Treatment of opioid overdose: current approaches and recent advances

Britch, Stevie C.; Walsh, Sharon L.

doi:10.1007/s00213-022-06125-5

Cited by 96Opioid Use Disorder TreatmentPoisoning and overdose treatmentsSubstance Abuse Treatment and Outcomes

Treatment of opioid overdose: current approaches and recent advances

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Britch, Stevie C., Walsh, Sharon L.·2022·Psychopharmacology

DOI 10.1007/s00213-022-06125-5PMC PMC8986509

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Abstract

Background The USA has recently entered the third decade of the opioid epidemic. Opioid overdose deaths reached a new record of over 74,000 in a 12-month period ending April 2021. Naloxone is the primary opioid overdose reversal agent, but concern has been raised that naloxone is not efficacious against the pervasive illicit high potency opioids (i.e., fentanyl and fentanyl analogs).Methods This narrative review provides a brief overview of naloxone, including its history and pharmacology, and the evidence regarding naloxone efficacy against fentanyl and fentanyl analogs. We also highlight current advances in overdose treatments and technologies that have been tested in humans.Results and conclusions The argument that naloxone is not efficacious against fentanyl and fentanyl analogs rests on case studies, retrospective analyses of community outbreaks, pharmacokinetics, and pharmacodynamics. No well-controlled studies have been conducted to test this argument, and the current literature provides limited evidence to suggest that naloxone is ineffective against fentanyl or fentanyl analog overdose. Rather a central concern for treating fentanyl/fentanyl analog overdose is the rapidity of overdose onset and the narrow window for treatment. It is also difficult to determine if other non-opioid substances are contributing to a drug overdose, for which naloxone is not an effective treatment. Alternative pharmacological approaches that are currently being studied in humans include other opioid receptor antagonists (e.g., nalmefene), respiratory stimulants, and buprenorphine. None of these approaches target polysubstance overdose and only one novel approach (a wearable naloxone delivery device) would address the narrow treatment window.

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Higher naloxone dosing may be required for opioid overdose
Bardsley, R. (2019) · American Journal of Health-System Pharmacy · doi:10.1093/ajhp/zxz208 · Cited by 27 · see citing works
A case of heroin overdose reversed by sublingually administered buprenorphine/naloxone (Suboxone®)
Welsh, C., Sherman, S. G., & Tobin, K. E. (2008) · Addiction · doi:10.1111/j.1360-0443.2008.02244.x · Cited by 25 · see citing works
Antagonization of fentanyl-induced muscular rigidity by denervation of the coerulospinal noradrenergic pathway in the rat
Lui, P.-W., Chang, G., Lee, T., & Chan, S. H. H. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90723-x · Cited by 23 · see citing works
Effective Use of Naloxone by Law Enforcement in Response to Multiple Opioid Overdoses
Kitch, B. B., & Portela, R. C. (2016) · Prehospital Emergency Care · doi:10.3109/10903127.2015.1076097 · Cited by 21 · see citing works
Prepacked naloxone administration for suspected opioid overdose in the era of illicitly manufactured fentanyl: a retrospective study of regional poison center data
Mahonski, S. G., Leonard, J. B., Gatz, J. D., Seung, H., Haas, E. E., & Kim, H. (2019) · Clinical Toxicology · doi:10.1080/15563650.2019.1615622 · Cited by 21 · see citing works
