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Newswise — Data from the Centers for Disease Control and Prevention show there were about 107,000 drug overdose deaths in the United States in 2023. Of those, about 75 percent, or 81,000, involved opioids.

Lauren Jones ’22.

With the aim of reducing those statistics, Lauren Jones ’22, who is in a post-baccalaureate at Harvard University, Brenna Outten ’22, a third-year doctoral student at Caltech and Leah Juechter ’24, who is working temporarily as a medical assistant, used computational chemistry as undergraduates at Furman to study the impacts of synthetic opioids.

Their work, with collaborators at Hendrix College and California State University, Los Angeles, was published in December in The Journal of Physical Chemistry B.

To say the project was formative for Jones and Outten is an understatement. They laid the foundation for the study during the height of COVID when traditional wet labs were all but shuttered.

“It’s amazing we were able to continue the work virtually during the pandemic,” said Jones, who researches sensory processing in children with autism and brain activity in children with rare neurodevelopmental and neurogenetic disorders at Boston Children’s Hospital.

Outten said the project “opened my eyes to how a scientist can contribute to fields like neuroscience, chemistry, biology and physics in ways I had never considered before.”

The paper focuses on work targeting the mu opioid receptor, or MOR. It resides mainly in the central nervous system and the GI tract. It’s like a molecular lock waiting for the right key (a drug like morphine or fentanyl) to unlock or activate a favorable response, such as reduced pain signals. But the same drugs can activate negative responses like drug tolerance, constipation, respiratory depression, addiction and overdose.

“There’s a lot we don’t understand about how opioids interact with the receptors embedded on nerves that mitigate the pain-signaling process,” Juechter said. “So the more we can uncover about how these drugs are interacting with the receptors in our bodies and the responses we feel, the better we’re able to help create pain therapeutics with reduced adverse effects and more beneficial safety profiles.”

What makes the researchers’ study unique is the application of both quantum mechanics conducted by Juechter, Outten and Jones, led by chemistry Professor George Shields, and molecular dynamics carried out by teams at Cal State and Hendrix College.

“It was interesting to see two drugs (morphine and fentanyl) that elicit almost identical effects are binding to the receptor in completely different ways,” Juechter said. “And to demonstrate that with highly accurate quantum mechanics was one of the first times we’ve seen that done.”

Leah Juechter ’24.

The manner in which opioids bind to MOR is diverse and complex. “So the need for a precise computing model becomes essential,” Juechter explained. “Even slight variations in calculations can drastically affect the data and subsequent conclusions.”

The ability to do research computationally can make drug development faster and cheaper, Juechter added. “Being able to paint the picture of what’s going on using empirically-supported mathematical theories, we can streamline the initial process of drug development.”

Impactful undergraduate research is a hallmark of The Furman Advantage, a four-year approach to education that creates a pathway for students to determine who they want to be and how they want to contribute to the world once they leave the university.

Juechter spent about eight months post-graduation fine-tuning the work with her coauthors before the paper was published.

“It was exceedingly evident Dr. Shields wanted to elevate me and give me the opportunity to pursue research,” Outten said.

Juechter hopes the project will set the tone for organic chemists involved in drug research and development.

“I want a role in the health care industry because I like the idea of affecting someone’s life in real time, in a positive way,” she said.

While researchers have long spotlighted the role childhood abuse, poverty, and substance use play in human development, Virginia Tech’s Jungmeen Kim-Spoon is pulling back the curtain on what actually happens inside the brains of the young adults affected. 

For the past 10 years, Kim-Spoon and her colleague Brooks Casas have co-led a research team that has tracked the brain function of teens. They found adolescents who experienced early life adversity showed unusual brain activity during tasks that require focus and self-control. This finding suggests delayed development in certain areas of the brain, which is linked to higher risks for mental health disorders in early adulthood and future substance use. 

“Our findings show that early adverse experiences not only predict and impact mental health such as depression and anxiety, but also affect brain development,” said Kim-Spoon, professor of psychology. 

