About

Zhenhao Shi, PhD, is a Research Assistant Professor of Psychiatry at the University of Pennsylvania's Perelman School of Medicine. His research expertise encompasses brain imaging, public health, social neuroscience, translational neuroscience, computational psychiatry, substance use disorder, tobacco control, health communication, and cross-cultural psychology. Dr. Shi's work involves investigating neural mechanisms underlying addiction and substance use behaviors, utilizing neuroimaging techniques to explore brain network connectivity and emotional responses related to drug use and prevention. His contributions include studying the effects of graphic warning labels on smoking behavior, neural predictors of vaping, and the pharmacokinetics of nutritional supplements in alcohol use disorder, among other topics.

Research topics

• Psychology
• Medicine
• Neuroscience
• Cognitive psychology
• Psychiatry

Selected publications

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

  medRxiv · 2026-04-18

  articleOpen access

  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

• MEDIAL PREFRONTAL NEUROPLASTICITY DURING EXTENDED-RELEASE NALTREXONE TREATMENT OF OPIOID USE DISORDER – A LONGITUDINAL STRUCTURAL MAGNETIC RESONANCE IMAGING STUDY

  The International Journal of Neuropsychopharmacology · 2025-02-01

  articleOpen access1st authorCorresponding

  Abstract Background Opioid use disorder (OUD) has been linked to macroscopic structural alterations in the brain [1]. The monthly injectable, extended-release formulation of μ-opioid antagonist naltrexone (XR-NTX) is highly effective in reducing opioid craving and preventing opioid relapse [2,3]. Aims & Objectives We aimed to investigate the neuroanatomical effects of XR-NTX by examining the changes in cortical thickness during treatment for OUD. Method Forty-seven OUD patients underwent structural magnetic resonance imaging (sMRI) and were assessed for opioid craving on two sessions: less than 1 day before the first XR-NTX injection (i.e., pre- treatment session); and an average of 11 days after the first injection (i.e., on-treatment session). A sample of fifty-six non-OUD individuals who completed a single imaging session served as a comparison group. sMRI images were analyzed using the volume-based cortical thickness pipeline implemented in the Advanced Normalization Tools. A publicly available [11C]Carfentanil positron emission tomography (PET) dataset was used to assess the relationship between cortical thickness change and mu-opioid receptor (MOR) binding potential across brain regions. Results The thickness of the medial prefrontal and anterior cingulate cortices (mPFC/aCC) was comparable between the non-OUD individuals and the OUD patients at pre-treatment, but showed a significant reduction among the OUD patients from pre-treatment to on-treatment (whole-brain familywise error-corrected p<0.05) (see Figure 1A &1B). Patients with greater reduction in mPFC/aCC thickness also showed greater reduction in opioid craving from pre-treatment to on-treatment (R2=0.19, p=0.002) (see Figure 1C). Analysis with the [11C]Carfentanil PET data indicated that, across brain regions, there was a positive association between MOR binding potential and cortical thickness reduction in regions with relatively high MOR binding potential (R2=0.29, p<0.001) (see Figure 1D). Discussion & Conclusion XR-NTX treatment for OUD is associated with reduced cortical thickness in the mPFC and aCC regions. The reduction does not appear to indicate a restoration to the non-OUD level but rather reflects XR-NTX’ s distinct therapeutic impact on an MOR-rich brain structure. Our findings highlight the neuroplastic effects of XR-NTX that may inform the development of novel OUD interventions. References [1]Shi Z, Li X, Byanyima JI, O’ Brien CP, Childress AR, Lynch KG, et al. Effects of current smoking severity on brain gray matter volume in opioid use disorder– a voxel-based morphometry study. American Journal of Drug and Alcohol Abuse. 2023;49(2):180-9. [2]Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL. Injectable extended- release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial. Lancet. 2011;377(9776):1506-13. [3]Shi Z, Wang A-L, Jagannathan K, Fairchild VP, O’ Brien CP, Childress AR, et al. Effects of extended- release naltrexone on the brain response to drug-related stimuli in patients with opioid use disorder. Journal of Psychiatry and Neuroscience. 2018;43(4):254-61.

  PublisherOA PDFDOI

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

  Drug and Alcohol Dependence · 2025-02-01

  article
  PublisherDOI

• Neural Predictors of Vaping: Covert Emotional Engagement Versus Reactance to Overt Emotional Appeals in Vaping Prevention Message Processing

  American Journal of Preventive Medicine · 2025-12-01 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• Brain Network Segregation is Associated with Drug Use Severity in Individuals with Opioid Use Disorder

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-04 · 1 citations

  preprintOpen accessSenior author

  Opioid use disorder (OUD) is associated with altered brain network connectivity, particularly in the fronto-parietal (FPN), default mode, and salience (SN) networks. At rest, brain networks that are distinct from each other but are partially connected can optimize neural efficiency and support cognitive performance. Previous research found lower network segregation in people with cognitive impairment, alcohol use disorder, and as people age. Here, we examined brain network segregation (a graph theory-based metric of the network integration/segregation balance) in individuals with OUD and hypothesized that recent drug use severity would be linked to reduced network segregation. Forty adults with OUD completed resting-state functional magnetic resonance imaging, the drug use severity subscale of the Addiction Severity Index, and measures of cognition (IQ and working memory), mood, and affect. We grouped 264 brain regions into 10 networks, categorized as association (higher-order cognition) or sensorimotor (sensory and motor) networks. Regression analyses showed that drug use severity predicted lower brain network segregation in the association networks, with the FPN and SN driving this effect. Age predicted lower brain network segregation in the sensorimotor networks, while an interaction with age showed that drug use severity only predicted lower sensorimotor network segregation in younger adults. Cognition did not relate to brain network segregation, but positive affect related to greater SN segregation. Brain network segregation remained stable across OUD treatment. These findings elucidate alterations in brain network segregation related to drug use severity in people with OUD, which may contribute to cognitive impairment and accelerated brain aging.