Ventricular Tachycardia After Naloxone Administration: a Drug Related Complication? Case Report and Literature Review
Lameijer, H., Azizi, N., Ligtenberg, J. J. M., & ter Maaten, J. C. (2014) · Drug Safety - Case Reports · doi:10.1007/s40800-014-0002-0 · Cited by 20 · see citing works
4-AMINOPYRIDINE REVERSAL OF FENTANYL-INDUCED RESPIRATORY DEPRESSION IN NORMOCAPNIC AND HYPERCAPNIC PATIENTS
Sia, R. L., & Zandstra, D. F. (1981) · British Journal of Anaesthesia · doi:10.1093/bja/53.4.373 · Cited by 19 · see citing works
Naloxone Use Among Emergency Department Patients with Opioid Overdose
Marco, C. A., Trautman, W. J., Cook, A., Mann, D., Rasp, J., Perkins, O., & Ballester, M. (2018) · Journal of Emergency Medicine · doi:10.1016/j.jemermed.2018.04.022 · Cited by 19 · see citing works
Intravenous use of illicit buprenorphine/naloxone to reverse an acute heroin overdose
Yokell, S. M. A., Zaller, N. D., Green, T. C., McKenzie, M., & Rich, J. D. (2012) · Journal of Opioid Management · doi:10.5055/jom.2012.0098 · Cited by 18 · see citing works
Comparing rates and characteristics of ambulance attendances related to extramedical use of pharmaceutical opioids in Victoria, Australia from 2013 to 2018
Nielsen, S., Crossin, R., Middleton, M., Lam, T., Wilson, J., Scott, D. A., Martin, C., Smith, K. L., & Lubman, D. I. (2019) · Addiction · doi:10.1111/add.14896 · Cited by 18 · see citing works
Reversal of overdose on fentanyl being illicitly sold as heroin with naloxone nasal spray: A case report
Fareed, A., Buchanan‐Cummings, A. M., Crampton, K., Grant, A., & Drexler, K. P. G. (2015) · American Journal on Addictions · doi:10.1111/ajad.12230 · Cited by 17 · see citing works
Ventricular tachycardia following naloxone administration in an illicit drug misuse
Hunter, R. P. (2005) · Journal of Clinical Forensic Medicine · doi:10.1016/j.jcfm.2005.01.011 · Cited by 17 · see citing works
RAPID HIGH DOSE FENTANYL INDUCTION FOR CABG
Kentor, M. L., Schwalb, A. J., & Lieberman, R. W. (1980) · Anesthesiology · doi:10.1097/00000542-198009001-00095 · Cited by 17 · see citing works
Naloxone-induced pulmonary edema: A potential cause of postoperative morbidity in laparoscopic donor nephrectomy
Tripathi, M., Pandey, C., Rao, B., & Nath, S. (2009) · Indian Journal of Medical Sciences · doi:10.4103/0019-5359.49240 · Cited by 16 · see citing works
Harms associated with taking nalmefene for substance use and impulse control disorders: A systematic review and meta-analysis of randomised controlled trials
Johansen, K. G. V., Tarp, S., Astrup, A. V., Lund, H., Pagsberg, A. K., & Christensen, R. (2017) · PLoS ONE · doi:10.1371/journal.pone.0183821 · Cited by 16 · see citing works
Intravenous Buprenorphine: A Substitute for Naloxone in Methadone-Overdosed Patients?
Zamani, N., & Hassanian‐Moghaddam, H. (2017) · Annals of Emergency Medicine · doi:10.1016/j.annemergmed.2016.12.024 · Cited by 15 · see citing works
Doxapram‐mediated Increase in Cardiac Output Reduces Opioid Plasma Concentrations: A Pharmacokinetic/Pharmacodynamic–Pharmacokinetic/Pharmacodynamic Modeling Study in Healthy Volunteers
Roozekrans, M., Olofsen, E., van der Schrier, R. M., Boom, M., Mooren, R. A. G., & Dahan, A. (2016) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.601 · Cited by 14 · see citing works
Inhibition by intrathecal prazosin but not yohimbine of fentanyl-induced muscular rigidity in the rat
Lui, P.-W., Tsen, L.-Y., Fu, M.-J., Yeh, C.-P., Lee, T.-Y., & Chan, S. H. H. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)12162-5 · Cited by 14 · see citing works
THE EFFECT OF LEVORPHAN AND LEVALLORPHAN ON THE RESPIRATORY MECHANISM OF NORMAL MAN
