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UAMS Receives NIH Grant for First Comprehensive Study of ‘Synthetic Marijuana’ Dangers

A team of University of Arkansas for Medical Sciences (UAMS) researchers has received a federal grant to conduct the first comprehensive study of the dangers posed by synthetic marijuana products.

The $2.7 million grant from the National Institutes of Health (NIH) National Institute on Drug Abuse (NIDA) will enable a seven-member interdisciplinary research team to determine the toxicity of the man-made cannabinoids and inform policymakers as they consider regulating the products, which are intended to mimic the effects of marijuana.

“Synthetic cannabinoid products such as K2 and Spice are deceptively marketed as safe and legal alternatives to marijuana, but admissions to emergency rooms and calls to poison control centers suggest that they are certainly not safe,” said Paul Prather, Ph.D., the study’s principal investigator and professor in the UAMS College of Medicine Department of Pharmacology and Toxicology. “Users of these products are experiencing psychosis, seizures, heart attacks and even death.”

Since 2015, there have been 83 calls for synthetic cannabinoid exposures to the Arkansas Poison & Drug Information Center at UAMS. Synthetic cannabinoids are psychoactive chemicals often sprayed on plants that have been cut up to look like natural marijuana. They are also sold as powders, tablets and capsules.

Over the next five years, the UAMS team will explore why the synthetic compounds are more toxic than marijuana, even though both activate the same cannabinoid receptors in the brain. Researchers will study the effects of the man-made compounds on human cells in the lab, in mice, and in those who take synthetic cannabinoids and are admitted to the ER at UAMS and ERs in New York.

“When we test patients who have used synthetic cannabinoids, we can identify what specific compounds are being abused, the levels of compounds and their metabolites in patient samples, and we can link this information to the symptoms that brought them into the ER,” said co-investigator Laura James, M.D., a professor in the UAMS College of Medicine Department of Pediatrics, director of the UAMS Translational Research Institute, and Section Chief, Clinical Pharmacology and Toxicology at Arkansas Children’s Hospital. “The significance of this grant is that numerous experts are working across disciplines to produce findings that will directly improve human health and safety.”

“Our goal is to provide the public and scientific community definitive information that these compounds are not an alternate form of marijuana that’s safe,” Prather said. “This would give federal and state agencies grounds for further regulating these compounds.”

In addition, he said, the team’s findings could help lead to antidotes for people with synthetic cannabinoid toxicity.

The NIH/NIDA grant builds on the work of a one-year 2011 pilot study that was conducted by largely the same team and was funded by the Translational Research Institute. That study, led by James, resulted in development of a clinical test by co-investigator Jeffery H. Moran, Ph.D., to determine the presence and amount of the toxic synthetic compounds in a person’s body. Their findings also informed the work of the Arkansas Legislature, which in 2013 added new synthetic cannabinoid groups to the state’s list of controlled substances (Act 329).

As part of the new five-year study, Moran, assistant professor in the Department of Pharmacology and Toxicology and section director of Environmental Chemistry at the Arkansas Department of Health, will identify the synthetic cannabinoids in blood and urine samples obtained from ER patients.

Co-investigator Anna Radominska-Pandya, Ph.D., will determine what enzymes are metabolizing (inactivating) the synthetic cannabinoids.

“The knowledge gained from this work will help researchers predict whether certain populations are more likely to experience adverse effects from the drugs,” said Radominska-Pandya, a professor in the UAMS College of Medicine Departments of Biochemistry and Molecular Biology and Medicine.

Prather will focus on studying the synthetic compounds and metabolites identified from the urine of the ER patients. By analyzing cells expressing human cannabinoid receptors in his lab he will learn which specific synthetic compounds and metabolites bind to the brain’s cannabinoid receptors as well as other aspects of their activity. For example, he said the man-made compounds bind better to cannabinoid receptors and produce greater activity compared to natural marijuana’s main ingredient – tetrahydrocannabinol (THC). These differences in binding and activity may contribute to the synthetic compounds’ toxicity, but researchers don’t yet know the specific culprits.

“No one has ever looked at this,” Prather said. “To this point it’s just conjecture how these compounds and metabolites bind to and activate cannabinoid receptors.”

