Category: From Newswise – Substance Abuse

The FDA announced the nasal spray based form of Narcan – which reverses opioid overdoses and previously required a prescription – can now be sold over the counter.

John Cawley, health economist at Cornell University, is co-director of the Institute on Health Economics, Health Behaviors and Disparities. He says this is an important step, but there will still be a financial cost. 

Cawley says:

“Naloxone is, from the perspective of a layperson, a miracle drug that can bring back, from the brink of death, people who’ve overdosed on opiates such as heroin. Allowing it to be sold without a prescription is a critically important step. There are few risks – no one can get high from it and the benefits are potentially enormous.

“Allowing naloxone to be sold over-the-counter (without a prescription) may considerably increase its use. It significantly decreases the time cost of acquiring it. People can soon just buy it at a convenience store, or even order it online for home shipment. 

“While making sales over the counter reduces time cost, there is still a financial cost. As always, pharmaceutical prices are a contentious issue involving important tradeoffs. Pharma companies want to earn profits, and as a society we want there to be financial incentives for them to develop new life-saving drugs and ways of delivering them. But we also want those innovations to benefit as many people as possible.

“Emergent BioSolutions hasn’t yet announced what the over the counter version will cost; hopefully it will be low enough to facilitate widespread adoption. However, the government and nonprofits could also consider subsidies to encourage people to purchase and keep naloxone in various locations and on their persons.

“One contrast is the EpiPen: these autoinjectors of epinephrine can save the lives of people who have a severe allergic reaction (anaphylaxis). These remain prescription, however (not OTC), and the brand-name version costs hundreds of dollars, and states are considering laws to limit their price.”

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BYLINE: Enrique Rivero

EMBARGOED FOR USE UNTIL

11 A.M. (ET) on MAR. 29, 2023

Newswise — Overdose mortality among people age 65 and older quadrupled over 20 years, suggesting the need for greater mental health and substance use disorder policies addressed at curbing the trend, a new research paper finds.

The deaths stemmed from both suicides and accidental overdoses, with nearly three-fourths of the unintended fatalities involving illicit drugs such as synthetic opioids like fentanyl, heroin, cocaine, and methamphetamines.  Prescription opioids, antidepressants, benzodiazepines, antiepileptics and sedatives were used in 67% of intentional overdoses.

“The dramatic rise in overdose fatalities among adults over 65 years of age in the past two decades underscores how important it is for clinicians and policymakers to think of overdose as a problem across the lifespan,” said co-author Chelsea Shover, assistant professor of medicine in the division of general internal medicine and health services research at the David Geffen School of Medicine at UCLA. “Updating Medicare to cover evidence-based treatment for substance use disorders is crucial, as is providing harm reduction supplies such as naloxone to older adults.”

The paper will be published March 29 in JAMA Psychiatry.

The researchers used the U.S. Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (WONDER) database to calculate annual overdose deaths among seniors from 2002 to 2021, comparing demographics, specific drugs, and whether the deaths were intentional, unintentional, or undetermined.

Overall, they found that fatal overdoses quadrupled from 1060 in 2002 (3 per 100,000 population) to 6,702 (12 per 100,000) in 2021.  The highest rates were among Blacks, at 30.9 per 100,000.

Among the other findings:

• By 2021, 1 in 370 senior deaths stemmed from overdoses, with 3814 of those (57%) involving opioids, 2587 (39%) from stimulants, and 1204 (18%) a combination of both
• About 13% (882) of overdoses in 2021 were intentional, 83% (5,541) were unintentional, and 4% (274) were undetermined, and 5 (0.07%) were homicide
• Females accounted for 505 489 of 882 (57%) of intentional overdoses and 1594 of 5541 (29%) of accidental overdoses
• Intentionality differed by race and ethnicity: 31 of 83, or 37%, of overdoses among Asians were intentional, compared to, 805 of 4848 (17%) among whites, and 15 of  1665 (1%) among Blacks
• Alcohol poisoning deaths rose from 10 (less than 0.03per 100,000) to 281 (0.5 per 100,000)

“Even though drug overdose remains an uncommon cause of death among older adults in the U.S., the quadrupling of fatal overdoses among older adults should be considered in evolving policies focused on the overdose epidemic,” the researchers write. “Current proposals to improved mental health and substance use disorder coverage within Medicare, for example, applying mental health parity rules within Medicare, acquire greater urgency in light of this study’s results.”

Keith Humphreys of Stanford University and Veterans Affairs Palo Alto Health Care System was the study’s co-author.

Article: JAMA Psychiatry. doi:10.1001/jamapsychiatry.2023.0310 Published online March 29, 2023

Newswise — CHICAGO – The American Society of Anesthesiologists (ASA) urges the public to help fight the opioid epidemic by learning to recognize and respond to an overdose. This includes understanding how to use naloxone, a life-saving medication approved today for sale over the counter by the U.S. Food and Drug Administration.