The first-of-its-kind study recently resulted in two published journal articles, one in Development and Psychopathology and another in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. The former discusses findings related to maltreatment, brain development related to cognitive control, and psychopathology. The latter focuses on connectivity between neural circuits of the brain as a predictor of substance use initiation. 

Jungmeen said that despite the well documented connection between adverse experiences and the development of mental health disorders, the lack of available information on exactly how adolescents are impacted internally motivated the research. 

“By age 18, more than half of adults in the United States have experienced at least one type of adversity,” said Kim-Spoon, who is also director of the JK Lifespan Development Lab at Virginia Tech. “Yet our understanding about how adverse experiences may alter the ways in which the brain and nervous system change over time, increasing vulnerability to mental health and substance use disorders, remains vastly insufficient.”   

She and her collaborators set out to investigate this by recruiting adolescents from rural, suburban, and urban communities in Southwest Virginia, North Carolina, Tennessee, and West Virginia in 2014. Over 10 years, they tracked participant brain function, neural precursors – neurobiological markers in the developing brain – and other developmental check points through annual MRI scanning, questionnaires, and neurocognitive testing. 

The research team includes: 

Participants’ family dynamics, decision-making skills, substance use initiation and frequency, personality factors, and social relationships were also assessed yearly with the goal of providing a well-rounded view of the factors impacting the adolescents.

“Jungmeen and I get to tackle thorny problems while pursuing answers to questions that matter for promoting healthier youth development,” Deater-Deckard said. “Our team utilizes state-of-the-art quantitative modeling techniques to integrate complex arrays of data from many sources such as surveys, observations, and brain imaging. She has helped me understand the complex changes in health and functioning over time.”   

Researchers also annually observed adolescents with no prior history of substance use in the same study sample from ages 14 to 21 over a period of seven years. Their findings suggest brain connectivity — the pattern of connections between different parts of the brain — rather than cognitive control behavior — the ability to adapt your behavior to meet your goals, and to override automatic responses — was the stronger predictor of future substance use.

Specifically, stronger connectivity between the dorsal anterior cingulate cortex and the dorsolateral prefrontal cortex — two brain regions that are crucial to cognitive control — was associated with delayed substance use onset, and this connectivity pattern showed a significant drop one year prior to substance use initiation.

Some of the group’s findings also illustrate the brain’s resiliency. Although cognitive control brain functioning is delayed in early adolescence following childhood maltreatment, the findings suggest it often “catches up” during middle to late adolescence, suggesting neural plasticity and opportunities to help these young people. 

“By conducting more research on neural plasticity during adolescence, we can shed light on the brain’s potential as a target for preventive interventions, aimed at promoting resilient functioning in young people facing adversity,” Kim-Spoon said.

Fueled by these results and supported by several grants from the National Institutes of Health to Kim-Spoon and Casas as well as the Virginia Tech Institute for Society, Culture and Environment, Kim-Spoon and the research team plans to continue this study for another five years. As the participants enter their 20s, the team will focus more on examining their relationships, networks, and social environments to understand how they contribute to the ways young people navigate unique challenges in early adulthood.    

“This longitudinal project has been very rewarding especially in terms of collaborating with brilliant minds within Virginia Tech and outside,” Kim-Spoon said. “It has been fun to look into the things we can do to help young people develop healthier, and it will be interesting to see what we will find in the next few years.”   

By expanding this research, Kim-Spoon and her collaborators can contribute to the development of effective resilience and protective strategies to help people at higher risk of developing mental health and addiction problems improve their future well-being. 

Kim-Spoon said she believes we are just beginning to better understand the factors affecting young people’s mental health, substance use, and well-being by examining how brain function and development interact with social and emotional dynamics, and spirituality.

“Adverse experiences, no matter how we view them, are tough, but there are things we can do to help these young people develop healthier, such as access to parental support, education, and positive experiences with peer groups,” Kim-Spoon said.

