schmidtlab.org

Suraj Neelamagam presented on Upenn neuroscience research symposium

Grace — Tue, 21 Apr 2026 18:39:51 +0000

On April 17th, Suraj Neelamagam presented his senior thesis at the UPenn Neuroscience Research Symposium. Conducted in collaboration with Antonia Caffrey and Riley Merkel under the advisement of Dr. Heath Schmidt, his research explored how GLP-1 receptors in the central amygdala (CeA) can be targeted to reduce cocaine-seeking behavior.
His findings show that the CeA-to-NAc circuit plays a critical role in the behavioral effects of Exendin-4 (Ex-4), suggesting that this pathway is responsible for GLP-1R-mediated attenuation of cocaine reinstatement. The research also found that increased GLP-1R signaling is associated with reduced anxiety-like behaviors.
Suraj will be graduating in May 2026. Congratulations on this incredible milestone!

Tirzepatide on cocaine addiction paper by Christian Edvardsson and Grace Zhang

Grace — Wed, 25 Mar 2026 18:49:46 +0000

Building on their earlier work showing that appetite-regulating peptides reduce alcohol intake via the paraventricular thalamus, the team has turned their attention to cocaine — with striking results. Their new EBioMedicine study finds that tirzepatide, a GIP/GLP-1 receptor agonist approved for diabetes and obesity, dose-dependently reduced cocaine self-administration, motivation, and relapse behaviour in male rodents. It also normalised cocaine-induced dopamine elevations across mesocorticolimbic circuits — consistent with the reward-dampening effects seen in their alcohol research. With no approved pharmacotherapy for cocaine use disorder, the clinical availability of tirzepatide makes these findings particularly timely.

link:https://pubmed.ncbi.nlm.nih.gov/41875498/

Congratulations to Cajsa and Antonia on your Neuropharmacology paper!

Grace — Wed, 11 Mar 2026 19:08:16 +0000

We’ve long known that appetite-regulating peptides play a role in alcohol use disorder — but where in the brain does this happen? Our latest study points to a surprising player: the paraventricular thalamus (PVT).
In our recent paper, we found that activating the amylin receptor (AMYR) in the mid-PVT reduces alcohol intake and blunts alcohol-induced dopamine release in the nucleus accumbens — a key reward circuit. This effect appears to be sex-dependent, observed in males but not females, potentially linked to differences in glutamatergic projections from PVT to NAc. These findings open a new window into the neurobiology of AUD and highlight the mid-PVT as a novel target worth exploring for future treatments.

Link:https://pubmed.ncbi.nlm.nih.gov/41763298/

A Meta-Analysis of New Persistent Opioid Use by Yoonjae Lee and Dr. Schmidt

Grace — Mon, 02 Feb 2026 16:06:03 +0000

One in nine Americans will undergo a surgical procedure during their lifetime; for some, the treatment of postoperative pain represents their first prolonged exposure to an opioid. New persistent opioid use (NPOU)—defined as continued use beyond the typical three-month recovery period in opioid-naïve patients—is linked to increased morbidity, mortality, and opioid-related complications. A comprehensive literature search of 27 articles showed that opioid-naïve individuals insured by Medicaid, or those with preoperative anxiety, depression, or benzodiazepine use, face a higher risk for NPOU. This paper suggests that healthcare providers should pay extra attention to patients with these specific clinical and sociodemographic markers.

Link:https://pubmed.ncbi.nlm.nih.gov/41452764/

Grace Zhang Presents Research on Biased GLP-1 Agonist for Substance Use Disorders

Grace — Tue, 28 Oct 2025 14:18:47 +0000

Grace Zhang presented a poster at the Mid-Atlantic Pharmacology Society 2025 Conference at the Smilow Center for Translational Research at the University of Pennsylvania. Working with collaborators Antonia Caffery and Ricardo Petrilli Fortuna, Zhang investigated Exendin-Phe (Ex-Phe), a biased GLP-1 receptor agonist for treating substance use disorders.

Congratulations Dr. Herman!

Grace — Wed, 17 Sep 2025 21:12:11 +0000

In August, Rae successfully defended her thesis entitled “Behavioral and Circuit-Level Insights into GLP-1 Receptor Agonist-Mediated Reduction of Drug Seeking”. Since joining the lab in 2019, Rae has consistently produced exceptional and impactful work. She has also been an incredible mentor to several undergraduate students, guiding them through meaningful research projects of their own. We have learned so much from Rae’s expertise, dedication, and collaborative spirit. Congratulations, Dr. Herman!

