Category: From Newswise – Substance Abuse

Newswise — LA JOLLA, CA—An antibody in single-chain fragment variable (scFv) format that binds to the powerful opioid carfentanil was shown to reverse signs of carfentanil overdose in preclinical tests conducted by scientists at Scripps Research.

Carfentanil is a variant of the synthetic opioid fentanyl, and about 100 times as potent as its chemical cousin. Along with fentanyl and other fentanyl variants, it is commonly mixed with illegal drugs such as heroin and cocaine to enhance their euphoric effects, resulting in many fatal overdoses.

In the study, published in ACS Chemical Neuroscience on August 3, 2023, the researchers developed a human antibody that binds very tightly to carfentanil, fentanyl and other fentanyl variants. In rodents, they showed that administering a solution of the antibody shortly after an overdose reverses the potentially deadly respiratory depression caused by carfentanil, the most dangerous of the variants. The results suggest that the antibody could be a more powerful, longer-lasting treatment for synthetic opioid overdose, compared to existing options.

“We expect this antibody to be a valuable new weapon for fighting the opioid crisis,” says study senior author Kim D. Janda, PhD, the Ely R. Callaway, Jr. Professor of Chemistry at Scripps Research.

The study’s first author was Lisa Eubanks, PhD, a senior staff scientist in the Janda laboratory.

Opioid drugs, whether synthetic or derived from the opium poppy, bind and activate neuronal receptors called mu-opioid receptors. These receptors are present on different types of neurons across the human nervous system, which is why opioid drugs have multiple effects like pain-relief and euphoria, but also respiratory depression—slower and shallower breathing. Respiratory depression is the immediate cause of death in the tens of thousands of fatal opioid-related overdoses that occur each year in the U.S.

Carfentanil, after fentanyl, is the next-most common synthetic opioid found in illicit drugs in the U.S. Once available legally as a tranquilizer for large animals, it was pulled from the market by the FDA in 2018 because of its potential for misuse—and its potential lethality at doses measured in micrograms. Carfentanil is so potent that the U.S. government regards it as a possible chemical warfare agent; the Janda lab’s early work on the new antibody was funded in part by a National Institutes of Health program aimed at finding antidotes to such weapons.

Fentanyl and carfentanil overdoses currently are treated with the mu-opioid receptor-blocking drugs naloxone and naltrexone, but these treatments are sometimes ineffective against synthetic opioids even at large doses. Moreover, the benefits of these treatments typically last for less than an hour after dosing—potentially allowing respiratory depression from fentanyl or carfentanil (which persist much longer in the body) to resume.

Janda and his team set out to develop an anti-fentanyl antibody that would have three basic features: firstly, it should bind with very high affinity to fentanyl and its derivatives, pulling them out of the bloodstream and thereby causing them to diffuse out of the brain as well; secondly, it should persist in the body so as to provide reasonably long-term protection; and thirdly, it should be able to get quickly into the bloodstream and be delivered by a simple intramuscular injection, which requires no special training.

To obtain antibodies, Janda and his team vaccinated rodents with a molecule they designed that would elicit antibodies against carfentanil, fentanyl and variants. The rodents were engineered to produce human antibodies (rather than rodent antibodies, which would trigger an unwanted immune response if administered to humans). Among the resulting antibodies, the researchers were able to identify several that bind to carfentanil with super-high affinity—and bind very strongly to fentanyl and several other fentanyl derivatives. They then selected the most potent of these antibodies, modified it to be more lightweight (so that it would get quickly into the bloodstream), and further altered it so it would persist in the blood for days.

Tests in rodents showed that the optimized scFv, dubbed C10‐S66K, did indeed have a powerful effect at reducing carfentanil’s actions on the brain—reversing carfentanil-driven respiratory depression when injected 15 minutes after a heavy carfentanil exposure. The effect after about 40 minutes was stronger than naloxone’s and was still increasing after two hours, whereas naloxone’s peaked at 30 minutes and swiftly declined.

As part of the study, the collaborating laboratory of Ian Wilson, PhD, Hansen Professor of Structural Biology at Scripps Research, used X-ray crystallography to determine the near-atomic resolution structures of carfentanil- and fentanyl-bound C10‐S66K. These structural data suggest that the antibody should indeed bind well to multiple fentanyl derivatives but should not interfere with the activity of other beneficial opioid molecules such as naloxone and naltrexone.

