About

Corinde E. Wiers, Ph.D., is an Assistant Professor of Psychiatry at the University of Pennsylvania's Perelman School of Medicine. Her research focuses on cognitive and neurobiological processes involved in substance use disorder (AUD), utilizing PET and MRI neuroimaging techniques. Her lab investigates the effects of metabolic ketosis on brain energetics and alcohol consumption in individuals with AUD, supported by NIH/NIAAA grants. Dr. Wiers has contributed to understanding the neurochemical and metabolic effects of alcohol in the human brain, as well as genetic and neuroimaging correlates of alcohol addiction and impulsivity. Her work aims to elucidate the neurobiological mechanisms underlying substance use disorders and to explore potential therapeutic interventions.

Research topics

• Psychology
• Medicine
• Neuroscience
• Internal medicine
• Psychiatry

Selected publications

• Adiposity and inflammation mediate altered metabolic profiles in individuals with opioid use disorder

  medRxiv · 2026-04-18

  articleOpen accessSenior authorCorresponding

  Abstract Previous studies have linked opioid use to altered metabolic profiles, but findings have been inconsistent and mechanisms remain unclear. One potential mechanism involves increased adiposity, leading to chronic low-grade inflammation that elevates metabolic risk. Here, we examined metabolic profiles in individuals with opioid use disorder (OUD) and matched non-OUD controls, focusing on the sequential mediating roles of BMI and inflammation. Data from individuals with OUD (n=281) and non-OUD (n=246) were drawn from a natural history screening protocol from the National Institute on Alcohol Abuse and Alcoholism intramural program. Groups were matched on age, sex, race, ethnicity, socioeconomic status, and education via propensity score matching. Metabolic measures included BMI, blood glucose, hemoglobin A1c (HbA1c), and lipid profiles, with lipid imbalance indexed by the atherogenic index of plasma (AIP). Inflammatory markers included C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Individuals with OUD had significantly higher BMI (F 1,481 =12.9, p<0.001), HbA1c (F 1,481 =10.5, p=0.001), lower high-density lipoprotein cholesterol (HDL-C; F 1,481 = 46.2, p< 0.001), higher low-density lipoprotein cholesterol (LDL-C; F 1, 481 =11.9, p< 0.001), and higher AIP (F 1,481 =20.7, p< 0.001) compared to non-OUD. Inflammatory markers were also elevated in individuals with OUD, including CRP (F 1,481 =9.4, p=0.002) and ESR (F 1,481 =7.4, p= 0.007), and statistically mediated group differences in AIP and HbA1c, respectively. Our results are consistent with prior evidence of metabolic dysfunctions in individuals with OUD and suggest inflammation as a contributing mechanism. Targeting metabolic health and inflammation may offer new avenues for improving long-term health outcomes in OUD.

  PublisherDOI

• Pharmacokinetic effects of a single dose nutritional ketone ester supplement on brain glucose and ketone metabolism in alcohol use disorder

  Psychiatry Research Neuroimaging · 2026-01-29 · 1 citations

  articleOpen accessSenior author

  Acute alcohol use reduces brain glucose metabolism while increasing uptake of acetate, a byproduct of alcohol. This metabolic shift persists in individuals with alcohol use disorder (AUD) and may offer a treatment target. Recent studies show that ketone therapies can lessen alcohol withdrawal and cravings. In this study, we tested whether a single dose of a ketone ester (KE) supplement affects brain energy use and alcohol craving. Ten participants (five with AUD, five healthy controls) received two FDG-PET brain scans-one after taking 395 mg/kg KE and one at baseline-in a randomized order. Additionally, five AUD participants underwent magnetic resonance spectroscopy to measure cingulate β-hydroxybutyrate (BHB). KE lowered blood glucose and increased BHB in both groups. Brain scans revealed a 17% reduction in glucose metabolism, especially in the frontal, occipital, and cingulate cortices, as well as the hippocampus, amygdala, and insula. No major differences were observed between AUD and control groups. KE significantly reduced alcohol craving in AUD participants and tripled cingulate BHB levels. These findings suggest that a single KE dose can rapidly shift brain energy use from glucose to ketones, and may help reduce cravings in AUD, supporting its potential as a therapeutic approach.

