitimate medical use and non-medical, recreational demand, they compared statistics for the reformulated OxyContin, which was redesigned to prevent abuse.

“In a novel approach, we leverage the fact that different pharmacies received their first shipment of reformulated OxyContin at different times and use a difference-in-differences model to estimate the heterogeneous effect of the shock on dispensing,” they wrote. “As the reformulated OxyContin stifled (non-medical) demand, high-complexity pharmacies experienced a 15.31% greater reduction in dispensing compared to lower-complexity pharmacies, suggesting that their excess dispensing was indeed satisfying non-medical/recreational demand.”

As a follow-up to this paper, the researchers are investigating the dynamics between major chain pharmacies and their distributors, and how they may facilitate the oversupply by pharmacies. Their initial findings suggest that the pharmacies’ practice of self-distribution, where they distribute opioids from their own distribution centers, combined with their close ties to large distributors, also may have led to excessive opioid dispensing without adequate oversight by the DEA.

EMBARGOED: FOR RELEASE 14:00 (2:00 pm) U.S. Eastern Time Friday, 21 June 2024

Chilling discovery: Cold-sensing protein may pave the way for safer pain relief

New ASU study reveals evolution of human cold and menthol sensing protein, offering hope for future non-addictive pain therapies.

Newswise — Chronic pain affects millions worldwide, and current treatments often rely on opioids, which carry risks of addiction and overdose. 

Non-addictive alternatives could revolutionize pain management, and new research targeting the human protein which regulates cold sensations, brings scientists closer to developing pain medications that don’t affect body temperature and don’t carry the risks of addiction. 

Research published in Science Advances on June 21, led by Wade Van Horn, professor in Arizona State University’s School of Molecular Sciences and Biodesign Center for Personalized Diagnostics, has uncovered new insights into the main human cold and menthol sensor TRPM8 (transient receptor potential melastatin 8). Using techniques from many fields like biochemistry and biophysics, their study revealed that it was a chemical sensor before it became a cold temperature sensor.

“If we can start to understand how to decouple the chemical sensing of cold from actual cold sensing, in theory, we could make side-effect-free drugs,” said Van Horn whose research focuses on membrane proteins involved in human health and disease. “By understanding the evolutionary history of TRPM8, we hope to contribute to designing better drugs that offer relief without the dangerous side effects associated with current painkillers.” 

When a person touches a metal desk and it feels cold, the human body activates TRPM8. For cancer patients who are on certain kinds of chemotherapeutics, touching a desk can hurt. TRPM8 is also involved in many other types of pain as well, including chronic neuropathic and inflammatory pain. 

By further understanding this specificity of the chemical sensing of cold versus physically sensing cold, scientists can target relief without triggering the temperature regulation side effects often seen in TRPM8 clinical trials for pain treatments. 

In the research, the team used ancestral sequence reconstruction, a time machine for proteins of sorts, compiling the family tree of TRPM8 that exists today and then used that information to determine what the proteins from long-extinct animals might have looked like. 

Using computational methods to resurrect ancestral primate, mammalian, and vertebrate TRPM8, the researchers were able to understand how TRPM8 has changed over hundreds of millions of years by comparing the sequences of current proteins to predict the sequences of their ancient ancestors. Additionally, the combination of lab experiments and computational studies enable the researchers to identify critical places in TRPM8 that allow a more clear understanding of temperature sensing, which can be tested in subsequent experiments. 

“Comparative dynamics analysis of ancestral and human TRPM8 also supports the experimental data and will allow us to identify critical sites in temperature sensing, which we will be testing soon,” said Banu Ozkan, professor in ASU’s Department of Physics, who was involved in the study.

The team then expressed these ancestral TRPM8s in human cells and characterized them using various cellular and electrophysiology techniques.

“Ancestral protein-based studies allow us to focus on the lineage of most interest, such as human TRPM8, to alleviate concerns arising in drug discovery from speciation differences, like in mice and humans,” said first author on the study Dustin Luu, an ASU School of Molecular Sciences doctoral alumnus, and current postdoctoral fellow in ASU’s Biodesign Center for Personalized Diagnostics.

Luu continued: “We discovered that surprisingly menthol sensing appeared way before cold sensing. The difference in appearance and attenuation of these activation modes suggest they are separate and can be disentangled with further research enabling new pain therapies without the adverse side effect in thermal sensing and thermal regulation, which has plagued TRPM8-targeted clinical trials.”