Thomas, D. V., & Tenney, S. M. (1955) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)11509-7 · Cited by 14 · see citing works
Fentanyl overdose in a neonate: use of naloxone infusion
Ryan, J. P., & MEAKIN, G. (1989) · Anaesthesia · doi:10.1111/j.1365-2044.1989.tb09119.x · Cited by 12 · see citing works
Transdermal Fentanyl in Deliberate Overdose in Pediatrics
Lyttle, M. D., Verma, S., & Isaac, R. E. (2012) · Pediatric Emergency Care · doi:10.1097/pec.0b013e31825358b4 · Cited by 12 · see citing works
Accidental intrathecal sufentanil overdose during combined spinal-epidural analgesia for labor
Coleman, L., Carvalho, B., Lipman, S. S., Schmiesing, C. A., & Riley, E. T. (2008) · International Journal of Obstetric Anesthesia · doi:10.1016/j.ijoa.2008.10.001 · Cited by 11 · see citing works
Case 37-2017
Raja, A. S., Miller, E. S., Flores, E. J., Wakeman, S. E., & Eng, G. M. (2017) · New England Journal of Medicine · doi:10.1056/nejmcpc1710563 · Cited by 10 · see citing works
Infant and Toddler Ingestion of Illicit Fentanyl: A Case Series
Slingsby, B. A., Moore, J. L., & Barron, C. E. (2019) · Clinical Pediatrics · doi:10.1177/0009922819877870 · Cited by 9 · see citing works
PROLONGED BLOCKADE OF OPIOID EFFECTS WITH ORAL NALMEFENE
Gal, T. J., DiFazio, C. A., & Dixon, R. (1986) · Anesthesiology · doi:10.1097/00000542-198609001-00342 · Cited by 7 · see citing works
Naloxone should remain the appropriate antidote to treat opioid overdose
Mégarbane, B., Chevillard, L., & Vodovar, D. (2020) · Critical Care · doi:10.1186/s13054-020-2835-5 · Cited by 7 · see citing works
Do Patients Require Emergency Department Interventions After Prehospital Naloxone?
Fidacaro, G. A., Patel, P., Carroll, G. G., Bartimus, H. A., Hunter, K. M., & Hong, R. (2019) · Journal of Addiction Medicine · doi:10.1097/adm.0000000000000563 · Cited by 6 · see citing works
Safety of a Brief Emergency Department Observation Protocol for Patients With Presumed Fentanyl Overdose
Santos, C. D., Adam, A., Calello, D. P., & Nelson, L. S. (2018) · Annals of Emergency Medicine · doi:10.1016/j.annemergmed.2018.10.024 · Cited by 5 · see citing works
Fentanyl analogue overdose: Key lessons in management in the synthetic opioid age
Raheemullah, A., & Andruska, N. D. (2019) · Journal of Opioid Management · doi:10.5055/jom.2019.0531 · Cited by 5 · see citing works
Reversal of ingested fentanyl patch toxicity with oral naltrexone in remote Australia: case report
Wahl, G., & Gault, A. (2021) · Clinical Toxicology · doi:10.1080/15563650.2021.1882682 · Cited by 3 · see citing works
Antagonism of Fentanyl with Naloxone during N2O+O2+ Halothane Anaesthesia
Tigerstedt, I. (1977) · Acta Anaesthesiologica Scandinavica · doi:10.1111/j.1399-6576.1977.tb01248.x · Cited by 2 · see citing works
Willingness to Use a Wearable Device Capable of Detecting and Reversing Overdose Among People Who Use Opioids in PhiladelphiaPreprint
Kanter, K. N., Gallagher, R. S., Eweje, F. R., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-151919/v1 · Cited by 2 · see citing works

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Sorted by citations

Overdose mortality rates for opioids and stimulant drugs are substantially higher in men than in women: state-level analysis
Butelman, E. R., Huang, Y., Epstein, D. H., Shaham, Y., Goldstein, R. Z., Volkow, N. D., & Nelly Alia-klein, A. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-023-01601-8 · Cited by 91 · see citing works
“Overdose mortality from fentanyl may be greater than that for heroin, due to greater potency, faster onset of action driven by high lipophilicity, and higher likelihood to trigger chest rigidity [29 – 31].”