Janda and Scripps Research have licensed the rights to further develop and market C10-S66K to the pharma company Cessation Therapeutics, the sponsor of the clinical trial planned for this month. The U.S. Food and Drug Administration (FDA) has approved a full length IgG version of this antibody termed CSX-1004 for clinical trials, slated to begin this month for the prevention of fentanyl overdose.

“An Engineered Human-Antibody Fragment with Fentanyl Pan-Specificity that Reverses Carfentanil-Induced Respiratory Depression” was co-authored by Lisa Eubanks, Tossapol Pholcharee, David Oyen, Yoshihiro Natori, Bin Zhou, Ian Wilson and Kim Janda, all of Scripps Research.

Funding for the study was provided in part by the National Institute on Drug Abuse (U01DA046323).

Newswise — More than 10 million Americans misused prescription opioids in 2019, and nearly 75 percent of drug overdose deaths in 2020 involved an opioid. According to the United States Centers for Disease Control and Prevention, overdose deaths involving opioids, including prescription opioids, heroin and synthetic opioids such as fentanyl, have increased eightfold since 1999.

As scientists and the health care community search for effective ways to mitigate the opioid epidemic, rapid advances in machine learning are promising. Access to data and machine learning frameworks has led to the development of machine learning models that use health care data to deal with different facets of the opioid crisis. For example, health care databases can assist researchers and clinicians to identify patients at risk by leveraging various data and information.

But are these machine learning models built on health care data reliable at predicting opioid use disorder? That’s what researchers from Florida Atlantic University’s College of Engineering and Computer Science wanted to explore. As such, they examined peer-reviewed journal papers and conducted the first systematic review analyzing not only the technical aspects of machine learning applied to predicting opioid use, but also the published results.

Their goal was to determine if these machine learning methods are useful and, more importantly, reproducible. For the study, they reviewed 16 peer-reviewed journal papers that used machine learning models to predict opioid use disorder and investigated how the papers trained and evaluated these models.

Findings, published in the journal Computer Methods and Programs in Biomedicine, reveal that while results from the reviewed papers show machine learning models applied to opioid use disorder prediction may be useful, there are important ways to improve transparency and reproducibility of these models, which will ultimately enhance their use for research.

For the systematic review, researchers searched Google Scholar, Semantic Scholar, PubMed, IEEE Xplore and Science.gov. They extracted data that included the study’s goal, dataset used, cohort selected, types of machine learning models created, model evaluation metrics, and the details of the machine learning tools and techniques used to create the models.

Findings showed that of these 16 papers, three created their dataset, five used a publicly available dataset and the remaining eight used a private dataset. Cohort size ranged from the low hundreds to more than half a million. Six papers used one type of machine learning model, and the remaining 10 used up to five different machine learning models. Most papers did not sufficiently describe the machine learning techniques and tools used to produce their results. Only three papers published their source code.

“The reproducibility of papers using machine learning for health care applications can be improved upon,” said Oge Marques, Ph.D., co-author and a professor in FAU’s Department of Electrical Engineering and Computer Science. “For example, even though health care datasets can be hindered by privacy laws and ethical considerations, researchers should follow machine learning best practices. Ideally, the code should be publicly available.” 

The researchers’ recommendations are threefold: use the area under the precision/recall curve (AUPRC), a metric more useful in cases of imbalanced datasets when the negative class is more prevalent and there is low value in true-negative predictions; and avoid non-interpretable models (also known as “black-box models”) in this critical health care area, and favor using interpretable models whenever possible. If that is not possible and a non-interpretable model must be deployed to predict opioid use disorder, they recommend defining the reasons that justify its use. Finally, to ensure transparency and reproducibility of results, the researchers recommend the adoption of checklists and other documentation practices before submitting machine-learning-based studies for review and publication. Better documented and publicly available studies will help the research community advance the field.  

The researchers note that the lack of good machine learning reproducibility practices in the papers makes it impossible to verify their claims. For example, the evidence presented may fall short of the accepted standard, or the claim only holds in a narrower set of circumstances than asserted.