Prather’s findings will inform the work of co-investigator William Fantegrossi, Ph.D., who will take the compounds and metabolites that bind to the cannabinoid receptors and study their actions in mice.

“Our animal models should help clarify the toxicity associated with these compounds,” said Fantegrossi, associate professor in the Department of Pharmacology and Toxicology. “Right now when a synthetic cannabinoid user is admitted to the ER, we don’t know what component of the drug really contributed to their symptoms.”

Co-investigator Susan Abdel-Rahman, Pharm.D., professor of pediatrics at the University of Missouri, Kansas City, an expert in pharmacokinetics, will provide consultation to assist Fantegrossi and Moran with their experiments to determine how the synthetic cannabinoids are absorbed, distributed and eliminated in the body.

The research team will be alerted to any surges in synthetic cannabinoid use as well as new cannabinoids that require the team’s study by co-investigator Keith McCain, Pharm.D., associate professor in the UAMS College of Pharmacy and clinical toxicologist in the Arkansas Poison & Drug Information Center, who will be monitoring calls to the UAMS Center.

TRI Welcomes New Advisory Board Members

The Translational Research Institute has expanded its statewide connections with the addition of four Community Advisory Board members. At the board’s June 21 meeting, TRI welcomed:

  • Emma Agnew, Community Services Manager, City of Jonesboro
  • Holli Boyett, Special Projects Coordinator, South Arkansas Migrant Education, Hope
  • Rev. Charles Heam, Springdale Adventist Fellowship 
  • Jim Miles, Administrator, Enroll the Ridge nonprofit, Jonesboro
Meeting on VA campus in North Little Rock, are Community Advisory Board members (front l-r): Charles Moore, Camden; Holli Boyett, Hope; Sarah Facen, Little Rock; Margarita Solorzano, Springdale; Rev. Jerome Turner, Marvell; (back l-r) Anna Huff-Davis, Helena-West Helena; Jim Miles, Jonesboro; Emma Agnew, Jonesboro; Rev. Steve Sullivan, North Little Rock; Rev. Charles Heam, Springdale; and Naomi Cottoms, Helena-West Helena.

Meeting on the VA campus in North Little Rock are Community Advisory Board members (front l-r) Charles Moore, Camden; Holli Boyett, Hope; Sarah Facen, Little Rock; Margarita Solorzano, Springdale; Rev. Jerome Turner, Marvell; (back l-r) Anna Huff-Davis, Helena-West Helena; Jim Miles, Jonesboro; Emma Agnew, Jonesboro; Rev. Steve Sullivan, North Little Rock; Rev. Charles Heam, Springdale; and Naomi Cottoms, Helena-West Helena.

The meeting was hosted at the North Little Rock VA by VA Chaplain Steve Sullivan, a member of the Community Advisory Board. TRI Director Laura James, M.D., provided an overview of the institute’s mission and ongoing projects while learning more about their community work. “I was excited to meet the new members of the Community Advisory Board,” James said. “This is a fantastic group. Each member does meaningful work on behalf of their communities, and they have made time to help us, too. I always feel newly inspired when I see them.”  

UAMS Invites Public to National Discussion on Women’s Heart Health June 30

The public is invited to participate in a June 30 national conversation about women’s heart health hosted by the University of Arkansas for Medical Sciences (UAMS) Translational Research Institute. The event will be live-streamed and is open to anyone who wants to attend in person or join online and via text messaging. 

Called Our Community, Our Health, the discussion will include a panel with UAMS experts in women’s heart health and an Arkansan with a family history of fatal heart disease. The event will begin with a reception a 4:30 p.m. and the town hall will be 5 – 6 p.m. at the UAMS Donald W. Reynolds Institute on Aging, 629 Jack Stephens Drive, Room 1207. For those who prefer to view and participate online, login at http://bit.ly/1YbqKfM. Questions may be submitted via Twitter at #OCOH or #Womenshearthealth.

