About

Reagan R. Wetherill, Ph.D., is an Adjunct Associate Professor of Psychiatry at the University of Pennsylvania's Perelman School of Medicine. Her translational research program is focused on improving treatment outcomes for addictive disorders through neuroscience and clinical neuroimaging techniques. Her work involves identifying individual differences in brain and behavioral vulnerabilities for developing and maintaining addictive disorders, evaluating brain changes following chronic substance use, and understanding mechanisms of treatment effect. Her research spans various populations, including adolescents, adults, youth at risk, and individuals with tobacco, alcohol, cannabis, and opioid use disorders, as well as those with HIV. Dr. Wetherill is recognized as an expert in alcohol-induced memory impairments, specifically alcohol-induced blackouts, and serves as an expert consultant and witness for the Penn Title IX office and in military and civilian courts.

Research topics

• Psychology
• Medicine
• Neuroscience
• Clinical psychology
• Developmental psychology

Selected publications

• Effects of Menstrual Cycle Phase on the Neural Correlates of Electronic Cigarette Versus Tobacco Use

  Drug and Alcohol Dependence · 2025-02-01

  articleSenior author
  PublisherDOI

• “ARRESTED DEVELOPMENT”? COCAINE PATIENTS WITH GENETICS LINKED TO OVER-RESPONSE OF THE STRESS (CORTISOL) SYSTEM SHOW AN “IMMATURE” PATTERN OF POSITIVE, RATHER THAN INVERSE, AMYGDALA RESTING FUNCTIONAL CONNECTIVITY WITH THE VMPFC

  Drug and Alcohol Dependence · 2024-07-01

  article
  PublisherDOI

• Identifying neurofunctional domains across substance use disorders

  The American Journal of Drug and Alcohol Abuse · 2024-07-03

  article

  The domains identified, particularly executive function, were parallel to those observed previously. These factors underscore the heterogeneous nature of SUDs and may be useful in developing more targeted clinical interventions.

  PublisherDOI

• Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity

  JAMA Psychiatry · 2024-02-07 · 36 citations

  reviewOpen access

  Importance: In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. Objective: To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. Evidence Review: The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. Findings: There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. Conclusions and Relevance: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.

  PublisherOA PDFDOI

• Molecular Imaging of Pulmonary Inflammation in Users of Electronic and Combustible Cigarettes: A Pilot Study

  Journal of Nuclear Medicine · 2023-01-19 · 22 citations

  articleOpen access1st authorCorresponding

  Electronic cigarette (EC) use has increased dramatically, particularly among adolescents and young adults, which, like cigarette use, can cause pulmonary inflammation and increase the risk of lung disease. <b>Methods:</b> This preliminary study used positron emission tomography with ¹⁸F-6-(1/2)(2-fluoro-propyl)-4-methylpyridin-2-amine (¹⁸F-NOS) to quantify inducible nitric oxide synthase (iNOS) expression to characterize oxidative stress and inflammation in the lungs in vivo in three age- and sex-matched groups: (1) 5 EC users, (2) 5 cigarette smokers, and (3) 5 never smoke/vape controls. <b>Results:</b> EC users showed greater ¹⁸F-NOS non-displaceable binding potential (BPND) than cigarette smokers (<i>P</i> = 0.03) and never smoke/vape controls (<i>P</i> = 0.01); whereas BPND in cigarette smokers did not differ from controls (p&gt; 0.1). ¹⁸F-NOS lung tissue delivery and iNOS distribution volume did not significantly differ between groups. Although there were no group differences in peripheral inflammatory biomarker concentrations, ¹⁸F-NOS BPND correlated with the pro-inflammatory cytokine tumor necrosis factor-α concentrations (rs= 0.87, <i>P</i> = 0.05) in EC users. Additionally, when EC users and cigarette smokers were pooled together, vaping episodes/cigarettes per day correlated with interleukin-6 levels (rs= 0.86, <i>P</i> = 0.006). <b>Conclusion:</b> This is the first PET imaging study to compare lung inflammation between EC and cigarette users in vivo. We found preliminary evidence EC users had greater pulmonary inflammation than cigarette smokers and never smoke/vape controls, with a positive association between pulmonary and peripheral measures of inflammation.