“While naloxone doesn’t treat the underlying epidemic, it can prevent the most tragic consequences. Expanding its availability throughout our communities will help ensure equitable access to this vital treatment,” said ASA President Michael W. Champeau, M.D., FAAP, FASA. “It’s important to understand that overdoses don’t only impact those with a prescription for opioids or those who live with someone with substance use disorder. Anyone can encounter a person experiencing an overdose at any time, anywhere – in restrooms, parking garages, on public transportation. And anyone could save a life by knowing how to administer CPR and naloxone.”

Naloxone – commonly sold as a nasal spray – is safe, easy to use and quickly reverses an opioid overdose by blocking the effects of the drug, restoring breathing and consciousness. It was previously available with or without a prescription, but sold behind the pharmacy counter. With the significant stigma associated with opioid use, many people may be afraid to ask the pharmacist for it.

“No one should have to suffer the loss of a loved one to overdose nor the deeply unsettling experience of having to revive someone they know. Yet this epidemic makes it likely we will encounter someone experiencing an overdose at some point,” said Bonnie Milas, M.D., clinical professor of anesthesiology and critical care medicine at the University of Pennsylvania in Philadelphia and a member of the ASA Committee on Trauma and Emergency Preparedness. Dr. Milas lost both of her sons to accidental overdoses. “While I have no remaining children, naloxone gave me more time with my sons and gave my sons more opportunities to find success. You never know when one more chance will turn into lifelong healing, which is why I am deeply committed to reducing the stigma associated with opioid use disorder and saving lives from opioid overdoses.”

Dr. Milas notes physician anesthesiologists are pain medicine experts who have a specialized understanding of opioids and their potentially life-threatening effects. ASA and its members are uniquely qualified to play a leading role in this critical public health issue.

The Society encourages the public to take the first step to becoming immediate responders by knowing the common signs of an overdose, including:

• Shallow, slow or irregular breathing (fewer than eight breaths a minute or a gap of more than 10 seconds between breaths)
• Small pupils
• Extreme sleepiness or unconsciousness (e.g., “passed out”)
• Inability to talk
• Blue or gray skin color, with dark lips and fingernails
• Snoring or gurgling sounds
• Confusion
• Vomiting
• Seizures

ASA also recommends the creation of a voucher system – supported by settlement funds provided by opioid manufacturers and distributors – for patients to receive access to the life-saving medication, as well as a nationwide education and training program on its safe use. A mail-to-home option for naloxone – similar to the U.S. government’s free COVID-19 test mailing program – could provide even wider access.

To learn more about naloxone, as well as how to recognize an opioid overdose, react and revive, visit www.REVIVEme.com.

THE AMERICAN SOCIETY OF ANESTHESIOLOGISTS

Founded in 1905, the American Society of Anesthesiologists (ASA) is an educational, research and scientific society with more than 56,000 members organized to raise and maintain the standards of the medical practice of anesthesiology. ASA is committed to ensuring physician anesthesiologists evaluate and supervise the medical care of patients before, during and after surgery to provide the highest quality and safest care every patient deserves.

For more information on the field of anesthesiology, visit the American Society of Anesthesiologists online at asahq.org. To learn more about the role physician anesthesiologists play in ensuring patient safety, visit asahq.org/MadeforThisMoment. Like ASA on Facebook, follow ASALifeline on Twitter.

 

Newswise — Recordings of media briefings will be posted by 10 a.m. Eastern Time on each day. Watch recorded media briefings at: www.acs.org/ACSSpring2023briefings.

Note to journalists: Please report that this research is being presented at a meeting of the American Chemical Society.

Monday, Mar. 27, posting by 10 a.m. Eastern Time

What do the elements sound like? (video)
EMBARGOED FOR RELEASE: Sunday, Mar. 26, 2023, 5 a.m. Eastern Time

In chemistry, we have He, Fe and Ca — but what about do, re and mi? Hauntingly beautiful melodies aren’t the first things that come to mind when looking at the periodic table of the elements. However, using a technique called data sonification, a recent college graduate has converted the visible light given off by the elements into audio, creating unique, complex sounds for each one. Today, the researcher reports the first step toward an interactive, musical periodic table. A video on the research is available at www.acs.org/elementmusic. 

W. Walker Smith
Indiana University

Colorful films could help buildings, cars keep their cool
EMBARGOED FOR RELEASE: Sunday, Mar. 26, 2023, 5 a.m. Eastern Time

The cold blast of an air conditioner can be a welcome relief as temperatures soar, but “A/C” units require large amounts of energy and can leak potent greenhouse gases. Today, scientists report an eco-friendly alternative — a plant-based film that gets cooler when exposed to sunlight and comes in a variety of textures and bright, iridescent colors. The material could someday keep buildings, cars and other structures cool without requiring external power.

Sylvia Vignolini, Ph.D.
University of Cambridge

Qingchen Shen, Ph.D.
University of Cambridge

Two meteorites are providing a detailed look into outer space
EMBARGOED FOR RELEASE: Sunday, Mar. 26, 2023, 5 a.m. Eastern Time

If you’ve ever seen a shooting star, you might have actually seen a meteor on its way to Earth. Those that land here are called meteorites and can be used to peek back in time, into the far corners of outer space or at the earliest building blocks of life. Today, scientists report some of the most detailed analyses yet of the organic material of two meteorites. They’ve identified tens of thousands of molecular “puzzle pieces,” including a larger amount of oxygen atoms than they had expected.

