Addiction and GLP-1: From rats to man

Abstract:
Substance use disorder (SUD) is a devastating disease involving chronic relapse. Indeed, in 2023, alone, well over 100,000 people in the United States lost their lives to drug overdose. With only three medications approved for the treatment of SUD and addiction, new treatments clearly are needed. Here, we will discuss preclinical and clinical trials data that help us to better understand the disease of addiction and its treatment. Specifically, preclinical data show that some individuals are vulnerable, and some resistant, to drug taking. For the vulnerable individuals, supporting data reveal that the SUD does not take weeks or months to develop, but begins to develop with the first exposure to drug. An important insight is made when examining the nature of the behavior of the experimental subjects during the development of this disease. Combined data show that early anticipation of the availability of drug is associated with the onset of an aversive state as reflected by high levels of the stress hormone, corticosterone, low levels of dopamine in the nucleus accumbens, and by the expression of aversive taste reactivity behaviors. Importantly, these same behavioral and physiological responses are associated with the onset of conditioned withdrawal - suggesting that early development of SUD/Addiction (preaddiction, if you will) can be tracked by the development of conditioned withdrawal in vulnerable rats. Withdrawal, of course, can be reduced by treatment with an opioid agonist such as buprenorphine (a medication used for the treatment of opioid use disorder, MOUD), but it also can be reduced by treatment with a glucagon-like peptide-1 receptor agonist (GLP-1RA). GLP-1RAs are known to cause satiety and to regulate glucose in rats and humans and, as such, are approved for the treatment of obesity and type two diabetes mellitus. Importantly, GLP-1RAs also effectively reduce responding for nicotine, cocaine, alcohol and opioids. In our hands, GLP-1RAs reduce heroin and fentanyl seeking elicited by drug-related cues, stress, and by the drug itself in rats, and they reduce opioid craving in humans in residential treatment for OUD. GLP-1RAs, then, can reduce craving, withdrawal, seeking and even taking of drug and, as such, hold promise as a novel treatment for substance use disorder/addiction. This work was supported by UG3 DA050325.

About the Speaker:
Dr. Patricia “Sue” Grigson earned her Bachelors of Science from Elizabethtown College in Psychology, her Master of Science and her Ph.D. from Rutgers University in Biopsychology in the study of reward with Dr. Charles Flaherty, and then completed her postdoctoral training at the Penn State College of Medicine in the study of taste and motivated behavior with Dr. Ralph Norgren. Thereafter, she accepted a tenure-track faculty position at the Penn State College of Medicine, where she is now a tenured professor and Chair of the Department of Neural and Behavioral Sciences and Interim Chair of Pharmacology. Over this time, Dr. Grigson and her students have studied the comparison of natural rewards with addictive substances, individual vulnerabilities to addiction, factors that reduce or accentuate the development of addiction and, along with her colleagues, novel interventions for the treatment of the disease in rats and humans. Dr. Grigson has received 30 years of nearly continuous funding from the National Institutes of Health and via CURE funding from the Pennsylvania Department of Health. She is the recipient of a MERIT Award and currently is MPI of a UG3/UH3 award from the HEALing Initiative to test the safety and efficacy of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of opioid use disorder in animal models and in humans. Among other awards, Dr. Grigson was the recipient of the College of Medicine's Annual Hinkle Society Junior Investigator Award in 2000, and in 2004 she received the Alan N. Epstein Research Award from the Society for the Study of Ingestive Behavior. Dr. Grigson co-founded the Penn State Hershey Commission for Women and she co-founded and is the Director of the Penn State Addiction Center for Translation.

Contact

Nikki Crowley
nzc27@psu.edu