  PublisherOA PDFDOI

• Social Determinants of Health Associated with How Cannabis is Obtained and Used in Patients with Cancer Receiving Care at a Cancer Treatment Center in Pennsylvania

  Cannabis · 2023-01-01 · 7 citations

  articleOpen access

  Despite increased rates of cannabis use among patients with cancer, there are gaps in our understanding of barriers to accessing cannabis. Social determinants of health (SDoH) are associated with access to healthcare, but few studies have evaluated how SDoH relate to cannabis access and use among cancer patients. We examined whether access to and modes of cannabis use differed across indicators of SDoH among patients receiving treatment from a large National Cancer Institute (NCI) designated cancer center. This anonymous cross-sectional survey was developed in collaboration with the NCI Cannabis Supplement consortium, which funded 12 supplements to NCI Center Core Grants across the United States. We evaluated the association of race, gender, income, and age with mode of cannabis use, source of obtaining cannabis, what influences their purchase, and medical cannabis certification status. Overall, 1,053 patients receiving treatment for cancer in Pennsylvania completed the survey and 352 (33.4%) reported using cannabis since their cancer diagnosis. Patients who identified as Black/African-American were less likely to have medical cannabis certifications (p=0.04). Males and Black/African-Americans were more likely to report smoking cannabis (vs other forms, ps&lt;0.01) and to purchase cannabis from an unlicensed dealer/seller (p&lt;0.01). Lower-income patients were more likely to be influenced by price and ease of access (ps&lt;0.05). Although cannabis users were younger than non-users, age was not associated with any outcomes. The current data shed light on how critical drivers of health disparities (such as race, gender, and income) are associated with where patients with cancer obtain cannabis, what forms they use, and what may influence their purchase decisions.

  PublisherOA PDFDOI

• Reply: Molecular Imaging of Pulmonary Inflammation: Claiming That Vaping Is More Harmful Than Smoking Is Unsupported

  Journal of Nuclear Medicine · 2023-05-11

  letterOpen access1st authorCorresponding

  REPLY: We thank Drs. Polosa, Spicuzza, and Palmucci for their interest and comments on our study. The team’s comments highlight evidence supporting traditional combustible cigarettes as a proinflammatory phenotype and the potential of electronic cigarettes for harm reduction as a tool for smoking

  PublisherOA PDFDOI

• Reward and inhibition in obesity and cigarette smoking: Neurobiological overlaps and clinical implications

  Physiology & Behavior · 2022-12-05 · 18 citations

  reviewOpen accessSenior author
  PublisherOA PDFDOI

• Positron Emission Tomography of Neuroimmune Responses in Humans: Insights and Intricacies

  Seminars in Nuclear Medicine · 2022-10-19 · 14 citations

  reviewOpen access
  PublisherOA PDFDOI

• Using ¹⁸ F-NOS PET Imaging to Measure Pulmonary Inflammation in Electronic and Combustible Cigarette Users: A Pilot Study

  medRxiv · 2022-06-16 · 1 citations

  preprintOpen access1st authorCorresponding

  Abstract Electronic cigarette (EC) use has increased dramatically, particularly among adolescents and young adults, which, like cigarette use, can cause inflammation of the lungs and increase the risk of lung disease. Methods In this preliminary study, we used positron emission tomography with 18 F-6-(1/2)(2-fluoro-propyl)-4-methylpyridin-2-amine ( 18 F-NOS) to quantify inflammation of the lungs in vivo in three age- and sex-matched groups: (1) 5 daily EC users, (2) 5 daily cigarette smokers, and (3) 5 never smoke/vape controls. Results EC users showed greater 18 F-NOS non-displaceable binding potential (BP ND ) than cigarette smokers ( p = 0.03) and never smoke/vape controls ( p = 0.01); whereas BP ND in cigarette smokers did not differ from controls (p &gt; 0.1). 18 F-NOS lung tissue delivery (K 1 ) and iNOS distribution volume (V T ) did not significantly differ between groups. Although there were no group differences in the concentration of the peripheral inflammatory markers TNF-α, IL-6 or IL-8, 18 F-NOS BP ND significantly correlated with the proinflammatory cytokine TNF-α ( r = 0.87, p = 0.05) in EC users. Additionally, when EC users and cigarette smokers were pooled together, vaping episodes/cigarettes per day correlated with IL-6 levels ( r = 0.86, p = 0.006). Conclusion To our knowledge, this is the first PET imaging study to compare lung inflammation between EC and cigarette users in vivo . We found preliminary evidence EC users had greater pulmonary inflammation than cigarette smokers and never smoke/vape controls, with a positive association between pulmonary and peripheral measures of inflammation.

  PublisherOA PDFDOI

Recent grants

• Influence of the natural hormonal milieu on perfusion fMRI smoking cue responses

  NIH · $2.4M · 2016–2022

• NIH Grant K23AA023894

  NIH · $856k · 2021

Frequent coauthors

• Teresa R. Franklin

  53 shared

• Kanchana Jagannathan

  43 shared

• Anna Rose Childress

  California University of Pennsylvania

  38 shared

• Henry R. Kranzler

  Washington University in St. Louis

  22 shared

• Charles P. O’Brien

  22 shared

• Nathan Hager

  Old Dominion University

  21 shared

• Jesse J. Suh

  21 shared

• Michael J. Gawrysiak

  West Chester University

  17 shared