Alan Marshall, Ph.D.
Florida State University
National High Magnetic Field Laboratory

Joseph Frye-Jones
Florida State University
National High Magnetic Field Laboratory

New ways to measure curls and kinks could make it easier to care for natural hair
EMBARGOED FOR RELEASE: Sunday, Mar. 26, 2023, 5 a.m. Eastern Time

Black women and others with curly or kinky hair encounter a vast and confusing array of haircare options. Advice on the best products to use for a certain type of hair is often contradictory, and the results can be highly variable. Now, scientists are bringing order to this chaos by identifying properties such as the number of curls or coils in a given length of hair that could eventually help users pick the perfect product and achieve consistent results.

Michelle Gaines, Ph.D.
Spelman College

A puff of air could deliver your next vaccine (video)
EMBARGOED FOR RELEASE: Monday, Mar. 27, 2023, 5 a.m. Eastern Time

Nobody likes needles, but they’re necessary for delivering many vaccines and biologics into the body. But what if those could be puffed through the skin instead, with just a little pressure, like being hit in the arm with a foam toy? Today, scientists report steps toward making that a reality. Using powdered vaccines that don’t require refrigeration and a system driven by compressed gas, their “MOF-Jet” could easily deliver therapeutics against cancer and other diseases in a relatively painless way. A video on the research is available at www.acs.org/mofjet.

Jeremiah Gassensmith, Ph.D.
The University of Texas at Dallas

Yalini Wijesundara
The University of Texas at Dallas

Human cells help researchers understand squid camouflage
EMBARGOED FOR RELEASE: Monday, Mar. 27, 2023, 5 a.m. Eastern Time

Squids and octopuses are masters of camouflage, blending into their environment to evade predators or surprise prey. Some aspects of how these cephalopods become reversibly transparent are still “unclear,” largely because researchers can’t culture cephalopod skin cells in the lab. Today, however, researchers report that they have replicated the tunable transparency of some squid skin cells in mammalian cells, which can be cultured. The work could not only shed light on basic squid biology, but also lead to better ways to image many cell types.

Alon Gorodetsky, Ph.D.
University of California, Irvine

Tuesday, Mar. 28, posting by 10 a.m. Eastern Time

Modern origami method creates glass shapes by folding
EMBARGOED FOR RELEASE: Tuesday, Mar. 28, 2023, 5 a.m. Eastern Time

The ancient art of origami is well known for transforming sheets of paper and other foldable materials into complex 3D shapes. But now, chemical engineers have extended the centuries-old practice to produce intricate shapes made of glass or other hard materials. Their thoroughly modern method, which can be combined with 3D printing, could have applications ranging from sculpture to catalysis and beyond.

Tao Xie, Ph.D.
Zhejiang University

Marijuana-derived compounds could reverse opioid overdoses
EMBARGOED FOR RELEASE: Tuesday, Mar. 28, 2023, 5 a.m. Eastern

There’s been a recent push in the U.S. to make naloxone — a fast-acting opioid antidote — available without a prescription. This medication has saved lives, but it’s less effective against powerful synthetic opioids, such as fentanyl. In an interesting twist, researchers are now looking to cannabidiol (CBD), a component of marijuana, as a possible alternative to the popular antidote. Today, a team reports compounds based on CBD that reduce fentanyl binding and boost the effects of naloxone.

Michael VanNieuwenhze, Ph.D.
Indiana University

Alex Straiker, Ph.D.
Indiana University

Pulsing ultrasound waves could someday remove microplastics from waterways
EMBARGOED FOR RELEASE: Tuesday, Mar. 28, 2023, 5 a.m. Eastern Time

Colorful particles of plastic drift along under the surface of most waterways, from headwater streams to the Arctic Ocean. These barely visible microplastics — less than 5 mm wide — are potentially harmful to aquatic animals and plants, as well as humans. So, researchers are devising ways to remove them and to stop them at their source. Today, a team reports a two-stage device made with steel tubes and pulsing sound waves that removes most of the plastic particles from real water samples.

Menake Piyasena, Ph.D.
New Mexico Institute of Mining and Technology

Wednesday, Mar. 29, posting by 10 a.m. Eastern Time

Fermented coffee’s fruity aromas demystified
EMBARGOED FOR RELEASE: Wednesday, Mar. 29, 2023, 5 a.m. Eastern Time

Specialty coffees are gaining traction in coffeehouses around the world — and now a fermented version could bring a fruity taste to your morning cup of joe. This new kind of beverage has a raspberry-like taste and aroma, but what causes these sensations has been a mystery. Today, scientists report six compounds that contribute to the fermented coffee experience. The work could help increase production of the drink and make it more readily available for everyone to enjoy.