“Journal papers would be more valuable to the research community and their suggested application if they follow good practices of machine learning reproducibility in order for their claims to be verified and used as a solid base for future work,” said Marques. “Our study recommends a minimum set of practices to be followed before accepting machine-learning-based studies for publication.”  

Study co-authors are Christian Garbin, first author and a Ph.D. candidate, and Nicholas Marques, an M.S. student in data science and analytics and a National Science Foundation Research Traineeship Program scholar, both within the College of Engineering and Computer Science.

“Opioid use disorder is a public health concern of the first magnitude in the United States and elsewhere,” said Stella Batalama, Ph.D., dean, FAU College of Engineering and Computer Science. “Harnessing the power and potential of machine learning to predict and prevent one’s risk of opioid use disorder holds great promise. However, to be effective, machine learning methods must be reliable and reproducible. This systematic review by our researchers provides important recommendations on how to accomplish that.”

– FAU –

About FAU’s College of Engineering and Computer Science:

The FAU College of Engineering and Computer Science is internationally recognized for cutting-edge research and education in the areas of computer science and artificial intelligence (AI), computer engineering, electrical engineering, biomedical engineering, civil, environmental and geomatics engineering, mechanical engineering, and ocean engineering. Research conducted by the faculty and their teams expose students to technology innovations that push the current state-of-the art of the disciplines. The College research efforts are supported by the National Science Foundation (NSF), the National Institutes of Health (NIH), the Department of Defense (DOD), the Department of Transportation (DOT), the Department of Education (DOEd), the State of Florida, and industry. The FAU College of Engineering and Computer Science offers degrees with a modern twist that bear specializations in areas of national priority such as AI, cybersecurity, internet-of-things, transportation and supply chain management, and data science. New degree programs include Master of Science in AI (first in Florida), Master of Science and Bachelor in Data Science and Analytics, and the new Professional Master of Science and Ph.D. in computer science for working professionals. For more information about the College, please visit eng.fau.edu. 

About Florida Atlantic University: Florida Atlantic University, established in 1961, officially opened its doors in 1964 as the fifth public university in Florida. Today, the University serves more than 30,000 undergraduate and graduate students across six campuses located along the southeast Florida coast. In recent years, the University has doubled its research expenditures and outpaced its peers in student achievement rates. Through the coexistence of access and excellence, FAU embodies an innovative model where traditional achievement gaps vanish. FAU is designated a Hispanic-serving institution, ranked as a top public university by U.S. News & World Report and a High Research Activity institution by the Carnegie Foundation for the Advancement of Teaching. For more information, visit www.fau.edu.

Newswise — ANAHEIM—Two studies featured today at the 2023 AACC Annual Scientific Meeting & Clinical Lab Expo highlight advances that could boost the accuracy of marijuana tests and provide vital information for addressing the opioid epidemic. The first describes a promising method for determining when urine samples have been tampered with to evade a positive result for marijuana. The second found that more than half of fentanyl samples contained novel psychoactive substances that could heighten the drug’s danger. 

The legalization of marijuana in many states and the emergence of the fentanyl crisis have underscored the need for accurate and reliable drug tests. As marijuana use becomes more prevalent, researchers are focused on improving the detection methods used for legal, medical, and workforce drug tests. For example, many labs want help identifying when urine samples have been manipulated to avoid a positive result for marijuana. 

Deaths from opioid overdoses have been steadily climbing in the U.S. since 2020, in part due to the spread of the powerful narcotic fentanyl. At the same time, there has been a rise in the prevalence of novel psychoactive substances, which are often added to drugs sold as fentanyl to enhance potency. These substances can raise the risk of overdose and death.

“Dilute-and-Shoot” Method Detects Manipulated THC Samples

A scientific team led by Yubo Chai, MD/PhD, at the Mayo Clinic in Rochester, Minnesota, devised a method to counteract the drug-masking effects of common adulterants in marijuana tests. The researchers gathered 5 urine samples positive for both delta 8- and 9-THC-COOH, which are active ingredients of cannabis. They treated them with the adulterant nitrite or strong acid adulterants and found that the compounds quickly degraded both of the ingredients and the internal standard.