  PublisherDOI

• A ketogenic diet reduces hepatic alcohol metabolism and alcohol consumption in rats

  Neuropsychopharmacology · 2026-03-20

  articleOpen access

  Previous work showed that rats that were exposed to a high-fat, low-carbohydrate/protein ketogenic diet (KD) exhibited elevated blood alcohol levels following alcohol exposure compared with rats fed regular chow. Additionally, the administration of a KD prior to alcohol exposure (i.e., a history of KD) reduced alcohol consumption in alcohol-dependent rats that were no longer on the diet. In the present study, we investigated the mechanisms by which a KD alters alcohol metabolism and tested whether ongoing KD exposure reduces alcohol consumption in rats. We hypothesized that chronic KD exposure alters hepatic alcohol-metabolizing enzymes, slows alcohol metabolism, and reduces alcohol self-administration in alcohol-dependent rats. We found that male and female rats maintained on a KD had higher blood alcohol levels, lower hepatic alcohol dehydrogenase 1 protein levels, and a higher nicotinamide adenine dinucleotide [NAD+]/[NADH] ratio in the liver cytoplasm compared with chow-fed control rats. Furthermore, KD-fed rats demonstrated lower brain glucose uptake relative to chow-fed control rats. In a model of alcohol dependence, the KD reduced alcohol consumption in male, but not female, rats compared with chow-fed rats. These findings suggest that a KD alters brain energetics and alcohol metabolism, which may contribute to reduced alcohol consumption in male rats.

  PublisherDOI

• Emotional arousal of graphic cigarette warning labels loses its beneficial effects on craving reduction after repeated exposure – A longitudinal neuroimaging study

  Drug and Alcohol Dependence · 2026-01-29

  articleOpen accessCorresponding

  Graphic warning labels (GWLs) on cigarette packaging have been implemented in many countries. In the U.S., however, GWLs have faced legal challenges based on concerns that their aversive imagery elicits excessive emotional arousal without sufficient data to support its beneficial impact. This longitudinal study examined how GWLs’ level of arousal affects cigarette craving and neural responses related to emotional processing. A total of 158 adults who smoked cigarettes were exposed to either high-arousal (n=79) or low-arousal (n=79) GWLs attached to their cigarette packs for 4 weeks. Cigarette craving and brain responses to GWLs were measured using functional magnetic resonance imaging before and after the exposure period. The amygdala, a key region involved in emotional processing, was the brain region of interest. At baseline, high-arousal GWLs elicited a greater reduction in craving and stronger amygdala activation than low-arousal GWLs. However, by week 4, the differences in craving reduction and amygdala response between groups were no longer significant. Amygdala activity mediated the effect of GWLs on craving reduction, with the mediation effect being more pronounced in the high-arousal group than the low-arousal group at baseline but not at week 4. The impact of GWL-induced arousal on cigarette craving appears to diminish over time, likely due to habituation in amygdala reactivity. High-arousal GWLs do not provide sustained advantages over low-arousal ones. Low-arousal GWLs may represent a more practical and legally defensible approach to tobacco control in the U.S. • We tested the effects of cigarette GWLs evoking high vs. low emotional arousal. • High-arousal GWLs initially activated amygdala and reduced craving more strongly. • Differences between high- and low-arousal GWLs disappeared after 4-week exposure. • Amygdala habituation may underlie the diminishing effect of arousal over time. • High-arousal imagery in GWLs may not offer long-term benefits.

  PublisherDOI

• Hippocampal volume and brain tau pathology in opioid use disorder: Associations with non-fatal opioid overdose