The ASAM/AAAP Clinical Practice Guideline on the Management of Stimulant Use Disorder
(2024) · Journal of Addiction Medicine · doi:10.1097/adm.0000000000001299 · Cited by 78 · see citing works
Tackling the challenges of developing microneedle-based electrochemical sensors
Abdullah, H., Phairatana, T., & Jeerapan, I. (2022) · Microchimica Acta · doi:10.1007/s00604-022-05510-3 · Cited by 56 · see citing works
Non-Fentanyl New Synthetic Opioids—An Update
Zawilska, J. B., Adamowicz, P., Kurpeta, M., & Wojcieszak, J. (2023) · Forensic Science International · doi:10.1016/j.forsciint.2023.111775 · Cited by 55 · see citing works
A Systematic Review on the Kappa Opioid Receptor and Its Ligands: New Directions for the Treatment of Pain, Anxiety, Depression, and Drug Abuse
Khan, M. I. H., Sawyer, B. J., Akins, N. S., & Le, H. V. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114785 · Cited by 52 · see citing works
Fact vs. fiction: naloxone in the treatment of opioid-induced respiratory depression in the current era of synthetic opioids
Dahan, A., Franko, T. S., Carroll, J. W., Craig, D. S., Crow, C., Galinkin, J. L., Garrity, J. C., Peterson, J., & Rausch, D. B. (2024) · Frontiers in Public Health · doi:10.3389/fpubh.2024.1346109 · Cited by 49 · see citing works
An Ultrasensitive Norfentanyl Sensor Based on a Carbon Nanotube-Based Field-Effect Transistor for the Detection of Fentanyl Exposure
Shao, W., Zeng, Z., & Star, A. (2023) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.3c05958 · Cited by 27 · see citing works
Examination of naloxone dosing patterns for opioid overdose by emergency medical services in Kentucky during increased fentanyl use from 2018 to 2021
Rock, P. J., Slavova, S. S., Westgate, P. M., Nakamura, A., & WALSH, S. L. (2023) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2023.111062 · Cited by 25 · see citing works
Self-citation
Collateral Damage: Neurological Correlates of Non-Fatal Overdose in the Era of Fentanyl-Xylazine
Todaro, D. R., Volkow, N. D., Langleben, D. D., Shi, Z., & Wiers, C. E. (2024) · Neuroscience Insights · doi:10.1177/26331055241247156 · Cited by 24 · see citing works
“16 Preclinical models demonstrate prolongation of brain oxygen decreases with co-administration of heroin and fentanyl that is more pronounced than either drug alone.”
The association of early naloxone use with outcomes in non-shockable out-of-hospital cardiac arrest
Strong, N. H., Daya, M. R., Neth, M. R., Noble, M., Sahni, R., Jui, J., & Lupton, J. R. (2024) · Resuscitation · doi:10.1016/j.resuscitation.2024.110263 · Cited by 21 · see citing works
IUPHAR review: Recent progress in the development of Mu opioid receptor modulators to treat opioid use disorders
Pagare, P. P., Flammia, R., & Zhang, Y. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.107023 · Cited by 18 · see citing works
American College of Medical Toxicology and the American Academy of Clinical Toxicology position statement: nalmefene should not replace naloxone as the primary opioid antidote at this time
Stolbach, A. I., Mazer-Amirshahi, M. E., Nelson, L. S., & Cole, J. B. (2023) · Clinical Toxicology · doi:10.1080/15563650.2023.2283391 · Cited by 16 · see citing works
“The original injectable nalmefene product was removed from the market for commercial reasons in 2008 [4,5].”
Background
Has the United States Reached a Plateau in Overdoses Caused by Synthetic Opioids After the Onset of the COVID-19 Pandemic? Examination of Centers for Disease Control and Prevention Data to November 2021
Brown, K. G., Chen, C. Y., Dong, D., Lake, K. J., & Butelman, E. R. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.947603 · Cited by 12 · see citing works
Patient perceptions of higher-dose naloxone nasal spray for opioid overdose
Strickland, J. C., Marks, K. R., Smith, K. E., Ellis, J. D., Hobelmann, J. G., & Huhn, A. S. (2022) · International Journal of Drug Policy · doi:10.1016/j.drugpo.2022.103751 · Cited by 14 · see citing works
A systematic review and meta-analysis of synthetic cathinone use and psychosis
Daswani, R., Choles, C. M., Kim, D. D., & Barr, A. M. (2024) · Psychopharmacology · doi:10.1007/s00213-024-06569-x · Cited by 13 · see citing works
“While the scope of this review focuses on SC consumption, we did not exclude studies that mention use of other substances as polysubstance use is a clinical reality for many who use drugs for recreational purposes (Britch and Walsh 2022; Hazani et al. 2022; Honer et al. 2017; Jones et al. 2020).”