Samo Smrke, Ph.D.
Zurich University of Applied Sciences

Chahan Yeretzian, Ph.D.
Zurich University of Applied Sciences

Obesity treatment could offer dramatic weight loss without surgery or nausea
EMBARGOED FOR RELEASE: Wednesday, Mar. 29, 2023, 5 a.m. Eastern Time

Imagine getting the benefits of gastric bypass surgery without going under the knife — a new class of compounds could do just that. In lab animals, these potential treatments reduce weight dramatically and lower blood glucose. The injectable compounds also avoid the side effects of nausea and vomiting that are common with current weight-loss and diabetes drugs. Now, scientists report that the new treatment not only reduces eating but also boosts calorie burn.

Robert Doyle, Ph.D.
Syracuse University

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BYLINE: Eileen Scahill

Newswise — COLUMBUS, Ohio – There is new evidence that fibromyalgia, and the chronic pain associated with it, could worsen opioid use disorder. Researchers at The Ohio State University Wexner Medical Center, College of Medicine and University of Michigan report their findings in PAIN, the official journal of the International Association for the Study of Pain.

Scientists have long suspected a connection between opioid use disorder (OUD) and chronic pain. Many people first use opioids to treat pain. Chronic pain has been tied to worsening of OUD and even relapse among those in recovery from opioid addiction. However, researchers didn’t know if all pain has the same effect on OUD, or if certain pain diagnoses might have a much larger impact. Different impacts might lead to more targeted treatments for people with pain and OUD.

Symptoms of fibromyalgia include widespread body pain, extreme tiredness and difficulty thinking and sleeping. This condition is thought to involve unusually strong pain signals in the brain.

“Many of the brain pathways and chemicals believed to be involved in fibromyalgia are also involved in opioid addiction. This overlap made us suspect fibromyalgia might worsen OUD. It’s sort of a double hit hypothesis,” said Dr. O. Trent Hall, lead author and an addiction medicine physician in Ohio State’s Department of Psychiatry and Behavioral Health.

The research team surveyed 125 people living with pain and OUD, 39 (31%) of whom met criteria for fibromyalgia. Although all participants had pain and OUD, those with fibromyalgia were much more likely to say pain had worsened their addiction.

Specifically, those with fibromyalgia more often agreed that pain caused them to continue and increase their opioid use, and that they put off seeking help out of fear their pain would be unbearable if they stopped using opioids.

“These are serious findings. Worries about pain may cause people with fibromyalgia and OUD to delay getting addiction treatment. In our current overdose crisis, every day a person puts off OUD treatment might be the last day of their life,” said Dr. Julie Teater, study co-author and medical director of addiction medicine at Ohio State Wexner Medical Center.

Researchers also found fibromyalgia was associated with greater odds of fearing that pain might cause relapse in the future.

“There are ways we can help people living with fibromyalgia. It’s possible that combining lessons learned from years of studying fibromyalgia might one day inform new treatments for chronic pain and OUD. More research is needed. This is just the beginning,” said senior author Dr. Daniel J. Clauw, director of the Chronic Pain and Fatigue Research Center at the University of Michigan.

Craig Bryan and Dr. K. Luan Phan from Ohio State were also involved in this research.

The Care Innovation and Community Improvement Plan, a program of the Ohio Department of Medicaid, provided funding.

Hall gave expert opinion about the opioid crisis to Lumanity and Emergent BioSolutions. Clauw has testified in state lawsuits against opioid manufacturers for their role in the opioid overdose crisis. The remaining authors report no relevant conflicts of interest.

# # #

BYLINE: Greg Bruno

Newswise — Rates of prescriptions for naloxone to people at high risk for opioid overdose, as well as co-prescribing with opioids, has increased in emergency departments throughout the United States over the past decade, providing insight on the positive impact of federal policies and regulations, according to a Rutgers study. 

Federal opioid prescribing guidelines in 2016 made it easier for doctors to prescribe naloxone to patients at high risk for opioid overdose. When used properly, naloxone is highly effective at reversing or reducing the life-threatening adverse effects of opioids and in preventing unintentional death.

But the rise in naloxone prescriptions coincided with an increase in opioid prescriptions during emergency department (ED) stays and at discharge, researchers noted in the study, published in The American Journal of Emergency Medicine.

“It’s good to know that naloxone is being prescribed alongside opioids with increasing frequency,” said Christine Ramdin, an Instructor in the Department of Emergency Medicine at Rutgers New Jersey Medical School, and lead author of the study. “However, these prescribing rates are insufficient to account for the larger rate of patients that come to the ED with an overdose or opioid related complication. This is a trend we need to continuously improve.”

To evaluate changes in naloxone prescribing and co-prescribing with opioids in emergency departments in the U.S., Ramdin and colleagues at Georgetown University analyzed data from the National Hospital Ambulatory Medical Care Survey (NHAMCS), a nationwide representative sample conducted annually by the National Center for Health Statistics.

Of the more than 1.1 billion emergency visits recorded, an estimated 250,365 visits ended with naloxone prescribed at discharge – and the rate of naloxone prescriptions written increased over the years of the study.

There also was an increase in the rate where naloxone was prescribed at discharge when opioids were administered therapeutically during the ED visit. Although the reasons for this are unclear, it may indicate an increase in provider cognizance about the risks of opioids. At the beginning of the study period in 2012, zero visits met this criterion. At the end of the study in 2019, 22,070 visits met the criterion.

