Acute Olfactory Hypersensitivity to Opium and Cannabis Following Naltrexone Administration: A Rare Case Report

Document Type : Case Report(s)

Authors

1 Psychosomatic Research Center, Sari Imam Khomeini Hospital, Mazandaran University of Medical Sciences, Sari, Iran

2 Psychiatry and Behavioral Sciences Research Center, Addiction Institute, Mazandaran University of Medical Sciences, Sari, Iran

10.34172/ahj.1746

Abstract

Naltrexone, a long-acting opioid receptor antagonist, is commonly utilized to avert relapse in individuals with opioid or alcohol dependence. While its efficacy in modifying cue-reactivity and lowering desire is well documented, less is known regarding its ability to elicit negative sensory-emotional reactions, particularly in response to olfactory stimulation. We present a rare case of a 16-year-old male with a history of cannabis usage who experienced acute episodes of respiratory distress after starting oral naltrexone (50 mg/day). These episodes were consistently triggered by the smell of opium or cannabis smoke, despite the patient’s abstinence. The reactions were severe enough to necessitate multiple emergency medical procedures. The patient had a prior adverse reaction to morphine and a history of multiple drug allergies, suggesting a possible underlying sensitivity to opioid system modulation. The symptoms resolved after discontinuation of naltrexone. This case raises significant clinical and neurobiological concerns about the role of opioid antagonism in modifying olfactory and emotional processing. We propose that naltrexone-induced disinhibition in olfactory-limbic circuits may have contributed to heightened sensory gain and conditioned unpleasant reactions in a sensitized individual. More research is needed to understand the mechanisms driving this unusual yet important reaction.

Highlights

Raheleh Rafaiee(Google scholar)(Pubmed)

Keywords

References

  1. Sudakin D. Naltrexone: not just for opioids anymore. J Med Toxicol 2016;12(1):71-5. doi:10.1007/s13181-015-0512-x
  2. Kumar R, Quraishi R, Sarkar S, Rao R, Ambekar A. Naltrexone and its effects on craving and alcohol use among patients with alcohol dependence syndroms: a report. Addict Health 2024;16(3):224-7. doi:10.34172/ahj.1494
  3. Duerksen J, Ramjiawan M, Witt J, Fitzpatrick-Wong S, Tappia P, Ramjiawan B, et al. The addictive process of opioids: current and novel interventions in opioid use disorder. Can J Physiol Pharmacol 2025;103(4):111-22. doi:10.1139/cjpp-2024-0281
  4. Bolton M, Hodkinson A, Boda S, Mould A, Panagioti M, Rhodes S, et al. Serious adverse events reported in placebo randomised controlled trials of oral naltrexone: a systematic review and meta-analysis. BMC Med 2019;17(1):10. doi:10.1186/s12916- 018-1242-0
  5. Ploesser J, Weinstock LB, Thomas E. Low dose naltrexone: side effects and efficacy in gastrointestinal disorders. Int J Pharm Compd 2010;14(2):171-3.
  6. Courtney KE, Ghahremani DG, Ray LA. The effects of pharmacological opioid blockade on neural measures of drug cue-reactivity in humans. Neuropsychopharmacology 2016;41(12):2872-81. doi:10.1038/npp.2016.99
  7. Wang ZY, Guo LK, Han X, Song R, Dong GM, Ma CM, et al. Naltrexone attenuates methamphetamine-induced behavioral sensitization and conditioned place preference in mice. Behav Brain Res 2021;399:112971. doi:10.1016/j.bbr.2020.112971
  8. Hyman SM, Fox H, Hong KI, Doebrick C, Sinha R. Stress and drug-cue-induced craving in opioid-dependent individuals in naltrexone treatment. Exp Clin Psychopharmacol 2007;15(2):134-43. doi:10.1037/1064-1297.15.2.134
  9. Lukas SE, Lowen SB, Lindsey KP, Conn N, Tartarini W, Rodolico J, et al. Extended-release naltrexone (XR-NTX) attenuates brain responses to alcohol cues in alcohol-dependent volunteers: a bold FMRI study. Neuroimage 2013;78:176-85. doi:10.1016/j. neuroimage.2013.03.055
  10. Agarwal K, McDuffie C, Manza P, Joseph PV. Taste and smell alterations and substance use disorders. In: Joseph PV, Duffy VB, eds. Sensory Science and Chronic Diseases: Clinical Implications and Disease Management. Cham: Springer International Publishing; 2021. p. 159-79. doi:10.1007/978- 3-030-86282-4_8
  11. Bertino M, Beauchamp GK, Engelman K. Naltrexone, an opioid blocker, alters taste perception and nutrient intake in humans. Am J Physiol 1991;261(1 Pt 2): R59-63. doi:10.1152/ ajpregu.1991.261.1.R59
  12. Eikemo M, Løseth GE, Johnstone T, Gjerstad J, Willoch F, Leknes S. Sweet taste pleasantness is modulated by morphine and naltrexone. Psychopharmacology (Berl) 2016;233(21- 22):3711-23. doi:10.1007/s00213-016-4403-x
  13. Bajracharya SR, Ghimire R, Gyanwali P, Khadka A. Causality assessment of adverse drug reaction using Naranjo probability scale: a retrospective study. Med J Shree Birendra Hosp 2020;19(1):16-9. doi:10.3126/mjsbh.v19i1.21573
  14. Tabanelli R, Brogi S, Calderone V. Targeting opioid receptors in addiction and drug withdrawal: where are we going? Int J Mol Sci 2023;24(13):10888. doi:10.3390/ijms241310888
  15. Niciu MJ, Arias AJ. Targeted opioid receptor antagonists in the treatment of alcohol use disorders. CNS Drugs 2013;27(10):777- 87. doi:10.1007/s40263-013-0096-4
  16. Wardle MC, Bershad AK, de Wit H. Naltrexone alters the processing of social and emotional stimuli in healthy adults. Soc Neurosci 2016;11(6):579-91. doi:10.1080/17470919.20 15.1136355
  17. Cabrera EA, Wiers CE, Lindgren E, Miller G, Volkow ND, Wang GJ. Neuroimaging the effectiveness of substance use disorder treatments. J Neuroimmune Pharmacol 2016;11(3):408-33. doi:10.1007/s11481-016-9680-y
  18. Murata K, Maegawa A, Imoto Y, Fujieda S, Fukazawa Y. Endogenous opioids in the olfactory tubercle and their roles in olfaction and quality of life. Front Neural Circuits 2024;18:1408189. doi:10.3389/fncir.2024.1408189
  19. Volkow ND, Michaelides M, Baler R. The neuroscience of drug reward and addiction. Physiol Rev 2019;99(4):2115-40. doi:10.1152/physrev.00014.2018
  20. Lueptow LM, Shashkova EC, Miller MG, Evans CJ, Cahill CM. Insights into the neurobiology of craving in opioid use disorder. Curr Anesthesiol Rep 2020;10(4):378-87. doi:10.1007/s40140- 020-00420-7
  21. Latif ZE, Šaltyte Benth J, Solli KK, Opheim A, Kunoe N, Krajci P, et al. Anxiety, depression, and insomnia among adults with opioid dependence treated with extended-release naltrexone vs buprenorphine-naloxone: a randomized clinical trial and follow-up study. JAMA Psychiatry 2019;76(2):127-34. doi: https://doi.org/10.1001/jamapsychiatry.2018.3537
Addiction & Health
Volume 18
Pages 1-4

Files

Share

How to cite

Statistics