As science continues to uncover the mysteries of our biological mechanisms, studies like this exemplify how evolutionary biology and modern pharmacology can collaborate to address pressing medical needs and improve the quality of life for those suffering from chronic pain.

Additional researchers involved in the study include Nikhil Ramesh, and I. Can Kazan from Arizona State University’s Department of Physics; Karan Shah from ASU’s School of Molecular Sciences; Gourab Lahiri and Miyeko Mana from ASU’s School of Life Sciences. 

Newswise — In an op-ed published in The New York Times, U.S. Surgeon General Vivek Murthy called on Congress to require a social media warning label. This would be similar to those of tobacco and alcohol products. 

In the op-ed, Murthy mentioned the toll social media is having on the mental health among young people. 

According to Murthy, he would like the warning to include an alert to users about the potential mental health harms of websites and apps. 

George Washington University has experts available who can offer insight and analysis. If you would like to schedule an interview, please contact Katelyn Deckelbaum, [email protected].

Lorenzo Norris, is an associate professor of psychiatry and behavioral sciences and chief wellness officer at the GW School of Medicine and Health Sciences.

Amir Afkhami, an expert in psychiatry, holds a joint appointment at the GW School of Medicine and Health Sciences and the Milken Institute School of Public Health. An expert in psychiatry, much of his current work focuses on psychiatric services and education, behavioral health policy, and the mental health consequences of conflict.

Lorien Abroms is a professor of prevention and community health at the GW Milken Institute School of Public Health. She has studied how social media and digital communication technology can be used for health promotion. She can also talk about the potential for negative impact on teens and young adults.Tony Roberson, an associate professor of nursing at the GW School of Nursing, is a mental health expert. He is an expert on anxiety, depression and childhood development. 

Vikram Bhargava, assistant professor of strategic management & public policy, is an expert on technology addiction and his research centers around the distinctive ethics and policy issues that technology gives rise to in organizational contexts. Bhargava authored a research article in Business Ethics Quarterly, titled  “Ethics of the Attention Economy: The Problem of Social Media Addiction“, which dives into why scholars, policy makers, and the managers of social media companies should treat social media addiction as a serious moral problem. It also contextualizes social media addiction in comparison to other addictive products, like cigarettes or alcohol.

Newswise — WASHINGTON – A rigorous, comprehensive synthesis of evidence from 62 studies related to the use of oral nicotine pouches by Georgetown University’s Lombardi Comprehensive Cancer Center scientists and colleagues provides a much-needed assessment of how these products could lead to potential harmful consequences if used by young people.

Oral nicotine pouches were first introduced in the U.S. in the past decade and are pre-portioned white granular packets containing nicotine placed between the gums and lips, marketed as tobacco-free, and are sold in various flavors and nicotine strengths.

The findings appeared in Nicotine and Tobacco Research on June 17, 2024.

“Oral nicotine pouches are rapidly increasing in popularity. While they may present a less harmful nicotine alternative for cigarette users, there is considerable concern about them becoming a new form of nicotine dependence, especially in youth who don’t use tobacco or nicotine,” says the study’s corresponding author Nargiz Travis, MSPH, Project Director for the Center for the Assessment of Tobacco Regulations (CAsToR) at Georgetown Lombardi. “As with electronic cigarettes, the wide variety of flavors and aggressive marketing campaigns that we are seeing, especially via social media, have the potential to appeal to youth, providing a new pathway to nicotine dependence.”

The investigator’s analysis was based on 45 academic and 17 industry-funded studies, mostly from the U.S. Sales of the products have been concentrated in Scandinavia and the U.S., mainly because of the established smokeless tobacco market in these regions.

In the U.S., the researchers found, based on nationally representative surveys, that through 2023, oral nicotine pouches were currently used by 1.5% of all youth while lifetime use by young people was under 2.5%. In terms of awareness of the products, between 35% to 42% of U.S. adolescents and young adults have heard of oral nicotine pouches and 9% to 21% of tobacco-naïve (non-tobacco users) youth surveyed were not opposed to trying them. U.S. adult usage estimates varied widely across surveys; in 2023, 0.8-3% of Americans currently used the products while 3-16% used them at some point in time. In view of rising nicotine pouch sales trends in 2024, their use in the U.S. population has likely increased.

The investigators’ findings suggest fewer harmful chemical compounds are present in the pouches and occur at lower levels than in cigarettes and smokeless tobacco, with the exception of formaldehyde. However, an analysis of 37 oral nicotine pouches of different brands, nicotine strengths, and flavors yielded a wide range of total nicotine content from 0.89 to 6.73 milligrams per pouch.