Finally, the researchers counted 44,625 visits in which opioids and naloxone were given together at discharge. No co-prescriptions were written in 2012; this climbed to 28,621 in 2019.

Although NHAMCS doesn’t monitor reasons for opioid utilization or prescribing, it does record patient intake data. The researchers found that 62 percent of patients who were prescribed naloxone at ED discharge had a substance-use disorder indicated in the record, Ramdin said.

When asked about reasons for opioid utilization during an ED visit for this population of patients, Ramdin stated, “If someone with opioid use disorder is coming in with an opioid-related complaint, they may be in withdrawal and receive an opioid for this reason in the emergency department. They could have also had a pain complaint.”

Study data was collected before the COVID-19 pandemic and additional research is needed to determine how the pandemic affected these trends, Ramdin said. While it’s likely that prescriptions continued to climb, the opposite could also be true, she said.

“The beginning of the pandemic was chaotic in emergency departments across the country, and that impacted patient care,” said Ramdin. “It’s conceivable that because of the patient load and the types of patients that providers were seeing in the ED that people with opioid-related concerns were not being prescribed naloxone at discharge. However, future research would need to be done to confirm this.”

Newswise — Cannabis use disorder is defined by the Diagnostic and Statistical Manual of Mental Disorders as a problematic pattern leading to clinically significant impairment or distress, with symptoms that may include increased tolerance, withdrawal symptoms, strong desire to use marijuana and spending large amounts of time using cannabis.

Tammy Chung, director of the Center for Population Behavioral Health at Rutgers Institute for Health, Health Care Policy and Aging Research, along with colleagues Marc Steinberg of Rutgers Robert Wood Johnson Medical School and Mary Barna Bridgeman of the Ernest Mario School of Pharmacy, published a commentary in JAMA Psychiatry calling for an important clarification of the way cannabis use disorder is diagnosed, specifically for people who use cannabis for therapeutic purposes. Chung explains why.

What are the challenges to accurately diagnosing cannabis use disorder?

Tammy Chung: One of the challenges involves the rapid increase in state-level legalization of cannabis for therapeutic purposes – also known as medical marijuana.

Specifically, the manual used to define substance-use disorders was developed before the sharp rise in cannabis use for therapeutic purposes. This means that the diagnostic manual considers cannabis to be an illicit substance, even if a person reports cannabis use only for therapeutic purposes, and uses cannabis purchased from a dispensary under appropriate medical supervision, with a valid medical cannabis card.

We suggest the diagnostic manual take into account, as separate from recreational cannabis use, the use of cannabis for therapeutic purposes, given its increasing prevalence. This important distinction is made to avoid misdiagnosis, particularly for individuals who only use cannabis for therapeutic purposes under appropriate medical supervision. This suggested modification to diagnosing cannabis use disorder is similar to the way in which other substances – such as opioids and sedatives, both prescribed and also considered illicit substances – are already treated in the diagnostic manual. 

Since cannabis for therapeutic purposes is only recommended, not prescribed, this raises other challenges, such as the absence of a standard dose due to different ways of consuming cannabis (vaping, edible), the lack of dosing guidelines for specific health conditions, the need for greater regulation of cannabis products, and limited or mixed evidence regarding the therapeutic effects of cannabis for many health conditions.

What do you see as the issue with the current version of this diagnosis protocol?

Chung: The manual’s diagnosis of cannabis use disorder requires an individual to meet only two or more of 11 criteria. These criteria might include only increased tolerance for cannabis and withdrawal symptoms, which are commonly reported by individuals who use cannabis for therapeutic reasons.

People who report these two criteria would technically meet criteria for a cannabis use disorder diagnosis, however these two symptoms alone may not represent problematic use.

 

Explain the changes you propose to the diagnosis.

Chung: In our proposed model, tolerance to cannabis effects and withdrawal symptoms cannot be the only two criteria used to determine if an individual shows impairment in daily activities when taking cannabis for therapeutic purposes. If two or more other symptoms are reported, such as difficulties cutting down on cannabis use or use in hazardous situations (driving while feeling the effects of cannabis), the standard model of diagnosing an individual with cannabis use disorder can still be used.

Our suggested model is based on the one used to diagnose substance use disorder in an individual who has been prescribed medication, such as opioids or sedatives. When taking a prescribed medication, such as a sedative, or a recommended therapeutic, such as cannabis under appropriate medical supervision, symptoms of tolerance and withdrawal may occur as a result of a daily-dosing regimen. Notably, the manual uses different guidelines for diagnosing substance use disorder for a prescription medication and for an illicit substance. We suggest a similar approach could be used to avoid misdiagnosis among individuals who use cannabis only or mainly for therapeutic purposes under appropriate medical supervision.

 

Why is it important to clarify how cannabis use disorder is diagnosed?

Chung: There are limitations to the criteria used to diagnose cannabis use disorder when applied to people who use cannabis for therapeutic purposes. Specific training in assessing the criteria in the context of an individual who uses cannabis for therapeutic purposes could improve the validity of cannabis use disorder diagnoses.

