Kenneth Blum^1-4*, Alireza Sharafshah³,⁴, Kyriaki Thanos⁸, Frank Fornari³, Igor Elman¹,³,⁹, Edward J Modestino³,¹⁰, Morgan P Lorio³,¹¹, Debasis Bagchi³,¹², Rajendra D Badgaiyan³, Paul R Carney¹³, Albert Pinhasov¹, Abdalla Bowirrat¹, Rossano Kepler Alvim Fiorelli⁴, Sergio Schmidt⁴, Mark S Gold¹⁴, Keerthy Sunder²,³, Alexander PL Lewandrowski³, Mark Odron³, Álvaro Dowling³, Rafaela Dowling³, Joao Paulo Bergamaschi³ and Kai Uwe-Lewandrowski³,^4-7

¹Department of Molecular Biology, Adelson School of Medicine, Ariel University,
Ariel, Israel
²Division of Addiction Research and Education, Center for Sports, Exercise, and
Mental Health, Western University of Health Sciences, Pomona, USA
³Division of Clinical Neurology, The Origen Institute of Neurobiology and Genetics,
Austin, TX., USA
⁴Hospital Universitário Gaffree Guinle Universidade Federal do Estado do Rio de
Janeiro, Rio de Janeiro, Brazil
⁵Division of Personalized Pain Therapy Research and Education, Center for Ad-
vanced Spine Care of Southern Arizona, Tucson, USA
⁶Department of Orthopaedics, Federal University of the State of Rio de Janeiro,
Brazil
⁷Department of Surgery, Arizona University School of Medicine, Tucson, USA
⁸Department of Psychology, University of Buffalo, Buffalo, NY., USA
⁹Department of Psychiatry and Cambridge Health Alliance, Harvard Medical
School, Cambridge, USA
¹⁰Brain and Behavior Laboratory, Department of Psychology, Curry College, Milton,
MA, USA
¹¹Orlando College of Osteopathic Medicine, Winter Garden, FL, USA
¹²Department of Pharmaceutical Sciences, Texas Southern University College of
Pharmacy, Houston, TX, USA
¹³Departments of Pediatrics and Neurology, University of Missouri School of Medi-
cine, Columbia, Missouri, USA
¹⁴Department of Psychiatry, Washington University School of Medicine, USA

*Corresponding Author: Kenneth Blum, Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel.

Received: March 23, 2026; Published: April 29, 2026

Abstract

Opioid-induced “nodding” is commonly misinterpreted as benign sleep but represents a high-risk state of fluctuating conscious- ness caused by drug-induced respiratory depression. This condition may lead to progressive hypoxia and hypercapnia without nor- mal protective arousal. In the fentanyl era, nodding may reflect a subclinical overdose, with a dangerously narrow transition be- tween sedation and fatal respiratory failure, particularly when opioids are combined with alcohol, benzodiazepines, or other sedative agents. We utilized PUBMED to adopt various works linked to this important topic. Accumulating clinical and neuroimaging evidence suggests that repeated non-fatal overdose events and nodding episodes may contribute to cumulative hypoxic–ischemic brain injury, hippocampal volume loss, and persistent cognitive impairment. Current surveillance systems largely emphasize mortality, thereby underestimating the neurological burden among survivors. Public health and clinical frameworks should redefine nodding as a sen- tinel respiratory-compromise state and prioritize early intervention, expanded reporting, and improved harm-reduction strategies.

Keywords: Nodding; Sleep; Opioid Use Disorder (OUD)