Rhonda Mattox, M.D. Moderator

Rhonda Mattox, M.D.
Moderator

Conducted in partnership with the University of Florida, the event is designed to engage the public, especially medically underserved communities, in conversations about important health and research topics. One of three women in the United States die each year from cardiovascular diseases and stroke, and an estimated 44 million women in the United States are affected by cardiovascular diseases. 

“Many communities have been left out of the conversation about health research, so we have chosen this unique town-hall format to share information in an unscripted conversation with the public,” said Kate Stewart, M.D., M.P.H., who directs the Translational Research Institute’s Community Engagement Program. 

The conversation will be moderated by Rhonda Mattox, M.D., medical director of the Arkansas Minority Health Coalition.

Meet the Panelists

Jean McSweeney, Ph.D., R.N., who made international headlines in 2003 with her groundbreaking discovery of women’s unique heart attack symptoms. The professor and associate dean for research in the College of Nursing is focused on these symptoms as well as women’s unique risk factors for heart disease. She recently highlighted these risk factors in the American Heart Association’s premier journal, Circulation, and hopes it will raise awareness among women’s doctors so that they may modify their practices to improve health outcomes.

Christina Pettey, Ph.D., R.N., a fellow of the American Heart Association and assistant professor at the UAMS College of Nursing. Her research has focused on examining the causes of cardiovascular health disparities and identifying ways to eliminate them.

Kimberly Moore, of Little Rock, who lost her mother and sister to cardiomyopathy, a chronic disease of the heart muscle. Moore and a brother have also been diagnosed with heart disease. Moore has cardiomyopathy as well as arrhythmogenic right ventricular dysplasia (ARVD). She has a pacemaker and keeps a defibrillator close by.

TRI Makes Plain-Language Consent Templates Available to Clinical Researchers

Plain_LanguageThe Translational Research Institute (TRI), the Center for Health Literacy and the IRB have collaborated to develop Plain-Language Consent Templates on a 5th to 6th grade reading level to improve participants’ comprehension of research procedures. 

Consent forms often have complex sentence structure and use vocabulary that make it difficult for the average adult to understand. Using a Plain-Language Consent can improve a participant’s ability to understand study procedures they are consenting for without compromising the content of the consent.

You can find these Plain-Language Consent Templates on TRI’s website.

UAMS/UTHSC Set ‘Research in Substance Abuse Mini-Symposium,’ June 8 

UAMS and the University of Tennessee Health Science Center (UTHSC) will hold a “Research in Substance Abuse Mini-Symposium,” June 8, 10:30-3:30 p.m., Wilson Education Building, room 115 A/B.

All interested faculty, students and research staff are invited to hear investigators discuss their substance abuse research and discoveries. The symposium seeks to foster communication and collaboration between investigators at both institutions. 

Give Your Grant Application a Competitive Edge

Grant

UAMS investigators, if you want to ensure that your grant application is ready to compete for extramural funding, consider attending a Mock Study Section. These TRI-sponsored sessions are led by experienced faculty researchers with strong track records of external funding.

Reviews are available for laboratory, animal and human subjects projects and may be requested for any external grant application (e.g., NIH, CDC, DOD, USDA, etc.). Both new applications and resubmissions will be considered. Learn more.

Request a Mock Study Section.

TRI offers a range of services to investigators at UAMS, Arkansas Children’s Research Institute and Central Arkansas Veterans Healthcare System, including advice and consultation, biomedical informatics, biostatistics, regulatory matters, and protocol development. Visit our website to learn more about our services: TRI.uams.edu.

Laura James, M.D., Named UAMS Associate Vice Chancellor for Clinical and Translational Research

Laura James, M.D., has been named associate vice chancellor for clinical and translational research at the University of Arkansas for Medical Sciences (UAMS).

James will continue as director of the UAMS Translational Research Institute, a position she has held since 2014, while expanding her role over the institution’s clinical and translational research efforts, said UAMS Chancellor Dan Rahn, M.D.

Laura James, M.D.

Laura James, M.D.

“Translational science is at the heart of our research mission,” Rahn said. “We want to ensure that our researchers have the tools they need to make discoveries and that new knowledge can be applied to improving health and health care as quickly and efficiently as possible. Dr. James is vital to this effort.”