The team then implemented a “dilute-and-shoot” workflow that combines a tandem- mass spectrometry method and liquid chromatography separation system. The system can determine whether a urine sample is truly negative or only appears so because it has been degraded by nitrite. The method was further validated with an additional crop of 12 specimens that contained delta 8-THC-COOH, delta 9-THC-COOH, or both.

“Our unique dilute-and-shoot method can separate and quantify delta 8- and 9-THC-COOH,” Chai said. “As a result, labs will be able to distinguish between true negative delta 8- and 9-THC-COOH results from specimens adulterated with nitrite, as the latter lack peaks for both the analytes and the internal standard.”

Chai noted that their study only tested samples adulterated with sodium nitrite. He calls for further work with samples tainted with other compounds such as peroxide and potassium nitrite. 

Study Sheds Light on “Designer” Substances in Fentanyl 

In another study, a group led by Gemma Campbell at Aegis Sciences Corp. in Nashville set out to evaluate how common novel psychoactive substances are in fentanyl tests. Studying 200 urine and oral fluid samples gathered from individuals in 30 U.S. states who tested positive for fentanyl, the scientists performed additional testing for designer opioids, benzodiazepines, synthetic marijuana, and other substances.

Strikingly, 117 of the samples (58.5%) tested positive for at least one novel psychoactive substance. Almost 38% of the samples tested positive for xylazine, which possesses opioid-like effects but can’t be reversed by naloxone, a life-saving medication that blocks the effects of opioid overdose. Nearly half (47%) of the samples contained other designer opioids, and 8% tested positive for designer benzodiazepines, which can prove deadly when combined with opioids outside of medical settings.

“The timeliest finding as it relates to the danger of today’s illicit drug supply was finding xylazine in 38% of the fentanyl samples,” said study scientist Andrew Holt, Pharm.D, at Aegis Sciences Corp.

“Depending on where drug testing occurs, an understanding of the other substances present in the illicit drug supply can change the approaches to harm reduction with communities and individuals,” he added.

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About the 2023 AACC Annual Scientific Meeting & Clinical Lab Expo

The 2023 AACC Annual Scientific Meeting offers 5 days packed with opportunities to learn about exciting science from July 23-27 in Anaheim, California. Plenary sessions will explore microbiome-directed therapies for undernutrition, big data for practicing precision medicine, healthcare equity, cardiovascular disease in women, and promising sickle cell disease treatments.

At the Clinical Lab Expo, more than 900 exhibitors will fill the show floor of the Anaheim Convention Center in Anaheim, California, with displays of the latest diagnostic technology, including but not limited to COVID-19 testing, artificial intelligence, point-of-care, and automation.

About the Association for Diagnostics & Laboratory Medicine (ADLM) Dedicated to achieving better health through laboratory medicine, ADLM (formerly AACC) brings together more than 70,000 clinical laboratory professionals, physicians, research scientists, and business leaders from around the world focused on clinical chemistry, molecular diagnostics, mass spectrometry, translational medicine, lab management, and other areas of progressing laboratory science. Since 1948, ADLM has worked to advance the common interests of the field, providing programs that advance scientific collaboration, knowledge, expertise, and innovation. For more information, visit www.myadlm.org. 

Newswise — Greensboro, NC (March 22, 2023) – Shenzhen Superbio Technology Co., LTD. (Superbio) has received clearance from the US Food and Drug Administration (FDA) on the first ever point-of-care instrument intended for qualitative detection of fentanyl in human urine and has fully released authorization to Bioeasy USA, Inc.(Bioeasy) of this product in the United States of America. Carolina Liquid Chemistries Corp. (CLC), a leading provider of chemistry analyzers and reagents for drug testing and general chemistry testing for over 25 years, has partnered with Bioeasy and will be the distributor of the product in the USA under the brand name RYAN™.

The Carolina Liquid Chemistries Corp. Fentanyl Urine Detection Kit is a fluorescence immunoassay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL. The assay is intended for use with Carolina Liquid Chemistries Corp. immunofluorescence analyzer RYAN. The test provides a preliminary test result; a more specific alternative chemical method must be used in order to obtain a confirmed analytical result.