Nalmefene Hydrochloride: Potential Implications for Treating Alcohol and Opioid Use Disorder
Green, M., Veltri, C. A., & Grundmann, O. (2024) · Substance Abuse and Rehabilitation · doi:10.2147/sar.s431270 · Cited by 13 · see citing works
Fentanyl blockade of K + channels contributes to wooden chest syndrome
Wei, A. D., Burgraff, N. J., Oliveira, L. M., Moreira, T. S., & Ramirez, J. (2025) · The Journal of Physiology · doi:10.1113/jp289107 · Cited by 12 · see citing works
“When recognized perioperatively, WCS is treated with competitive blockers of the nicotinic acetylcholine receptor, such as rocuronium, to reduce excessive muscle contraction by dampening neuromuscular transmission (Britch & Walsh, 2022; Jaffe & Ramsey, 1983).”
Development and preclinical testing of a naloxone prodrug depot for extended protection against opioid overdose
Aldawod, H., Patel, A. D., Emara, R., Liang, D., Ho, J. S., Amin, T. U., Tuhin, M. T. H., Balgoname, A. A., Kiani, A., Ajlouny, J. M., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-55945-4 · Cited by 11 · see citing works
The Role of Opioid Receptor Antagonists in Regulation of Blood Pressure and T-Cell Activation in Mice Selected for High Analgesia Induced by Swim Stress
Skiba, D. S., Jaskuła, K., Nawrocka, A., Poznański, P., Łazarczyk, M., Szymański, Ł., Żera, T., Sacharczuk, M., Cudnoch‐Jędrzejewska, A., & Gaciong, Z. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25052618 · Cited by 10 · see citing works
“Over the following decades, more experimental work was published describing the hypertensive effect of NAL in various species, such as rat, dog, and cat, along with studies on humans [3–7].”
BackgroundInfluential
Biological sex modulates the efficacy of 2,5-dimethoxy-4-iodoamphetamine (DOI) to mitigate fentanyl demand
McQueney, A. J., & Garcia, E. J. (2024) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2024.112426 · Cited by 10 · see citing works
Synaptic Structure and Transcriptomic Profiling of Reward and Sensory Brain Areas in Male Mice of Fentanyl Addiction
Feng, J., Xu, N., Wang, L., Wang, H., Zhou, Y., & Shen, Q. (2024) · Substance Abuse and Rehabilitation · doi:10.2147/sar.s484167 · Cited by 10 · see citing works
“43 Slc6a3 encodes dopamine transporter 1, an integral membrane protein responsible for recycling dopamine from the synaptic cleft back into the presynaptic neuron.”
Oxygen fluctuations in the brain and periphery induced by intravenous fentanyl: effects of dose and drug experience
Choi, S., Noya, M. R., & Kiyatkin, E. A. (2024) · Journal of Neurophysiology · doi:10.1152/jn.00177.2024 · Cited by 10 · see citing works
Transdermal delivery of naloxone hydrochloride using minimally invasive physical ablation techniques
Tijani, A. O., Dandekar, A. A., Karve, T., Banga, A. K., & Puri, A. (2023) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2023.123159 · Cited by 9 · see citing works
American College of Medical Toxicology and the American Academy of Clinical Toxicology Position Statement: Nalmefene Should Not Replace Naloxone as the Primary Opioid Antidote at This Time
Stolbach, A. I., Mazer-Amirshahi, M. E., Nelson, L. S., & Cole, J. B. (2023) · Journal of Medical Toxicology · doi:10.1007/s13181-023-00981-z · Cited by 9 · see citing works
“The original injectable nalmefene product was removed from the market for commercial reasons in 2008 [4, 5].”
Promising immunomodulators for management of substance and alcohol use disorders
Acuña, A. M., Park, C., Leyrer‐Jackson, J. M., & Olive, M. F. (2024) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2024.2360653 · Cited by 8 · see citing works
“The mixed MOR inverse agonist and weak partial KOR agonist nalmefene was approved for opioid over-dose treatment in 1995, but discontinued by the manufacturer in 2008, only to be reintroduced again in a nasal spray formulation as an opioid overdose countermeasure [45–47].”