Original study DOI:10.1017/S0954579424000531

Original study DOI:10.1016/j.bpsc.2024.11.020

Newswise — People seeking online support for addiction recovery may encounter cynical marketing by the addiction treatment industry that sometimes prioritizes financial gain over clients’ health and well-being, according to a study of public discourse around substance use recovery on Twitter. Among people trying to quit or reduce their use of alcohol or other substances, engagement with clinical treatment remains low. More typically, people with alcohol use disorder (AUD) or other substance use disorders (SUDs) seek community-based mutual-help groups (such as Alcoholics Anonymous, Narcotics Anonymous, or SMART Recovery). Since the COVID-19 pandemic, online recovery supports have become a central piece of recovery efforts for many. Forums that offer access to peer support and accountability include virtual mutual-help group meetings, social networking sites focused on recovery, and traditional social media (e.g., Reddit). For the study in Alcohol: Clinical & Experimental Research, US investigators examined how Twitter, a social network site since renamed X, was used for AUD and SUD recovery support.

The researchers used large-scale data analytics to collect tweets posted in English during 2022 that contained certain keywords and hashtags relating to substance use recovery (e.g., #recovery, #sober, #wedorecover, #alcoholicsanonymous, #harmreducation). They retained 186,460 tweets addressing 18 relevant topics. A random 100 tweets from each topic group—1,800 posts—were manually examined and categorized by certain attributes, including source and theme. After filtering for relevance and other criteria, the researchers used statistical analysis to explore the attributes and themes of 1,132 tweets on substance use recovery.

These tweets were posted by individuals in or seeking recovery (42%), the addiction treatment industry (21%), general individuals including politicians and celebrities (13%), health organizations (9%), health-related individuals such as clinicians (6%), and news organizations (3%). Content posted by people in or seeking recovery typically aimed to provide emotional support to others, celebrate a sobriety milestone, express gratitude, or acknowledge mutual-help group participation. Sociopolitical commentary—in 15% of posts—advocated for harm reduction strategies and policy change. One in 5 tweets, however, featured marketing content, primarily from addiction treatment industry accounts. Of those, 9 in 10 promoted purported treatments, services, and products (e.g., inpatient treatment centers, sober houses, detox programs, counseling, medications, and self-help books), including approaches not supported by scientific evidence.

The study highlights a critical need to regulate addiction-related marketing practices on social media, researchers concluded. While Twitter was commonly used to provide or receive support around recovery and to advocate for beneficial policies and strategies, the substantive presence of addiction treatment industry content presented a risk to people seeking guidance. Previous research has highlighted ethical issues in the addiction treatment industry’s misrepresentation of its services online, including predatory marketing and fraudulent practices. In combination with the tendency of social networking platforms and search engines to prioritize commercial interests over the risk of harm to users, the nature of addiction industry social marketing could erode trust in treatment, reinforce barriers to evidence-based services, and contribute to poor outcomes.

Content analysis of substance use disorder recovery discourse on Twitter: From personal recovery narratives to marketing of addiction treatment. A. M. Russell, D. Valdez, M. Wang, J.-P. Allem, B. Bergman, J. Kelly, D. M. Litt, P. Massey.

ACER-24-6271.R1

COLUMBUS, Ohio – The combination of prescribed central nervous system stimulants, such as drugs that relieve ADHD symptoms, with prescribed opioid medications is associated with a pattern of escalating opioid intake, a new study has found. 

The analysis of health insurance claims data from almost 3 million U.S. patients investigated prescribed stimulants’ impact on prescription opioid use over 10 years, looking for origins of the so-called “twin epidemic” of combining the two classes of drugs, which can increase the risk for overdose deaths. 

“Combining the two drugs is associated with an increase in overdose deaths. This is something we know. But we didn’t know whether stimulant use has a causal role in high use of opioids, so we conducted a big data analysis of how these two patterns interacted over a long period of time,” said senior study author Ping Zhang, associate professor of computer science and engineering and biomedical informatics at The Ohio State University. 