The Carolina Liquid Chemistries Corp. immunofluorescence analyzer RYAN is a portable fluorescence instrument for in vitro diagnostic use only. The analyzer is designed to perform in vitro diagnostic tests on clinical urine specimens. This analyzer can be used in a laboratory or in a point-of-care setting.

Fentanyl is a potent narcotic analgesic and is a kind of special opioid receptor excitant. Fentanyl is one of the varieties under the supervision of the United Nations Single Convention on Narcotic Drugs of 1961. Fentanyl is one of the most common drugs used for treating moderate and severe pain. After continuous injections with fentanyl, patients will have symptoms of opioid withdrawal syndrome such as ataxia and testiness. Patients that have taken fentanyl for a long time may become addicted. Fentanyl is mainly transformed biologically in the liver and forms various metabolic products without pharmacological activity. About 75% of these metabolic products are excreted with urine, about 10% are excreted with urine in original form, and a few are excreted with feces and bile.

The Ryan analyzer with the Carolina Liquid Chemistries Corp. Fentanyl Urine Detection Kit uses the principle of competitive and fluorescence immunochromatography assay and uses fluorescence microspheres-labeled monoclonal antibody as the indicator marker to qualitatively detect fentanyl in human urine.

“We are very proud of the work that our partner Bioeasy and its consultants have done to bring this product to market,” says Paticia Shugart, COO of Carolina Liquid Chemistries Corp. “Physicians can have results in under 6 minutes. This is a game changer.”

“To achieve as low as a 1ng/ml cutoff is very challenging, and I’m very pround that our R&D team made a great technical breakthrough,” says Elaine Zhang, the General Manager of Bioeasy USA. Ms. Zhang continued, “Now that the abuse of Fentanyl use has been causing serious problems, I deeply hope this product can help to fight the drug threat in the USA!”

To learn more about the products and services offered by Carolina Liquid Chemistries Corp. including clinical chemistry analyzers, general chemistry, special chemistry, drug testing reagents, and COVID-19 test kits and supplies please visit carolinachemistries.com.

About Carolina Liquid Chemistries Corp.

Carolina Liquid Chemistries Corp. (CLC), a certified Veteran Owned Business headquartered in Greensboro, NC, has its reagent production facility located in Brea, CA. This ISO certified facility is an FDA registered, manufacturer, re-packager, re-labeler, and value-added reseller of chemistry systems and reagents for general chemistries and urine drug tests. CLC helps clinical laboratories of all sizes reduce chemistry analyzer and reagent costs while also receiving accurate and timely results. The company has responded to the COVID-19 pandemic by providing various testing products and supplies to market under the FDA’s Emergency Use Authorization. For more information, call 877-722-8910 x103, visit carolinachemistries.com, or email [email protected].

About Bioeasy USA, Inc.

Bioeasy USA, Inc, located in La Verne, CA, is a wholly-owned subsidiary of Shenzhen Bioeasy Biotechnology Co., Ltd (Stock Code: 300942), who is dedicated to R&D, manufacturing and sales & marketing of POCT IVD products ranging from lateral flow rapid testing to POCT Chemiluminecense (CLIA)products for years. Bioeasy USA focuses on toxicology market in US, providing comprehensive drug testing portfolio covering instant urine/oral fluid testing solutions. With a wide range of drug panels, including the popular drugs of fentanyl, oxycodone, tramadol, K2, gabapentin and more, Bioeasy USA DOA products can widely serve different practice segments.

Whether you’re a licensed therapist, a psychiatric doctor, or a curious reader, you’ll enjoy these recent research headlines in the fields of psychology and psychiatry. 

Hobbies and Healthy Habits Surged During the Pandemic

-Rutgers University-New Brunswick

‘I feel like I’m suffocating’: what’s driving suicidal thoughts in the Australian construction industry?

-University of South Australia

ADHD Behind the Wheel: Ways to Keep Teen Drivers Safe

-Saint Louis University Medical Center

How effective is Functional Family Therapy for addressing youth behavior problems?