  PublisherOA PDFDOI

• Self-regulating neohesperidin/silk fibroin composite aerogel for enhanced wound healing via pH-responsive release

  Materials Today Bio · 2025-12-07 · 1 citations

  articleOpen access

  . Collectively, this study establishes a bioactive delivery system with pH-tunable release, anti-inflammatory, antioxidant, and tissue-regenerative capabilities and provides new insights into the application of lignocellulosic materials in wound care, holding great potential for clinical translation.

  PublisherDOI

• Delayed Effects of Cigarette Graphic Warning Labels on Smoking Behavior

  American Journal of Health Promotion · 2025-07-16 · 1 citations

  articleOpen access1st authorCorresponding

  Purpose Graphic warning labels (GWLs) are widely employed to communicate smoking-related health risks. Most GWLs elicit a high level of emotional reaction (ER). Our recent study showed poorer efficacy of high-ER GWLs vs low-ER ones during a month-long naturalistic exposure. Here, we aimed to examine whether GWL effects persist after discontinuing the exposure. Design A secondary analysis investigated the delayed GWL effects on smoking severity. Setting Philadelphia Metropolitan Area, United States. Subjects 96 adult smokers who completed a month-long exposure to high-ER or low-ER GWLs. Measures The number of cigarettes smoked per day (CPD) was measured immediately and 4 weeks after the end of GWL exposure. Participants also indicated their subjective feeling of being relieved from having to see the GWLs. Analysis Generalized estimating equations examined the change in CPD across time and its association with sense of relief. Results We found a significant reduction in CPD from the immediate to the 4-week post-exposure timepoint (11.69 vs 10.30, P = 0.001). There was no difference between the high-ER and low-ER groups in CPD reduction ( P = 0.74). Higher sense of relief was associated with greater CPD reduction in the high-ER group (z = −2.14, P = 0.033). Conclusion Our study suggests lasting impact of GWLs on smoking behavior. The findings may be particularly important to high-ER GWLs, which appear less effective in reducing smoking during active exposure.

  PublisherDOI

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

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

  article
  PublisherDOI

• Long-acting naltrexone restores network connectivity in subjects with co-morbid cannabis and opioid use disorder

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-19

  preprintOpen accessSenior authorCorresponding

  Comorbid substance use disorders (SUDs) are common but difficult to study due to the complex, interacting and overlapping mechanisms through which they affect brain networks. Many datasets collected to investigate a specific SUD include participants with comorbid SUDs. Although most studies treat comorbid SUDs as covariates of no interest, these covariates also contain untapped information. This is particularly relevant as cannabis use disorder (CanUD) has become increasingly prevalent and comorbid with other SUDs that have been more thoroughly studied. While pharmacotherapies have been established for multiple SUDs, none have been approved for CanUD, although naltrexone (NTX) has been associated with reduced use. Here, we conducted a retrospective secondary analysis of functional magnetic resonance imaging (fMRI) data from individuals with primary opioid use disorder (OUD-only, N = 25 pre-NTX, N = 20 on-NTX) with comorbid CanUD (N = 10), alcohol use disorder (AUD, N = 6) or cocaine use disorder (CocUD, N = 7). All participants underwent imaging prior to receiving a therapeutic dose of long-acting intramuscular NTX (Vivitrol), an approved treatment for OUD and AUD but not for CocUD, and again 2 weeks postadministration. At baseline, OUD individuals with comorbid CanUD, AUD or CocUD exhibited distinct functional connectivity (FC) alterations compared to those with OUD-only. These differences were greater in younger participants and primarily involved the default mode network. Following NTX administration, FC differences between the comorbid CanUD and OUD-only groups globally diminished. A similar FC response to NTX was observed in the comorbid AUD group, whereas little change in FC was observed in comorbid CocUD. These findings, combined with prior evidence that NTX reduces cannabis use by dampening reward, suggest NTX may hold promise as a treatment for CanUD.

  PublisherOA PDFDOI

• Brain network segregation is associated with drug use severity in individuals with opioid use disorder

  Drug and Alcohol Dependence · 2025-09-04

  articleOpen accessSenior author
  PublisherOA PDFDOI

Recent grants

• Multivariate Modeling of the Neural Mechanisms of Treatment Response in Opioid Addiction

  NIH · $916k · 2021–2026

Frequent coauthors

• Shihui Han

  Peking University

  39 shared

• Daniel D. Langleben

  University of Pennsylvania

  31 shared

• Corinde E. Wiers

  University of Pennsylvania

  20 shared

• Xinyi Li

  University of Cambridge

  17 shared

• Anna Rose Childress

  California University of Pennsylvania

  13 shared

• Yina Ma

  Chinese Institute for Brain Research

  13 shared

• Yi Rao

  11 shared

• Bingfeng Li

  PowerChina (China)

  11 shared

Labs

• Zhenhao Shi LaboratoryPI

Education

• PhD, Department of Psychology

  Peking University

  2014

• BS, Department of Psychiatry

  Peking University

  2009