“What we found is that if someone is taking a stimulant and an opioid at the same time, they’re generally taking a high dose of the opioid,” he said. “And if the patient in this study population takes the stimulant before beginning opioid use, they are more likely to have higher doses of subsequent opioids.” 

The study was published Feb. 17 in The Lancet Regional Health – Americas.     

The research team obtained data on 22 million patients with 96 million opioid prescriptions from MarketScan Commercial Claims and Encounters, a large U.S. health insurance database. Researchers established a cohort for this study of 2.9 million patients with an average age of 44 who had at least two independent opioid prescriptions between 2012 and 2021. 

Because these prescriptions included a range of oral formulas – codeine, hydrocodone, methadone, oxycodone, morphine and others – researchers standardized every prescription to morphine milligram equivalents (MME) and calculated each patient’s monthly intake of opioids. The MME computation from electronic health records was previously co-developed by co-senior author Wenyu Song, an instructor at Harvard Medical School. 

First author Seungyeon Lee, a PhD student in Zhang’s lab, used statistical modeling and classified patients into five baseline groups of opioid dosage trajectory over the 10-year study period: very low-dose, low-dose decreasing, low-dose increasing, moderate-dose increasing and high-dose sustained use. 

“Some patients had stable low-dose opioid use, while others had increasing or high dose patterns over time,” Lee said. 

Of the total cohort, 160,243 patients (5.5%) also were prescribed stimulants. The addition of a monthly calculated cumulative number of stimulant prescriptions to the model and statistical analysis showed a shift in the trajectory groups. Characteristics that could serve as risk factors for increasing opioid use also emerged in the data, Lee said. 

Moderate-dose increasing and high-dose groups had an overall higher average MME and a higher proportion of patients with diagnoses of depression, anxiety and attention-deficit/hyperactivity disorder compared to other groups. The low-dose increasing group also had a higher proportion of patients with ADHD compared to the low-dose decreasing group.

The most common diagnoses linked to co-prescription of stimulants and opioids were depression and ADHD or ADHD and chronic pain. 

“This was an important finding, that many patients with ADHD and depression, also experiencing chronic pain, have an opioid prescription,” said Zhang, also a core faculty member in the Translational Data Analytics Institute at Ohio State. “This cohort represents a very realistic health care problem.” 

Even taking those factors into account, the model showed that stimulant use was key to driving up the odds that patients who took both stimulants and opioids would belong to a group of people who increased their doses of opioids.

“Stimulant use before initiating opioids and stimulant co-prescription with opioids are both positively associated with escalating opioid doses compared to other factors,” Lee said.

Analysis of geographic and gender data also offered some clues to opioid use patterns in the United States. Patients in the South and West regions had higher total opioid intakes over the 10-year study period compared to the Northeast and North Central regions, with the highest frequency of opioid prescriptions in the South and higher MMEs per prescription in the West. Males also had higher average daily opioid intakes than females. 

The results linking high opioid doses and stimulant use suggest stimulants may be a driving force behind the emergence of the twin epidemic and offer evidence that regulation of stimulant prescribing may be needed for patients already taking prescription opioids, the researchers said. In addition to the increased risk of overdose death, co-using prescription stimulants and opioids can increase the risk for cardiovascular events and mental health problems, previous research has shown. 

Zhang’s Artificial Intelligence in Medicine Lab focuses primarily on using AI to aid in clinician decision making, and these findings are part of a larger project aimed at development of safer personalized treatment recommendations for people who are prescribed both opioids and stimulants. 

“We want to reduce the risk of opioid- or stimulant-related adverse drug events in real-world practice,” Zhang said. 

This work was funded by the National Institute of General Medical Sciences, the National Institute on Drug Abuse and the National Science Foundation. 

Additional co-authors were David Bates of Harvard Medical School and Richard Urman, chair of anesthesiology in Ohio State’s College of Medicine.

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Contact: Ping Zhang, [email protected]

Written by Emily Caldwell, [email protected]; 614-292-8152