Our model addresses the critical need to improve how cannabis use disorder is diagnosed in individuals who use cannabis for therapeutic purposes. Misdiagnosis, particularly overdiagnosis, represents a medical error with stigmatizing consequences for an individual. Critically, this error could result in flawed understanding of the effects of therapeutic use of cannabis on health because there is potential for misdiagnosis when using the standard diagnostic model for patients who use cannabis only or mainly for therapeutic purposes. 

Newswise — Countries must intensify efforts to track HIV and hepatitis C virus (HCV) incidence among people who inject drugs, and to prioritise this group in prevention and elimination work, according to new University of Bristol-led research, published online in The Lancet Gastroenterology & Hepatology.

UNAIDS and WHO have recommended targets for ending the HIV/AIDS epidemic and eliminating HCV as a public health threat by 2030. To validate these targets, countries must measure HIV and HCV incidence and document a decline over time. People who inject drugs are one of the key risk groups for HIV and HCV infection, so it is important for countries to track HIV and HCV incidence in this high-risk group.

Bristol Medical School researchers sought to address this by summarising global HIV and primary HCV incidence data among people who inject drugs together with age- and sex- or gender-specific incidence data.  They conducted a systematic review and meta-analysis by searching for relevant studies published between 2000 and 2022.  

Data on HIV and HCV incidence in people who inject drugs was limited. Globally, only 14% and 12% of countries have at least one estimate on these measures, respectively.  In many cases, estimates are not recent, not nationally representative, and were usually constrained to a city within a country.  

The availability of estimates was also geographically skewed, with few estimates from middle-income countries for HCV, and only one HIV and HCV incidence estimate from low-income countries. 

Although limited, available data suggest that HIV and HCV incidence are high in this population – on average 1.7 per 100 person per year for HIV and 12.1 per 100 person per year for HCV. These figures mean that, on average, if 100 people who inject drugs uninfected with HIV and HCV were followed for one year, nearly 2 would acquire HIV and 12 would acquire HCV.  However, there is considerable variability in these estimates: the ranges are 0.1-31.8 per 100 person per year for HIV and 0.2-72.5 per 100 person per year for HCV.

Additionally, young people who inject drugs were found to have on average a 1.5-times greater risk of HIV and HCV than older people who inject drugs, and women had a 1.4-times greater risk of HIV and a 1.2-times greater risk of HCV than men.

The findings suggest there is a pressing need for most countries to scale-up measurement and monitoring of HIV and HCV incidence among people who inject drugs, and to prioritise this population in prevention and elimination efforts.  In addition, given that young people who inject drugs and women who inject drugs have higher risk of getting infected with both HIV and HCV, age-appropriate and gender-appropriate prevention measures are urgently needed to reach and engage with these vulnerable risk subgroups.

Dr Adelina Artenie, Senior Research Associate in Mathematical Epidemiology in Bristol Medical School: Population Health Sciences (PHS) and corresponding author of the paper, said: “It can be challenging and expensive to measure HIV and HCV incidence, which is probably why so few estimates are available.

“Given how incomplete the data on HIV and HCV incidence are among people who inject drugs, the true scale of these epidemics globally remains unknown. If there are no data to understand the scale of transmission in a country, we cannot expect timely action to reduce it. This means that people who inject drugs could be overlooked when prevention and treatment strategies are put in place to eliminate HIV and HCV in a country.

“We hope that our systematic review draws attention to the importance of monitoring the HIV and HCV epidemics among people who inject drugs and to the need to prioritise them for prevention and care.”

Peter Vickerman, Professor of Infectious Disease Modelling from the Bristol Medical School: PHS and NIHR Health Protection Research Unit (NIHR HPRU), the paper’s senior author, explained: “There is a global move to eliminate HIV and HCV but either we have no data on the risk of infection among people who injects drugs, or the risk is generally high.

“To be able to reach elimination, we need to improve interventions for this vulnerable group and collect data to show that we have achieving progress. Both of these things need to be improved.

“One option is to use routine collected programmatic data that includes repeat HIV and/or HCV testing. This data is collected in many programmes for people who inject drugs, but is rarely analysed to estimate incidence rates and trends over time.”

A previous study done by the research team has shown the utility of this type of data for documenting decreases in HIV incidence in challenging settings. These results are promising because this data is available in many settings but under-utilised, suggesting a way forward for improving the evidence base for how we are progressing towards elimination.

The study was funded by the Canadian Institutes of Health Research, Fonds de recherche du Québec–Santé, Canadian Network on Hepatitis C, National Institute for Health and Care Research, and WHO.

Paper

‘Incidence of HIV and hepatitis C virus among people who inject drugs, and associations with age and sex or gender: a global systematic review and meta-analysis’ by Adelina Artenie, Peter Vickerman et al. in The Lancet Gastroenterology & Hepatology [open access]

Newswise — INDIANAPOLIS, March 28, 2023 — There’s been a recent push in the U.S. to make naloxone — a fast-acting opioid antidote — available without a prescription. This medication has saved lives, but it’s less effective against powerful synthetic opioids, such as fentanyl. In an interesting twist, researchers are now looking to cannabidiol (CBD), a component of marijuana, as a possible alternative to the popular antidote. Today, a team reports compounds based on CBD that reduce fentanyl binding and boost the effects of naloxone.