  Addiction Neuroscience · 2026-01-18 · 1 citations

  articleOpen accessSenior authorCorresponding

  • Individuals with OUD had lower hippocampal volume but no evidence of brain tau deposition, compared to healthy controls. • History of opioid OD did not affect hippocampal volume or brain tau deposition. • Individuals with a history of opioid OD had poorer memory performance than healthy controls. Opioid use disorder (OUD) is associated with high rates of overdose (OD)-related morbidity and mortality. OD can cause hypoxic-ischemic injury to oxygen-sensitive brain regions such as the hippocampus. Post-mortem studies show Alzheimer’s disease-like hyperphosphorylated tau pathology in the brains of individuals with OUD. Neurocognitive impairments in individuals with OUD may reflect incipient dementia and contribute to poor clinical outcomes. Alternatively, OUD and OD could be independent risk factors for Alzheimer’s disease. To date, no study has evaluated the effects of non-fatal ODs or chronic OUD on hippocampal volume and tau deposition in the human brain in vivo . To fill this gap, we examined hippocampal volumes in OUD individuals (n=60) and healthy controls (HC, n=30) using T1-weighted magnetic resonance imaging (MRI). We found lower bilateral hippocampal volumes in OUD patients than HCs (p<0.001), but no differences between OUD individuals with a history of OD and those without (NOD) (p=0.92). We measured brain tau deposition using Positron Emission Tomography (PET) with [ 18 F]PI-2620 in n=4 HC, n=4 OUD-NOD, and n=4 OUD-OD individuals, and found no difference in brain tau between groups. Functional MRI assessment of episodic memory showed no differences in memory performance or hippocampal activity between groups, although OUD-OD individuals had poorer performance than HC with a medium effect size (d=0.56). In summary, we confirm prior findings of smaller hippocampal volumes in participants with OUD than in HC. However, with a limited sample size, our findings do not show evidence of brain tau deposition in OUD participants with or without OD histories.

  PublisherDOI

• Drug Use Severity is Linked to Reduced Brain Network Segregation in Opioid Use Disorder

  Drug and Alcohol Dependence · 2025-02-01

  articleSenior author
  PublisherDOI

• [ ¹¹ C]Carfentanil PET Whole-Body Imaging of μ-Opioid Receptors: A First in-Human Study

  Journal of Nuclear Medicine · 2025-05-08

  article

  μ-opioid receptors (MORs) are G-coupled receptors widely expressed in the brain and body. MORs have a high affinity for both endogenous opioids such as β-endorphins and exogenous opioids such as fentanyl. They mediate pain and reward and have been implicated in the pathophysiology of opioid, cocaine, and other substance use disorders. Using an instrument with a long axial field of view and the MOR-selective radioligand [¹¹C]carfentanil, we measured the whole-body distribution of MORs in 13 healthy humans. We also examined sex differences in MOR distribution at baseline and after pretreatment with the MOR antagonist naloxone. <b>Methods:</b> Six female and 7 male healthy subjects underwent 2 [¹¹C]carfentanil PET imaging sessions—one at baseline and one immediately after pretreatment with the MOR antagonist naloxone (13 μg/kg). Whole-body PET imaging was performed on an instrument with a 142-cm axial bore. [¹¹C]carfentanil brain distribution volume ratios were determined using the occipital cortex and the visual cortex within it as reference regions. For peripheral organ distribution volume ratios, the descending aorta and proximal-extremity muscle (biceps/triceps) were used as reference regions. <b>Results:</b> Naloxone blockade reduced MOR availability by 40%–50% in the caudate, putamen, thalamus, amygdala, and ventral tegmentum, brain regions known to express high levels of MORs. Women showed greater receptor occupancy in the thalamus, amygdala, hippocampus, and frontal and temporal lobes and a greater naloxone-induced reduction in thalamic MOR availability than men (<i>P</i> &lt; 0.05). For determining brain MOR availability, there was less variance in the visual cortex than in the occipital cortex reference region. For peripheral MOR determination, the descending aorta reference region showed less variance than the extremity muscle, but both showed blocking effects of naloxone. <b>Conclusion:</b> [¹¹C]carfentanil whole-body PET scans are useful for understanding MOR physiology under both baseline and blocking conditions. Extra–central nervous system reference regions may be useful for quantifying radiotracers when a region devoid of binding in the central nervous system is unavailable. The long axial field of view was useful for measuring changes in the short-lived radiotracer [¹¹C]carfentanil, with and without naloxone blocking. Further research is needed to evaluate the behavioral and clinical relevance of sex differences in naloxone–MOR interactions.