-Wiley

UTHealth Houston study on seasonality of teen suicidality in JAMA Network Open

-University of Texas Health Science Center at Houston

Bipolar disorder linked to 6-fold heightened risk of early death from external causes

-BMJ

CSUF Study Examines Ways to Deter Cheating Online

-California State University, Fullerton

Training staff on low intensity psychological interventions for mental health conditions can cut workplace sickness

-Swansea University

Study Shows Differences in How Patients With Heroin Use Disorder Process Drug and Reward Cues

-Mount Sinai Health System

Men ‘less satisfied with life’ when their female partner is the only earner – new study

-University of Bath

Positive contact with diverse groups can reduce belief in conspiracy theories about them

-University of Nottingham

Significant rise in ADHD diagnoses in the UK

-University College London

In determining what’s true, Americans consider the intentions of the information source

-Boston College

Political Apathy Spreads from Parents to Adolescent Children

-Florida Atlantic University

Newswise — Rather than turn to vices such as alcohol and drugs, many people turned to new pursuits to cope with pandemic-related stresses, according to a Rutgers study.

The study, published in the journal Drug and Alcohol Dependence, paints a more nuanced picture of how Americans adjusted to stay-at-home orders over the course of the pandemic.

“Reporting more types of negative experiences across work, home and social domains was associated with reporting more positive types of pandemic experiences, such as increasing physical activity and exercise, spending more time outdoors or engaging in hobbies, having time to cook to improve diet and nutrition, and spending more time with family and friends (even if virtually),” the researchers wrote. This suggests that many individuals may have adapted to the negative pandemic impacts by adjusting behavioral lifestyle habits and engaging with social supporters.

To measure the effects of pandemic-related emotional, physical and economic stressors on substance use frequency, researchers at the Rutgers Center of Alcohol and Substance Use Studies examined data from the Caltech’s COVID-Dynamic project.

As part of the COVID-Dynamic survey, participants were asked a series of questions about pandemic-related experiences, including physical and emotional health, employment, finances and family. They also were asked about their monthly substance use and whether the pandemic had any positive effects on their lives – such as increases in exercise or more attention to diet.

By examining data from two waves of the COVID-Dynamic project (July 2020 and January 2021), Rutgers researchers, working with colleagues from three other institutions at Kaiser Permanente and the City College of New York, determined how substance use was linked to pandemic-related experiences.

For instance, people reporting social and emotional impacts from the pandemic were more likely to use alcohol, while those reporting economic hardship were less likely to drink.

By contrast, nicotine use was higher among those reporting economic impacts and lower for people reporting significant social impact. Cannabis use was positively associated with emotional hardship.

Perhaps the most surprising finding was the dearth of substance use among the study participants, the researchers said.

“Overall, the amount of substance use in this sample was relatively low,” said Denise Hien, Director of the Center of Alcohol and Substance Use Studies, a distinguished professor in the Rutgers Graduate School of Applied and Professional Psychology (GSAPP), and coauthor of the study.

“We often think in terms of collective trauma, but this sample upends the idea that the pandemic was universally impactful,” said Alexandria Bauer, an assistant research professor and a coauthor of the study. Particularly for a normative population, “the data show there’s a lot of nuances in how people experience these kind of mass events.”

“While some data has shown that the use of drugs and alcohol increased during the COVID-19 pandemic, we found that many also coped during its darkest days by doing healthy activities like cooking, reading and gardening,” said Margaret Swarbrick, associate director and professor, Center of Alcohol and Substance Use Studies in the Graduate School of Applied and Professional Psychology. “Engagement in health habits and hobbies appeared to increase to cope with the negative impacts of the pandemic, demonstrating that many were resilient.”

“This study demonstrates GSAPP’s ongoing commitment to conducting relevant, cutting-edge research for the common good,” Arpana G. Inman, Dean and Distinguished Professor, Graduate School of Applied and Professional Psychology.

Newswise — According to the Centers for Disease Control, 100,000 Americans die each year from an overdose, most due to the use of synthetic opiates like fentanyl. While naloxone, currently the only antidote for opiate overdose, has become more common, it is less effective against fentanyl-class synthetic opioids.

Researchers at Indiana University have identified a new method of reversing the effects of fentanyl, which is 50 to 100 times stronger than morphine. Their study, published in the Journal of Medicinal Chemistry, could lead to a new way to reverse overdoses either through a new product or working synchronously with naloxone.