Congratulations Antonia and colleagues on your British Journal of Pharmacology paper!

Grace — Wed, 17 Sep 2025 21:08:31 +0000

On June 2, 2025, Antonia, Enzo, and colleagues published a study in the British Journal of Pharmacology titled ‘A GLP-1R/Y1 receptor/Y2 receptor triple agonist decreases fentanyl-evoked dopamine release in the nucleus accumbens and attenuates fentanyl taking and seeking in rats’. Emerging literature indicates that simultaneously targeting glucagon-like peptide-1 receptors (GLP-1Rs) and neuropeptide Y receptors (Y1/Y2) may represent a new pharmacotherapeutic approach to treating opioid use disorder (OUD). The overall goal of this study was to screen the efficacy of GEP12, a novel GLP-1R/Y1 receptor/Y2 receptor triple agonist, to reduce voluntary fentanyl taking and seeking. GEP12 reduced fentanyl taking in both male and female rats and shifted the fentanyl self-administration dose–response curve downward. Importantly, we identified behaviourally selective doses of GEP12 that were well-tolerated in fentanyl-experienced rats. GEP12 also reduced fentanyl seeking during abstinence in both male and female rats at doses that did not alter food intake or produce adverse malaise-like effects. To identify a central mechanism underlying the efficacy of GLP-1R/Y1 receptor/Y2 receptor triple agonists, we showed that systemic GEP12 penetrated the brain and distributed to the mesolimbic reward system. Using in vivo fibre photometry, we discovered that GEP12 reduced fentanyl self-administration-evoked dopamine release in the nucleus accumbens. Together, these findings support the continued development of GLP-1R/Y1 receptor/Y2 receptor triple agonists as a novel class of pharmacotherapies for treating OUD.

Keywords: dopamine; glucagon‐like peptide‐1; neuropeptide Y; nucleus accumbens; opioid; relapse.
Link to the paper: https://pubmed.ncbi.nlm.nih.gov/40456683/

Congratulations Cajsa and Antonia on your European Neuropsychopharmacology paper!

Grace — Wed, 17 Sep 2025 20:45:18 +0000

On July 10th, researchers from the Jerlhag and Schmidt laboratories published groundbreaking findings in European Neuropsychopharmacology demonstrating that semaglutide—a GLP-1R medication currently used for diabetes and weight management—significantly reduces cocaine-seeking behaviors in laboratory studies. The study, titled “Semaglutide suppresses cocaine taking, seeking, and cocaine-evoked dopamine levels in the nucleus accumbens,” reveals that this long-acting GLP-1 receptor agonist may offer new hope for treating cocaine use disorder (CUD). Using established cocaine self-administration models in male rats, researchers tested various doses of semaglutide and found it effectively reduced voluntary cocaine consumption, decreased motivation to seek cocaine, and prevented relapse-like cocaine-seeking behavior. Importantly, neither of the tessted doses altered kaolin intake, a measurement of malaise, in cocaine-experienced rats. These findings strengthen the evidence for GLP-1 receptors playing a crucial role in addiction mechanisms and provide compelling support for advancing semaglutide to clinical trials as a potential treatment for cocaine use disorder.

Keywords: Cocaine use disorder, GLP-1 receptor, addiction treatment, semaglutide, dopamine, relapse prevention
link to the paper: https://pubmed.ncbi.nlm.nih.gov/40644799/

Congratulations Austin!

Grace — Thu, 03 Jul 2025 18:49:20 +0000

Austin Pothikamjorn has officially graduated from the University of Pennsylvania and is leaving the Schmidt Lab to begin an exciting new chapter. He will be joining the Division of Addiction Psychiatry at Beth Israel Deaconess Medical Center in Boston, MA as a Research Assistant. There, he will be exploring the clinical side of substance use research—focusing on drug policy and clinical trials. We’re incredibly proud of Austin’s accomplishments and can’t wait to see the impact he’ll make in the field of addiction psychiatry. Thank you, Austin, for all your hard work, insight, and positive energy in the lab. Wishing you all the best on this next adventure!

Congratulations, Cajsa, on successfully defending your thesis!

Grace — Fri, 28 Mar 2025 18:36:39 +0000