James, as Translational Research Institute director, has overseen development of key services to help researchers achieve their clinical and translational science goals, including:

  • An online researcher-to-researcher networking/collaboration tool called UAMS Profiles
  • An automated services portal for researchers that ensures TRI’s timely assistance with a range of research needs
  • An updated website for researchers, TRI.uams.edu
  • Creation of ARresearch.org, a website and registry for Arkansans who want to participate in research, which will help UAMS researchers more quickly identify research volunteers
  • Creation of a new speaker’s series to education UAMS researchers about opportunities for health sciences innovation and entrepreneurship
  • Decreased by more than 60 percent the time for launching clinical trials that utilize TRI assistance with budget development and negotiations
  • Increased collaboration with other research institutions that are members of the Clinical and Translational Science Award (CTSA) consortium.

James, a professor in the Department of Pediatrics, has a 22-year history of translational research in clinical pharmacology and toxicology at UAMS and Arkansas Children’s Hospital. She has held continuous funding from the National Institute of Diabetes and Digestive and Kidney Diseases since 1999. As a clinician-scientist and founder of the startup company Acetaminophen Toxicity Diagnostics, LLC, she and colleagues developed a rapid diagnostic test for acetaminophen liver injury. In 2014 she was named inaugural fellow of the Arkansas Research Alliance (ARA).

The Translational Research Institute was established with significant UAMS support after receiving a 2009 Clinical and Translational Science Award (CTSA) from the National Institutes of Health (NIH) National Center for Advancing Translational Sciences (NCATS).  The institute’s research services also include biostatistics, biomedical informatics, community engagement, and clinical trials services ranging from budget development and negotiation, regulatory assistance, trial recruitment and research coordination.

James received her medical degree from the University of South Carolina and completed a pediatrics residency at UAMS. She completed fellowships in Pediatric Emergency Medicine and Pediatric Pharmacology and Toxicology at the University of Alabama at Birmingham and UAMS, respectively.

KL2 Alums Gain Traction, Funding for Community-Based Initiatives

Tiffany Haynes, Ph.D., and Keneshia Bryant-Moore, Ph.D.

Tiffany Haynes, Ph.D., and Keneshia Bryant-Moore, Ph.D.

Keneshia Bryant-Moore, Ph.D., F.N.P., R.N., and Tiffany Haynes, Ph.D., began their research careers as KL2 scholars in 2011 and 2012, respectively. Today they are on solid footing as federally funded researchers.

Bryant-Moore, an associate professor in the Fay W. Boozman College of Public Health, is the principal investigator of a $110,000 Patient-Centered Outcomes Research Institute (PCORI) award. The funding complements her $1 million 2014 Health Resources and Services Administration grant supporting her effort to bring together Arkansas faith leaders, educators, researchers and health care providers on June 17 for the second annual Community-Campus Partnership Conference to Address Health Disparities.

“The TRI KL2 scholars program launched my research engagement with the faith community which inspired the theme of this year’s conference,” Bryant said. She noted the assistance of Kate Stewart, M.D., M.P.H., and Camille Hart, M.P.H., from TRI’s Community Engagement program. Her collaborators also include Haynes and KL2 alum Brooke Montgomery, Ph.D.

“I am truly grateful for TRI’s support,” she said.

Haynes, an assistant professor in the College of Public Health, was recently awarded $2.1 million for a faith-based mental health intervention in the Delta. Haynes is co-principal investigator with Karen Yeary, Ph.D. Bryant-Moore is a co-investigator, and two other KL2 alums – Dennis Kuo, M.D., M.P.H., and Elvin Price, Pharm.D., Ph.D., are on the project’s steering committee. The five-year NIH grant will allow the team to test the intervention’s effectiveness as well as strategies for sustaining the intervention.

Haynes, a clinical psychologist, said the intervention is led by lay people, helping improve mental well-being through preventive approaches. Anyone experiencing depression or other mental illness will be guided to a mental health professional.

In addition to two years of KL2 support, Haynes said she was aided by TRI’s research forums.

“This intervention can improve the lives of many underserved people, and it wouldn’t have been possible without the support of TRI,” Haynes said.