“The synthetic opiates bind very tightly to the opioid receptors,” said Alex Straiker, senior research scientist for the Gill Center for Biomolecular Science. “Naloxone must compete with opioids for the same binding site in the central nervous system to cancel out an overdose. But during a fentanyl overdose, naloxone and fentanyl bind to different sites, meaning there is no competition. We wanted to see if a negative allosteric modulator could reverse the fentanyl effects.” 

Straiker began measuring the effect of opioid receptors on a signaling molecule called cAMP. Fifty structurally related molecules were tested chemically to identify which compounds showed the most promise to be an effective negative allosteric modulator.

Researchers found cannabidiol, or CBD, could behave as a negative allosteric modulator at the binding site. However, high concentrations were necessary during initial testing. Researchers modified the cannabidiol structure to be more effective and found that in the in vitro – tests done on blood or tissue samples – diagnostics, it successfully reversed the effects of fentanyl. 

“We’ve identified structural parts that are important for the desired antidote effect,” Straiker said. “Some of these compounds are much more potent than the lead. We’ve worked with a third lab to model the binding site that may help identify additional compounds moving forward.”

The next step is testing their findings in vivo, meaning on living organisms, to determine if it reverses respiratory depression which is the main overdose effect.

Additional authors on the study were Taryn Bosquez-Berger, IU Bloomington Psychological and Brain Sciences Ph.D. candidate, Jessica A. Gudorf, IU Bloomington graduate student in organic chemistry, Charles P. Kuntz, Jonathan P. Schlebach, assistant professor of chemistry at IU Bloomington and Michael S. VanNieuwenhze, Standiford H. Cox Professor of chemistry at IU Bloomington. 

Newswise — New York, NY (July 18) – An Icahn School of Medicine at Mount Sinai study sheds new light on some of the underlying neurobiological mechanisms of opioid addiction, which accounted for three-quarters of the more than 100,000 fatal drug overdoses in the United States in 2021.

The Mount Sinai researchers found that inpatients with heroin use disorder exhibited a bias in favor of processing drug cues over cues related to natural, non-drug rewards, as observed during passive viewing of the cues and when the patients were asked to try two emotional regulation strategies. Results of the study were published in the July 12 issue of the American Journal of Psychiatry.

For this study, researchers used functional magnetic resonance imaging (fMRI), an imaging scan that shows activity in a specific area of the brain, to track blood oxygenation in real time while individuals looked at drug-related, neutral, and food images. Since brain cells use more oxygen when active, the fMRI signals areas of the brain that “light up” when most active.

The research team found that in individuals with heroin use disorder, responses to drug cues (images of individuals using or simulating use of drugs or of drug paraphernalia) were enhanced in brain regions associated with reward and inhibitory control, while these individuals’ brain regions were less reactive to food or neutral images (e.g., stapler) when compared to healthy control subjects.

Although there were no group differences during the two emotional regulation strategies (aimed at decreasing drug-related reactions and enhancing natural reward-related reactions) when inspected separately, significant differences between the groups emerged when the two strategies were considered together. One of the emotional regulation strategies—cognitive reappraisal—involved re-evaluating the significance of the drug cues (e.g., imagining that the drugs in the pictures are not real, or that the people in the images are actors). The other emotional regulation strategy—savoring—involved enhancing the significance of the food cues (e.g., imagining holding, eating, and enjoying the food pictured).

Compared to healthy controls, participants with heroin use disorder showed enhanced cortico-striatal reactivity when reappraising drug cues compared to when savoring food cues, with healthy controls showing the opposite pattern.   

“In heroin addiction, the effort to downregulate response to drug cues via reappraisal may come at the expense of the ability to upregulate healthy hedonic responses, depleting the cognitive-affective resources needed to enjoy natural, nondrug rewards,” said Yuefeng Huang, PhD, a postdoctoral fellow in psychiatry at the Icahn School of Medicine at Mount Sinai and first author of the study.

These findings suggest that inpatients who are in the early stage of treatment for heroin-use disorder possess the neural resources to modulate their emotional responses to drug and food cues. However, in these individuals the neural resources needed to suppress responses to drug cues appear to come at the cost of the ability to amplify responses to healthy reward stimuli, which may diminish the resources necessary to derive enjoyment from natural, non-drug rewards. Conversely, healthy controls who do not have addiction demonstrated the opposite pattern, pinpointing an important target for intervention to normalize function.