Method
Correlates of stocking naloxone: a cross-sectional survey of community pharmacists
Laing, R., Xia, T., Grist, E., Dostal, J., Nielsen, S., & Picco, L. (2024) · International Journal of Clinical Pharmacy · doi:10.1007/s11096-024-01773-3 · Cited by 8 · see citing works
“Delivered as first aid either as an intramuscular injection or a nasal spray, it can rapidly and temporarily reverse the effects of opioid overdose [12].”
Naloxone Administration and Survival in Overdoses Involving Opioids and Stimulants: An Analysis of Law Enforcement Data from 63 Pennsylvania Counties
Cano, M. N., Jones, A. A., Silverstein, S. M., Daniulaityte, R., & LoVecchio, F. (2024) · International Journal of Drug Policy · doi:10.1016/j.drugpo.2024.104678 · Cited by 8 · see citing works
Bystander preference for naloxone products: a field experiment
Marks, K. R., Oyler, D. R., Strickland, J. C., Jaggers, J., Roberts, M. F., Miracle, D. K., Barnes, C., Lei, F., Smith, A., Mackin, E., et al. (2023) · Harm Reduction Journal · doi:10.1186/s12954-023-00904-9 · Cited by 7 · see citing works
“…lacking due to an array of pharmacokinetic factors (e.g., narrow response window due to rapidity of fentanyl-mediated overdose; adulterants that are non-responsive to opioid antagonists) and behavioral response factors (e.g., subjective dosage protocols and fidelity to dosing protocols) [10, 11].”
Background
Fentanyl–Antibody Interaction as a Novel Strategy against Opiates and Opioids Abuse
Ribaudo, G., Taccani, A. A., & Gianoncelli, A. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c02860 · Cited by 7 · see citing works
“The exploration of partial agonists, such as buprenorphine 75 and diprenorphine (Figure 7), 86 opioid compounds classified under the thebaine derivatives, has also been undertaken.”
Nalfurafine reverses fentanyl-induced muscle rigidity and respiratory depression without affecting sedation in rats: decoupling respiration from sedation
Lewis, T. H. J., & Haouzi, P. A. (2025) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00952.2024 · Cited by 7 · see citing works
Solid-Phase Synthesis of the Bicyclic Peptide OL-CTOP Containing Two Disulfide Bridges, and an Assessment of Its In Vivo μ-Opioid Receptor Antagonism after Nasal Administration
Rayala, R., Tiller, A., Majumder, S. A., Stacy, H. M., Eans, S. O., Nedovic, A., McLaughlin, J. P., & Čudić, P. (2023) · Molecules · doi:10.3390/molecules28041822 · Cited by 7 · see citing works
Postmortem toxicology findings from the Camden Opioid Research Initiative
Kusic, D., Heil, J., Zajic, S. C., Brangan, A., Dairo, O., Heil, S., Feigin, G., Kacinko, S. L., Buono, R. J., Ferraro, T. N., et al. (2023) · PLoS ONE · doi:10.1371/journal.pone.0292674 · Cited by 6 · see citing works
Respiratory Depression Associated with Opioids: A Narrative Review
Davis, M. P., DiScala, S., & Davis, A. L. (2024) · Current Treatment Options in Oncology · doi:10.1007/s11864-024-01274-5 · Cited by 7 · see citing works
Synthetic cannabinoid receptor agonists exacerbate fentanyl-elicited respiratory depression and confer resistance to naloxone rescue in mice
James, J. C., Thrush, J. R., Yusufali, T. M., Shaw, H. E., Avram, M., Moran, J. H., & Fantegrossi, W. E. (2025) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2025.112672 · Cited by 6 · see citing works
Comparison of ventilatory depression by carfentanil, fentanyl, and heroin, and reversal by opioid receptor antagonists in rats
Flynn, S. M., & France, C. P. (2025) · Neuropharmacology · doi:10.1016/j.neuropharm.2025.110601 · Cited by 6 · see citing works
Toward Developing Alternative Opioid Antagonists for Treating Community Overdose: A Model‐Based Evaluation of Important Pharmacological Attributes
Chaturbedi, A., Mann, J., Chakravartula, S., Thrasher, B., Arabidarrehdor, G., Zirkle, J., Meshkin, H., Nallani, S. C., Florian, J. A., & Li, Z. (2025) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.3527 · Cited by 6 · see citing works
“11,12 When reversing longer half-life opioids with a shorter half-life antagonist, such as nalox-one, there is a potential of renarcotization, which is opioid-induced secondary respiratory depression when the antagonist clears from the system before the agonist.”