References

1. Zacny JP., et al. “Comparing the subjective, psychomotor and physiological effects of intravenous buprenorphine and morphine in healthy volunteers”. Journal of Pharmacology and Experimental Therapeutics 3 (1997): 1187-1197.
2. Zacny JP., et al. “Comparing the subjective, psychomotor and physiological effects of intravenous pentazocine and morphine in normal volunteers”. Journal of Pharmacology and Experimental Therapeutics 3 (1998): 1197-1207.
3. Delaney McKinstry., et al. “Hippocampal volume and brain tau pathology in opioid use disorder: Associations with non-fatal opioid overdose”. Addiction Neuroscience 19 (2026): 100253.
4. Mahoney JJ. ., et al. “A pilot study investigating cognitive impairment associated with opioid overdose”. Drug and Alcohol Dependence 247 (2023): 109865.
5. Casillas SM., et al. “Estimating the ratio of fatal to non-fatal overdoses involving all drugs, all opioids, synthetic opioids, heroin or stimulants, USA, 2010-2020”. Injury Prevention2 (2024): 114-124.
6. Todaro D R., et al. “Hippocampal volume loss in individuals with a history of non-fatal opioid overdose”. Addiction Biology10 (2023): e13336.
7. Todaro DR., et al. “Collateral damage: Neurological correlates of non-fatal overdose in the era of fentanyl-xylazine”. Neuroscience Insights 19 (2024): 26331055241247156.
8. Lee YK., et al. “Opioid use disorder: current trends and potential treatments”. Frontiers in Public Health 11 (2024): 1274719.
9. Blum K., et al. “Improving naltrexone compliance and outcomes with putative pro- dopamine regulator KB220, compared to treatment as usual”. Journal of Systems and Integrative Neuroscience 7 (2020): 10.15761/JSIN.1000229.
10. Blum K., et al. “Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse”. EC Psychology and Psychiatry8 (2018): 564-579.
11. Chen TJ., et al. “Narcotic antagonists in drug dependence: pilot study showing enhancement of compliance with SYN-10, amino-acid precursors and enkephalinase inhibition therapy”. Medical Hypotheses3 (2004): 538-548.
12. Bartoli F., et al. “Association between depression and non-fatal overdoses among drug users: a systematic review and meta-analysis”. Drug Alcohol Dependence 134 (2014): 12-21.
13. Abrego-Guandique DM., et al. “The association between long-term opioid use and dementia risk: A systematic review and meta-analysis”. Progress in Neuro-Psychopharmacology and Biological Psychiatry 144 (2026): 111595.
14. Han Y., et al. “The rising crisis of illicit fentanyl use, overdose, and potential therapeutic strategies”. Translation Psychiatry1 (2019): 282.
15. Fischer LS., et al. “Effectiveness of naloxone distribution in community settings to reduce opioid overdose deaths among people who use drugs: a systematic review and meta-analysis”. BMC Public Health 1 (2025): 1135.
16. Casillas SM., et al. “Estimating the ratio of fatal to non-fatal overdoses involving all drugs, all opioids, synthetic opioids, heroin or stimulants, USA, 2010-2020”. Injury Prevention2 (2024): 114-124.
17. Demery C., et al. “Fentanyl decreases blood oxygen more than furanyl fentanyl despite similar effects on breathing”. Res Sq 12 (2026): rs.3.rs-8398857.
18. Wang Y., et al. “Opioid induces increased DNA damage in prefrontal cortex and nucleus accumbens”. Pharmacology Biochemistry and Behavior 224 (2023): 173535.
19. Boer OD., et al. “Adolescent substance use initiation and long-term neurobiological outcomes: insights, challenges and opportunities”. Molecular Psychiatry7 (2024): 2211-2222.
20. Blum K., et al. “rsfMRI effects of KB220Z™ on neural pathways in reward circuitry of abstinent genotyped heroin addicts”. Postgraduate Medicine2 (2015): 232-241.
21. Bensley KMK., et al. “Postmortem screening of opioids, benzodiazepines, and alcohol among rural and urban suicide decedents”. Journal of Rural Health1 (2022): 77-86.
22. Freire C., et al. “Opioids and obstructive sleep apnea”. Journal of Clinical Sleep Medicine2 (2022): 647-652.
23. Crews BO. “Recent advances in the identification and quantification of xylazine and medetomidine in biological specimens”. Bioanalysis20 (2025): 1295-1303.

Citation

Citation: Kenneth Blum., et al. “Opioid-Induced Nodding-Not a Nice Nap". Acta Scientific Neurology 9.5 (2026): 19-23.

Copyright

Copyright: ©2026 Kenneth Blum., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.