“This study paves the way for testing interventions to normalize these deficits, reduce craving, and enhance recovery in drug addiction, including via cognitive reappraisal and savoring in mindfulness-oriented recovery enhancement, non-invasive brain stimulation, and/or pharmacologically,” adds Rita Z. Goldstein, PhD, senior author of the study and Professor in Neuroimaging of Addiction at the Icahn School of Medicine at Mount Sinai.

The study team is currently collecting longitudinal data from the participants of the study who were scanned again after 15 weeks of treatment to investigate potential recovery effects. They are also planning to increase the recruitment of women to investigate sex differences in the patterns identified in the study, since the current sample size was small and predominantly men.

About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, over 400 outpatient practices, nearly 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advanced health for all people, everywhere, by taking on the most complex health care challenges of our time — discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it. 

Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. We are consistently ranked by U.S. News & World Report‘s Best Hospitals, receiving high “Honor Roll” status, and are highly ranked: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. U.S. News & World Report’s “Best Children’s Hospitals” ranks Mount Sinai Kravis Children’s Hospital among the country’s best in several pediatric specialties.

For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.

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Newswise — INDIANAPOLIS—An estimated 16 million people in the United States have alcohol use disorders (AUDs), according to the National Institutes on Alcohol Abuse and Alcoholism (NIAAA). Now, Indiana University researchers have made a substantial discovery in the role genes play in the development of AUDs, finding that alteration of a group of genes known to influence neuronal plasticity and pain perceptions, rather than single gene defect, is linked to AUDs.

“We know inherited genes are a major contributor to this disease, because past studies have shown family genetics to be directly associated with alcohol dependence within a family,  such as identical twins raised in different environments,” said Feng Zhou, PhD, professor emeritus of anatomy, cell biology and physiology at IU School of Medicine.

Zhou is the lead author, along with William Muir, PhD, professor emeritus of genetics at the Purdue Department of Animal Sciences, of a new publication in Alcohol: Clinical and Experimental Research which details their new findings.

Researchers used three different animal models created in the IU Alcohol Research Center to study how the genes impact desire for alcohol. The study involved statistically sorting through about 3 billion DNA base pairs containing nearly 30,000 genes, in 70 individual animals to identify the handful that were responsible for drinking behaviors. Thanks to their experimental design, the researchers could identify population differences based on drinking behaviors rather than chance genetic differences or other environmental influences.

“These rat models are all uniquely qualified as criteria for human outcomes,” said Zhou.

The genes that mediate pain sensation act in concert with two other groups of neural channel and neural excitation genes which perform neural communication functions, the team found.

“The function of these three groups of genes is important for neuroadaptation and neuroplasticity, meaning that they can change brain communications,” Zhou said.

They also discovered a key cohort of genes impacted alcohol use, with some of the genes having silent mutations, meaning they did not alter the amino acid sequence translated, but influenced the rate and conformation of gene transcription, causing changes in the other genes that had an impact on alcoholism.

“This is the first time these multiple models have ever been used for this pursuit,” Muir said. “In the past, research has focused on a single gene and how it can contribute to alcohol use, but now, we can see that these large groups of genes make a difference, which can help guide future research and clinical care for those suffering from AUDs.”

“The brain must be modified over the drinking period. That kind of modification is similar to drug abuse,” Zhou said. “It is genetically prone neural plasticity or neural adaptation to a certain level that makes drinking more pleasurable and more tolerable, or pain relief.”

“The alleviation of pain appears to be one motivation to drink and continue to drink,” Muir said. “Knowing that, it’s possible that early counseling can produce drinking avoidance.”

The new findings raise the possibility of genetic testing for alcoholism. People who get tested and know that they have a high genetic tendency to become an alcoholic might take extra care to moderate their drinking.

“One future direction is how these animal findings would translate to humans,” Zhou said. “If verified, then treatment or prevention can be more focused.”

Other study authors include Chiao-Ling Lo, PhD and Richard Bell, PhD of IU School of Medicine and the Indiana Alcohol Research Center at IU School of Medicine.

About IU School of Medicine

IU School of Medicine is the largest medical school in the United States and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.

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