Behavioural Effects and Naloxone Effectiveness With New Synthetic Opioids
Nielsen, S., Silva, J. P., Jones, J. D., Krotulski, A., Poovendran, D., Muzangizi, D., Forte, G., White, J., & Comer, S. D. (2026) · Drug and Alcohol Review · doi:10.1111/dar.70040 · Cited by 6 · see citing works
“…nalmefene has been proposed as an alternative for higher potency opioids, but the long half-life and risk of precipitating severe withdrawal [81] may limit its utility, particularly given the emerging evidence described here supporting that naloxone can be used effectively with nitazenes,…”
Reversing the triad of anaesthesia in a cannot intubate, cannot oxygenate emergency
Zhang, M., Liu, H., Han, X., Guo, J., & Ge, Y. (2024) · British Journal of Anaesthesia · doi:10.1016/j.bja.2024.04.020 · Cited by 5 · see citing works
The addictive process of opioids: current and novel interventions in opioid use disorder
Duerksen, J. M., Ramjiawan, M., Witt, J. C., Fitzpatrick-Wong, S. C., Tappia, P. S., Ramjiawan, B., Mansouri, B., Sareen, J., & Knight, E. (2025) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2024-0281 · Cited by 5 · see citing works
Reversal of Fentanyl‐Induced Respiratory Depression in Healthy Subjects by Intramuscular Nalmefene Administered by Auto‐Injector Versus Intranasal Naloxone
Cipriano, A., He, E., Shet, M. S., Apseloff, G., & Harris, S. (2025) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.70088 · Cited by 4 · see citing works
“38 Conversely, it may be possible that individuals who have received nalmefene could try to override the antagonist effect by taking additional doses of opioids, thus increasing the risk of overdose.”
A Single Ascending-Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Novel Respiratory Stimulant ENA-001
Pergolizzi, J. V., Miller, T. L., Mathews, J., Raffa, R. B., Colucci, R. D., Diana, F. J., & Gould, E. M. (2024) · Cureus · doi:10.7759/cureus.55057 · Cited by 4 · see citing works
“As a reversal agent, naloxone has limitations [21].”
Background
Tandospirone prevents anesthetic-induced respiratory depression through 5-HT1A receptor activation in rats
Song, M., Huang, M.-Z., Tao, W.-J., Yong, Z., & Su, R. (2025) · Scientific Reports · doi:10.1038/s41598-024-84440-x · Cited by 4 · see citing works
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Authors: Britch, S. C., & Walsh, S. L.
Affiliations: University of Kentucky (US)
Corresponding author: Walsh, Sharon L.
ORCID: Britch, Stevie C.
Walsh, Sharon L.
Venue: Psychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2022-04-07
Volume: 239
Issue: 7
Pages: 2063-2081
ISSN: 0033-3158 (ISSN-L)
1432-2072
DOI: 10.1007/s00213-022-06125-5
PMC: PMC8986509
OpenAlex: W4223464784
Cited by: 96
References: 110
Citations by year: 2026: 15 · 2025: 32 · 2024: 29 · 2023: 13 · 2022: 6
FWCI: 3.97
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Psychopharmacology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Drug Abuse (R01 DA016718, T32 DA035200)
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
Health Sciences › Medicine › Emergency Medicine › Poisoning and overdose treatments
Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords: opioid overdose, naloxone, fentanyl, fentanyl analogs, opioid epidemic, opioid antagonists, nalmefene, buprenorphine, respiratory stimulants
MeSH terms: Opiate Overdose, Analgesics, Opioid, Fentanyl, Humans, Naloxone, Narcotic Antagonists, Retrospective Studies, Illicit Drugs, Drug Overdose, Drug-Related Side Effects and Adverse Reactions

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