“Because oral nicotine pouches do not contain tobacco leaves, they are often marketed as tobacco-free, but we found that descriptor may confuse the understanding of the source of nicotine and may be associated with the perception that they are not as harmful as other tobacco products,” says Travis. “In the U.S., oral nicotine pouches are currently neither authorized by the FDA for marketing as a modified-risk product nor approved as a cessation product. It is important to know that nicotine is an addictive chemical with harmful health effects, regardless of whether it is synthetic, meaning tobacco-free, or derived from tobacco.

One of the studies included in the authors’ analysis was a U.S. survey of young adults 18-34 years of age, many of whom used cigarettes and e-cigarettes. The survey found that among those who had tried nicotine pouches, curiosity about the product (28%), flavors (26%), and the ability to use in places where other tobacco products are prohibited (26%) were among the main reasons for trying the pouches. The availability of flavors (31%) was the main motive for use in another U.S. sample of adult current nicotine pouch users.

Leading brands of the products are currently owned by major tobacco companies. The authors note that a substantial investment in marketing by the companies suggests that oral nicotine pouches are becoming increasingly important to the tobacco industry.

“As more evidence on oral nicotine patches becomes available, and more importantly, more independent studies become published, it will

be essential to conduct further analyses comparing the findings of industry vs. non-industry sponsored research and critically assess the quality and risk of bias of such studies,” concludes Travis.

###

Other authors in addition to Travis include Hayoung Oh, Radhika Ranganathan and David Levy at Georgetown Lombardi Comprehensive Cancer Center. Kenneth Warner is at the University of Michigan; Rafael Meza is at the BC Cancer Research Centre, Vancouver, Canada; Maciej Goniewicz is at Roswell Park Comprehensive Cancer Center, Buffalo, NY; and Jamie Hartmann-Boyce is at the University of Massachusetts Amherst.

This work was supported by National Cancer Institute and Food and Drug Administration grant #U54CA229974.

Goniewicz received a research grant from Pfizer and served as a member of the scientific advisory board to Johnson & Johnson. The other authors declared no conflicts of interest related to the study.

About Georgetown University’s Lombardi Comprehensive Cancer Center

Georgetown’s Lombardi Comprehensive Cancer Center is designated by the National Cancer Institute (NCI) as a comprehensive cancer center. A part of Georgetown University Medical Center, Georgetown Lombardi is the only comprehensive cancer center in the Washington D.C. area. It serves as the research engine for MedStar Health, Georgetown University’s clinical partner. Georgetown Lombardi is also an NCI recognized consortium with John Theurer Cancer Center/Hackensack Meridian Health in Bergen County, New Jersey. The consortium reflects an integrated cancer research enterprise with scientists and physician-researchers from both locations. Georgetown Lombardi seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic, translational and clinical research, patient care, community education and outreach to service communities throughout the Washington region, while its consortium member John Theurer Cancer Center/Hackensack Meridian Health serves communities in northern New Jersey. Georgetown Lombardi is a member of the NCI Community Oncology Research Program (UG1CA239758). Georgetown Lombardi is supported in part by a National Cancer Institute Cancer Center Support Grant (P30CA051008). Connect with Georgetown Lombardi on Facebook (Facebook.com/GeorgetownLombardi) and Twitter (@LombardiCancer).

About Georgetown University Medical Center

Georgetown University Medical Center (GUMC) is an internationally recognized academic health and science center with a four-part mission of research, teaching, service and patient care (through MedStar Health). GUMC’s mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis — or “care of the whole person.” The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health.  Connect with GUMC on Facebook  (Facebook.com/GUMCUpdate) and Twitter (@gumedcenter).

Newswise — Two issues have surged in awareness across America in recent years: the toll of firearm injuries and deaths, and the impact of mental health conditions. 

These two issues intersect in multiple ways – and a growing number of people are directly or indirectly affected by one or both of them. 

That’s why it’s important for you to know some key things about the risk of firearm-related incidents involving people with mental health conditions, and take steps to reduce that risk, say three experts from Michigan Medicine, the University of Michigan’s academic medical center, and the Institute for Firearm Injury Prevention who have training and experience in both fields. 

The group discusses these risks and risk-reduction steps in depth during a recent livestream. 

Below are some key takeaways from that chat with Victor Hong, M.D., director of Psychiatric Emergency Services at U-M Health, child psychologist and firearm injury prevention researcher Cynthia Ewell Foster, Ph.D., and Mark Ilgen, Ph.D., director of U-M Addiction Treatment Services.

