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Sex Differences Affect Efficacy of Opioid Overdose Treatment

Reston, VA (July 24, 2025)—Naloxone (also known as Narcan, the commonly used drug to treat narcotic overdoses) has greater binding to opioid receptors in women’s brains than in men’s brains, according to new research published in the July issue of The Journal of Nuclear Medicine. The first-in-human whole-body PET study suggests men and women may respond differently to opioid use disorder treatments and offers new insights to advance neuropharmacology. 

Opioid misuse is a worldwide epidemic associated with high overdose and mortality rates. The μ-opioid receptor (MOR) is the target of opioid drugs including fentanyl and heroin, as well as well as naloxone, an opioid antagonist used to treat opioid use disorder. MORs are widely expressed in the central nervous system, peripheral organs, and immune system, making them especially useful for assessing functional changes in people with opioid use disorder.

“A better understanding of the interactions of opioid drugs with the MOR could help to elucidate the etiology, prevention, and treatment of opioid use disorder,” said Jacob Dubroff, MD, PhD, associate professor of radiology in the Division of Nuclear Medicine Imaging & Therapy at Perelman School of Medicine at the University of Pennsylvania in Philadelphia. “Using whole-body PET, we investigated MOR physiology in men and women before and after pretreatment with naloxone.”

Six female and seven male healthy subjects underwent two ¹¹C-carfentanil whole-body PET imaging sessions—one at baseline and one immediately after pretreatment with the MOR antagonist naloxone. ¹¹C-carfentanil brain distribution volume ratios were determined using the occipital cortex and the visual cortex within it as reference regions. Peripheral organ distribution volume ratios were also measured using the descending aorta and biceps/triceps as reference regions.

On the whole, naloxone reduced MOR availability by 40–50 percent in brain regions known to express high levels of MORs; a greater reduction was seen in women compared to men. For peripheral MOR distribution, the descending aorta reference region showed less variance than the extremity muscle, but both showed blocking effects of naloxone.

Visual Abstract. Whole-body [11C] carfentanil PET imaging at baseline (left side of panel) and then following naloxone (middle panel) shows μ-opioid receptor (MOR) in the brain (color) and throughout the body.  Weight based naloxone administration results in greater MOR occupancy in women than men (top right blue/red figure showing differences in the thalamus, a brain structure rich in MOR expression).  Whole-body imaging imaging permits dynamic measurements in multiple regions, e.g. aorta, skeletal muscle, that could serve as reference regions. Figure by Chia-Ju Hsieh.

The authors of “[11C]Carfentanil PET Whole-Body Imaging of μ-Opioid Receptors: A First in-Human Study” include Jacob G. Dubroff, Chia-Ju Hsieh, Hsiaoju Lee, Alexander Schmitz, Elizabeth J. Li, Erin K. Schubert, and Robert Mach, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Corinde E. Wiers, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and Henry R. Kranzler, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, and Mental Illness Research, Education and Clinical Center, Crescenz VAMC, Philadelphia, Pennsylvania.

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Please visit the SNMMI Media Centerfor more information about molecular imaging and precision imaging. To schedule an interview with the researchers, please contact Rebecca Maxey at (703) 652-6772 or [email protected].

About JNM and the Society of Nuclear Medicine and Molecular Imaging

The Journal of Nuclear Medicine (JNM) is the world’s leading nuclear medicine, molecular imaging and theranostics journal, accessed 15 million times each year by practitioners around the globe, providing them with the information they need to advance this rapidly expanding field. Current and past issues of The Journal of Nuclear Medicine can be found online at http://jnm.snmjournals.org.

JNM is published by the Society of Nuclear Medicine and Molecular Imaging (SNMMI), an international scientific and medical organization dedicated to advancing nuclear medicine, molecular imaging, and theranostics—precision medicine that allows diagnosis and treatment to be tailored to individual patients in order to achieve the best possible outcomes. For more information, visit www.snmmi.org.