  PublisherDOI

• Phenome-wide analysis of genetically imputed neuroimaging phenotypes reveals associations with psychiatric traits in a multi-ancestry cohort

  medRxiv · 2025-12-17

  preprintOpen access

  Background: Understanding how variation in brain structure and function contributes to psychiatric and behavioral phenotypes remains a key challenge. The absence of neuroimaging data in many study samples limits this effort. Methods: We used genome-wide association study (GWAS) summary statistics from the UK Biobank to impute 301 brain imaging-derived phenotype (IDP) genetic scores (IGS) in the Yale-Penn cohort, which is enriched for substance use disorders (n = 10,275; 52.8% European-like [EUR] and 47.2% African-like [AFR] genetic ancestry). The brain IDPs include white matter microstructure, regional volume, and resting-state functional connectivity measures, for which we generated IGS in the Yale-Penn participants. We then conducted a brain-wide phenome-wide association study (pheWAS) of the 301 IGS across 692 behavioral, psychiatric, and environmental traits. Results: Among EUR individuals, we identified 19 IGS with significant associations that survived within-trait corrections for multiple testing. These included links between genetically predicted white matter integrity and sedative abuse, tobacco withdrawal, attention deficit hyperactivity disorder (ADHD); structural brain volumes and cocaine dependence, ADHD, and conduct disorder; and functional connectivity with substance-related symptoms and social phobia. Among AFR individuals, we identified 15 IDPs with significant associations, including associations between genetically predicted white matter integrity and stimulant use disorder, regional brain volumes and opioid withdrawal/dependence, and functional connectivity and cocaine craving. Conclusions: Genetically imputed brain features capture biological variation associated with psychiatric traits. This work provides a framework for leveraging genetic data to link neuroimaging measures to substance use and mental health outcomes in samples that lack imaging data.

  PublisherOA PDFDOI

• Mu-opioid receptor availability in patients with opioid use disorder treated with either methadone or buprenorphine

  medRxiv · 2025-10-08

  preprintOpen access

  Abstract Methadone (MET) and buprenorphine (BUP)—mu-opioid receptor (MOR) agonists—are efficacious treatments for opioid use disorder (OUD). Using high-sensitivity, long axial field-of-view PET imaging with [ 11 C]carfentanil, we compared MOR availability in 5 MET and 5 BUP patients and 13 healthy controls (HCs) in five brain regions: ventral tegmentum, thalamus, caudate, putamen, and amygdala. MOR availability differed across groups (F 10,34 =5.6, p&lt;0.001) and was lower in BUP patients than HCs across all brain regions (mean reduction=39.1±15.2%; p&lt;0.001), lower in MET patients than HCs in the ventral tegmentum and amygdala (p’s&lt;0.05), and lower in BUP than MET patients in four of five regions (p’s&lt;0.05). MOR availability was inversely related to serum drug levels, linear for MET (R²=0.83, linear) and logarithmic for BUP (R²=0.96). [ 11 C]carfentanil PET may be useful in guiding personalized OUD treatment based on receptor engagement, which differs significantly between the two opioid agonist treatments. Studies are needed to link MOR availability with specific clinical characteristics (e.g., hedonic capacity, MOR agonist-associated weight gain) and OUD treatment outcomes.

  PublisherOA PDFDOI

• Multiple dimensions approach in polysubstance use: An ESEM analysis based on the RDoC framework

  Psychiatry Research Neuroimaging · 2025-01-29 · 1 citations

  article
  PublisherDOI

Recent grants

• Ketone ester intervention in alcohol use disorder

  NIH · $747k · 2019–2024

Frequent coauthors

• Nora D. Volkow

  National Institute on Drug Abuse

  259 shared

• Gene‐Jack Wang

  National Institute on Alcohol Abuse and Alcoholism

  157 shared

• Dardo Tomasi

  National Institute on Alcohol Abuse and Alcoholism

  103 shared

• Ehsan Shokri‐Kojori

  National Institute on Alcohol Abuse and Alcoholism

  94 shared

• Peter Manza

  83 shared

• Şükrü Barış Demiral

  National Institutes of Health

  46 shared

• Felix Bermpohl

  St. Hedwig-Krankenhaus

  38 shared

• Amna Zehra

  University of Maryland, Baltimore

  36 shared

Education

• PhD, Psychology

  Freie Universität Berlin

  2014