1. Suicide is the top concern when it comes to mental health and firearms – but not the only one

More than half of all firearm deaths in the United States are suicides, and firearms are involved in half of all suicide deaths. 

Not all people who die by suicide have a formal mental health diagnosis, so it’s important for everyone to know the warning signs of suicide and what to do if someone they know is showing some or all of these signs. 

There are some warning signs specific to children and teens too.

These signs include worsening or severe depression symptoms, expressing hopelessness or feelings of being a burden, extreme mood swings, an increase in use of drugs and alcohol, taking risks, seeming to be out of touch with reality, as well as speaking, writing or posting on social media about wanting to die, “unalive” themselves, or not live any longer.

2. Easy access to firearms increases risk 

Being able to get access to a loaded handgun or long gun – their own or someone else’s – greatly increases the risk of suicide death for people experiencing a mental health crisis or suicidal thoughts and impulses. 

Why?

“There’s a speed and irreversibility of firearm usage in a suicide attempt that is very unique,” said Hong, who leads a team that offers 24/7/365 care for psychiatric emergencies of all kinds. 

“When somebody is in a mental health crisis and it’s clear that those imminent warning signs of suicide are there, firearms at the very least need to be secured in some fashion.” 

Hong’s team members screen nearly every patient seeking emergency mental health care at U-M Health for firearm access.

If there are firearms in their home, those should be locked with a gun lock or in a gun safe, with ammunition stored elsewhere. 

Many police stations, sheriff’s offices and other locations make gun locks available for free; the Project Childsafe website is one way to find local agencies that provide them.

Even better: temporarily remove firearms from all the places a person in crisis can access, and secure them in another location, whether that’s a gun shop, a law enforcement agency or the home of a trusted person who will keep them locked with ammunition stored separately.   

Firearm owners should also keep their weapons secured if a child or teen might have access to them, to prevent needless tragedy including suicide and accidental or intentional shootings. 

Michigan law now requires this.

“Everybody has a role to play in suicide prevention in this country, and one of the most important things we can all do is to be sure that we’re storing our firearms safely at all times and controlling who has access to them,” said Ewell Foster. 

“If you look at kids in this country who have died by suicide, and you look at where they’re getting those firearms, they are getting them from people who love them. They’re getting them from their house, their parents, their grandparents, their aunts and uncles.”

Ilgen likens suicide risk to a graph with a curve that rises slowly or sharply to a peak – with the top of the curve being the moment where they are at highest risk of harming themselves. 

“If someone enters that upward slope at a time where they have very easy access to something that’s very lethal, that’s when things get very concerning quickly,” he said.

“Even a step that isn’t foolproof but can slow access can buy someone a few minutes or hours before they might act on a suicidal thought. That can make all the difference in helping to keep someone safe and getting someone through that curve” and help them avoid death or injury. 

3. Help is always available for a person in crisis

The 988 Suicide and Crisis Lifeline can be reached by dialing 988 from any phone, by texting 988 from any mobile phone, or using the webchat function at 988lifeline.org. 

It offers live help around the clock, every day of the year and can connect the person in crisis, or a person assisting the person in crisis, to local services, too. 

The 988 service includes specialized options for veterans, members of the LGBTQ+ community, people who speak Spanish and other languages, and people who are Deaf or hard of hearing.

No matter whether someone reaches out to 988 or to a trusted family member, friend, teacher, coach, clergy member or health care provider, it’s important for everyone to know that there are effective treatments available for mental health conditions of all kinds, and that there is hope.

4. Some groups of people have an elevated risk of firearm suicide

Middle-aged and older men account for most of the suicide deaths in Michigan and other states, and most of these deaths are due to firearms. 

Native Americans, and Black youth, as well as young people living in rural areas, also have higher rates of firearm suicide than other groups, says Ewell Foster. 

In order to reach some of those groups with messages about storing firearms safely and seeking help when they need it in a crisis, Ewell Foster and her colleagues have been working to understand which messengers will be most effective for different groups, and how to tailor messages to them.

Ilgen, who is also affiliated with the VA Ann Arbor Healthcare System, notes that veterans are also at higher risk of firearm suicide. 

In fact, 70% of all veteran suicide deaths are firearm-related. 

The VA has created multiple programs to try to prevent these tragedies among veterans who receive care from VA clinics and hospitals. 