The researchers will present their results at the spring meeting of the American Chemical Society (ACS). ACS Spring 2023 is a hybrid meeting being held virtually and in-person March 26–30, and features more than 10,000 presentations on a wide range of science topics.

“Fentanyl-class compounds account for more than 80% of opioid overdose deaths, and these compounds aren’t going anywhere — it’s just too much of an economic temptation for dealers,” says Alex Straiker, Ph.D., the project’s co-principal investigator. “Given that naloxone is the only drug available to reverse overdoses, I think it makes sense to look at alternatives.”

A new option could take one of two forms, according to Michael VanNieuwenhze, Ph.D., the other co-principal investigator for the project.

“Ideally, we would like to discover a more potent replacement for naloxone,” VanNieuwenhze says. “However, finding something that works synergistically with it, reducing the amount needed to treat an overdose, would also be a success.”

Jessica Gudorf, a graduate student in VanNieuwenhze’s group, is presenting the work at the meeting. All of the researchers are at Indiana University Bloomington.

Opioids are a class of compounds that are prescribed to treat pain and are sometimes sold illegally. If taken in excess, the drugs can interfere with breathing, making them potentially lethal. The U.S. Centers for Disease Control and Prevention estimates that more than half a million people died from overdoses involving opioids between 1999 and 2020. That toll continues to climb.

Compared to other compounds in this class, such as heroin or morphine, fentanyl and its other synthetic relatives bind more tightly to opioid receptors in the brain. Naloxone reverses an overdose by competing with the drug molecules for the same binding sites on the receptors. But because fentanyl binds so readily, it has a leg up on naloxone, and growing evidence suggests that reversing these kinds of overdoses may require multiple doses of the antidote.

At this point, researchers have exhaustively studied the strategy naloxone takes, but they have yet to find any way to improve on its performance, Gudorf says. “Our work opens the door to making new blockers that work through a different mechanism,” she explains.

Earlier research suggesting that CBD can interfere with opioid binding inspired the current effort. In research published in 2006, a group based in Germany concluded that CBD hampered opioid binding indirectly, by altering the shape of the receptor. When used with naloxone, they found CBD accelerated the medication’s effect, forcing the receptors to release opioids.

To augment these effects, Gudorf altered CBD’s structure to generate derivatives. Taryn Bosquez-Berger, a graduate student in Straiker’s group, tested these new compounds in cells with a substance called DAMGO, an opioid used only in lab studies. To measure their success, she monitored a molecular signal that diminishes when this type of drug binds. Armed with feedback from these experiments, Gudorf refined the structures she generated.

In the end, they narrowed the field to 15, which they tested at varying concentrations against fentanyl, with and without naloxone. Several derivatives could reduce fentanyl binding even at what Bosquez-Berger described as “incredibly low” concentrations, while also outperforming naloxone’s opioid-blocking performance. Two of these also showed a synergistic effect when combined with the antidote.

The team has since begun testing the most successful derivatives in mice. In these experiments, they are investigating whether these compounds alter behaviors associated with taking fentanyl.

“We hope our approach leads to the birth of new therapeutics, which, in the hands of emergency personnel, could save even more lives,” Bosquez-Berger says.

The researchers acknowledge support and funding from the Indiana University Grand Challenges Program.

A recorded media briefing on this topic will be posted Tuesday, March 28, by 10 a.m. Eastern time at www.acs.org/acsspring2023briefings. Reporters can request access to media briefings during the embargo period by contacting [email protected].

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Title
Progress towards more efficacious medicine: Antibiotics and antidotes 

Abstract
Development of innovative and efficacious medicine used for the treatment of health conditions and devastating diseases is at the forefront of pharmaceutical research as the results cannot only decrease overall drug cost, minimize adverse effects, and increase the therapeutic window, but also improve, prolong, and save lives. Globally, we are amidst severe health care crises related to bacterial resistance and opioid overdoses, which together claim millions of lives every year. Therefore, the development of more effective antibiotics and antidotes are necessary.

Antibiotic: One antibiotic that is underexplored is hypeptin, a non-ribosomal antibiotic that exhibits a broad range of activity against Gram-positive bacteria, including resistant strains, and is known to inhibit bacterial cell wall synthesis in a multifaceted approach. However, its exact mechanism(s) of action (MOA) is still unknown. To aid in elucidating its MOA, the design and progress towards the first total synthesis of hypeptin will be discussed along with activity-probing synthetic analogs.

Antidote: Naloxone, the only available antidote for opiate overdose, has a reduced therapeutic effect against fentanyl-class synthetic opioids as these potent agonists outcompete naloxone (antagonist) for the orthosteric site of the mu opioid receptor (µOR). Ergo, an alternative strategy to competitive antagonism is needed. Herein, investigations into the pharmacophore of hit compound (-)-cannabidiol (CBD) will be explored through structure activity relationship (SAR) studies with the goal of improving affinity and potency of this negative allosteric modulator (NAM). Through biological and computational efforts, fifteen of the fifty synthesized CBD analogs reversed µOR-mediated cyclic AMP inhibition induced by fentanyl, with several exhibiting much greater NAM potency than CBD. Additionally, the synergistic effects between naloxone and CBD analogs for the dissociation of fentanyl from the orthosteric site will be discussed.