5. Drug and alcohol problems raise firearm injury and death risk

While many people may think of depression, bipolar disorder and post traumatic stress disorder as the mental health conditions most closely linked to a risk of firearm suicide, Ilgen notes that an increasing amount of evidence points to high risk among people who have substance use issues and use drugs or alcohol heavily. 

“Substance use disorders are impairing – making your judgment a little cloudy – and they’re stigmatized, and that can make someone more likely to be suicidal,” he said. 

“If they’re progressing rapidly from not thinking at all about suicide to engaging in a suicidal behavior, that that’s more likely to occur if they’re using substances and more risky if they have access to a particularly lethal means like a firearm.”

He also worries that one of the approaches used in some addiction treatment programs – having the patient’s loved ones tell them in a formal session what the patient’s addiction has done to harm those around them – may be counterproductive or even dangerous. 

Doing this could increase the chance the patient feels like a burden to others, and turns toward suicide.

6. Risk factors for suicide and firearm violence toward others can be similar 

When you hear about a violent event on the news that involves firearms used against other people, you might assume that the shooter has a mental illness. 

But Hong notes that it’s important to know that people with serious mental illnesses are more likely to be victims of firearm violence than perpetrators. 

That said, some of the same risk factors and warning signs that someone may be at high risk of turning a firearm on themselves also could signal a risk that they will use a firearm against someone else. 

That’s why Hong and his psychiatric emergency team screen for those risk factors, as well as firearm access, when a patient comes to them in crisis. 

Murder-suicides, in which a person kills a loved one immediately before killing themselves, often happen because someone has decided they don’t want to continue living and that they want to take loved ones or others with them, Hong says. 

7. “Red Flag” laws can help reduce risk in extreme situations 

What can someone do if they’re very concerned that a loved one, friend or co-worker who owns firearms could be at high risk of hurting themselves or others, but that person does not see the risk or want to secure their firearms voluntarily?

In a growing number of states, including Michigan, public safety and court officials can be asked to determine next steps under an Extreme Risk Protection Order law, also known as ERPO or “red flag” law. 

Michigan’s ERPO law went into effect in February 2024. 

The U-M Institute for Firearm Injury Prevention has a free online toolkit that explains the law and how individuals can use it to petition a judge to authorize law enforcement to remove firearms from a person’s possession in an orderly way. 

It’s located at firearminjury.umich.edu/erpo-toolkit.

“This is an evidence-based policy intervention that can prevent a host of adverse outcomes with firearms,” saidEwell Foster, who has spent time with family members of those who have suffered a tragic loss of a loved one from a firearm injury that could have been prevented. 

Prior to Michigan’s ERPO law, she said, “I’ve had moms of young adult males who have a high risk of suicide say, ‘I’m so worried, I’ve asked him to get rid of his firearm and I feel like there’s nothing I can do.’ When people are at risk their loved ones are worried about them and ERPO is another tool in our toolkit to try to support someone who’s at risk.” 

She notes that U-M researcher April Zeoli, Ph.D., policy core director at the institute and associate professor in of the School of Public Health, is one of the nation’s top experts on studying what happens in states that enact ERPO laws, and helped inform the policy process that led to Michigan’s law. 

“It’s really important for folks to know that there are legal checks and balances as part of this law, and that it’s not like someone is going to show up at a person’s house and take away their firearms,” immediately after someone files an ERPO petition, she explains. 

Hong added, “This is not an effort to remove firearms from law-abiding citizens who are low-risk, minding their own business. 

This is really for people for whom there are numerous red flags and risk factors of potential harm to self and others.” 

He also notes that removal of firearms by law enforcement only takes place after a judge rules based on the evidence, and that the removal is temporary.

8. Everyone can make a difference

Ewell Foster likens this moment, when awareness of firearm injury and mental health are both rising, to a time decades ago when there was rising awareness and action around drunk driving. 

“Our society has gotten comfortable saying to one another, ‘Hey, I think you’ve had too much to drink, I’m going to take your car keys and how about I run you home,’ and that’s a socially acceptable thing to do now in this country,” she said. 

“I think we need to work on getting there around mental health and normalizing saying things like, ‘I really care about you, I’ve noticed these changes in you, I’m even wondering if you’re thinking about suicide. How can I help you?’”

“So much of what we’ve learned about how to protect people is about these caring behaviors, and actively working to be sure they feel like they have belonging and connectedness,” she said. 

“I want people to feel empowered that they can reach out and ask, and they can make sure their firearms are stored safely.”