Newswise — BOSTON – New research from Boston Medical Center found that substance use disorders do not increase the likelihood of dying from COVID-19. Published in Substance Abuse: Research and Treatment, the study showed that the increased risk for severe COVID-19 in people with SUD that has been seen may be the result of co-occurring medical conditions.

Multiple large cohort studies from early in the pandemic have shown higher rates of hospitalization, intubation, and death from COVID-19 in those with SUD, while other studies found no association between SUD and COVID-19-related mortality or mixed results depending on substance use pattern. Given these conflicting data, the Centers for Disease Control and Prevention has classified persons with SUD as suggestive of higher risk for severe COVID-19. The goal of this study was to assess the association between SUD and inpatient COVID-19-related mortality.

“BMC is known for excellent clinical care and innovative research related to substance use disorder. Since the early days of the pandemic, BMC has also been a leader in the treatment of individuals with COVID-19, including persons with complex medical and social needs,” said first author Angela McLaughlin, MD, MPH, an infectious disease fellow at Boston Medical Center. “These findings showing a similar likelihood of COVID-19-related complications in hospitalized patients with and without SUD helps expand knowledge of the infectious complications of SUD.” 

As BMC sees a high proportion of patients who use substances, it was an apt location for the study: almost 14% of the study population had SUD, exceeding the national average of 10.8% in people ages 18 or older. Researchers reviewed medical records of 353 adults without SUD and 56 adults with SUD admitted to Boston Medical Center early into COVID-19 pandemic and compared the likelihood of COVID-19 related complications between individuals with and without substance use disorders. They compared the relationship between COVID-19 and mortality, clinical complications, and resource utilization.

“Early in the pandemic, BMC developed protocols to closely monitor and quickly manage COVID-19-related complications in all hospitalized patients,” said senior author Sabrina Assoumou, MD, MPH, an infectious disease doctor at Boston Medical Center and Assistant Professor of Medicine at Boston University Chobanian & Avedisian School of Medicine. “The current findings suggest that such an approach might have benefited many patients, including individuals with substance use disorders.” 

In this retrospective cohort study of patients admitted to a safety net hospital during the early phase of the COVID-19 pandemic, SUD was not associated with the primary outcome of COVID-19-associated inpatient mortality. The secondary analysis showed that those with and without SUD had similar COVID-19-related clinical complications, including secondary infections, renal failure requiring dialysis, acute liver injury, venous thromboembolism, cardiac complications, and the composite “any complications.” Of note, some clinical outcomes such as stroke were very uncommon overall. Likewise, there was no difference in resource utilization secondary outcomes between the two groups. In contrast to other studies, this found similar likelihoods of mechanical ventilation and ICU admission in patients with and without SUD. Although patients with SUD presented to the hospital earlier in their disease course, their total hospital length of stay was ultimately similar to patients without SUD. Insights such as these into the clinical complications and resource utilization patterns of patients with SUD and COVID-19 can help clinicians anticipate the trajectory of infection and healthcare needs in this vulnerable group.

There were some notable limitations to the study. The results are from a single site, which might limit generalizability of the findings despite the racial and ethnic diversity of the BMC patient population. Second, the data presented are from the earliest phase of COVID-19 in the United States, so trends may have differed with subsequent waves and as COVID-19 management strategies have evolved over time. Third, there were no specific controls for socioeconomic factors like medical insurance status or income level, as over 75% of the BMC patient population has public payer insurance (Medicare, Medicaid, or Children’s Health Insurance Program) or no insurance. Lastly, differences in COVID-19 outcomes between current versus past SUD could not be detected – this area would benefit from further research.

In conclusion, in this study of hospitalized individuals at an urban safety net hospital with a diverse patient population in the early days of the COVID-19 pandemic, inpatient mortality and morbidity between patients with and without SUD were similar. The findings provide a detailed evaluation of outcomes in a unique patient population that has been disproportionately impacted by COVID-19 and may provide beneficial insights for similar settings across the country. These results point away from SUD as an independent risk factor for severe COVID-19 and further suggest a focus on medical comorbidities to mitigate the effects of COVID-19. Additional studies are needed to further evaluate for differential outcomes in this high-risk population, particularly in an era of newer COVID-19-directed therapies.

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About Boston Medical Center

Boston Medical Center is a leading academic medical center with a deep commitment to health equity and a proud history of serving all who come to us for care. BMC provides high-quality healthcare and wrap around support that treats the whole person, extending beyond our physical campus into our vibrant and diverse communities. BMC is advancing medicine, while training the next generation of healthcare providers and researchers as the primary teaching affiliate of Boston University Chobanian & Avedisian School of Medicine. BMC is a founding member of Boston Medical Center Health System, which supports patients and health plan members through a value based, coordinated continuum of care.