A Review on Fentanyl and The Neuroscientific Roots of Criminal Behaviour: Forensic and Legal Reflections
Main Article Content
Abstract
Background: The global diffusion of illicitly manufactured fentanyl represents a critical intersection between neuroscience, law, and public health. Originally developed as a potent analgesic in the XX century, fentanyl’s low production cost, chemical adaptability, and high lethality have enabled its rapid proliferation through transnational criminal networks. While North America remains the epicenter of the crisis, with synthetic opioids accounting for the majority of overdose deaths, recent evidence indicates the gradual expansion of fentanyl and its analogues into Europe, where emerging threats include nitazenes and xylazine-adulterated compounds.
Methods: This study adopts a multidisciplinary approach combining neuroscientific, criminological, and legal perspectives to analyze the roots and repercussions of fentanyl use and distribution. Through a systematic review of biomedical and legal literature, the research outlines the neurobiological mechanisms underlying opioid dependence, particularly the role of craving and impaired reward circuitry involving the mesolimbic dopaminergic system.
Results: These findings reveal structural and functional brain alterations that significantly affect volitional control, thereby challenging the traditional legal assumption of free will as a prerequisite for culpability.
Epidemiological data from 2019–2025 demonstrate a continuous rise in fentanyl-related mortality, particularly among adolescents and first-time users exposed to adulterated substances.
Conclusions: Although harm-reduction strategies, such as naloxone distribution, fentanyl test strips, and medication-assisted treatment, have yielded measurable benefits, they remain insufficient to counter the evolving complexity of synthetic opioid markets. Overall, the findings underscore the urgent need to align legal and criminal policy frameworks with neuroscientific evidence, promoting a balanced paradigm that integrates public health, justice, and human rights in addressing the global fentanyl crisis.
Article Details
How to Cite
POSA, F. et al.
A Review on Fentanyl and The Neuroscientific Roots of Criminal Behaviour: Forensic and Legal Reflections.
Medical Research Archives, [S.l.], v. 13, n. 11, dec. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7118>. Date accessed: 26 dec. 2025.
doi: https://doi.org/10.18103/mra.v13i11.7118.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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7. Stoecker WV, Bosworth KT, Rottnek F. Missouri’s Fen-tanyl Problem: The China Connection. Mo Med. 2020;117(4):362-369.
8. McDermott J. Mapping and Profiling the Most Threat-ening Criminal Networks in Latin America and the Carribean. EL PACCTO 2.0.; 2025. https://elpaccto.eu/wp-content/uploads/2025/02/ENG_Mapping-and-profiling-HRCN_LAC_Vpages.pdf
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11. Kronberg G, Goldstein RZ. An fMRI marker of drug and food craving. Nat Neurosci. 2023;26(2):178-180. doi:10.1038/s41593-022-01246-8
12. Barletta C, Di Natale V, Esposito M, et al. The Rise of Fentanyl: Molecular Aspects and Forensic Investiga-tions. IJMS. 2025;26(2):444. doi:10.3390/ijms26020444
13. Schembri E. Are Opioids Effective in Relieving Neu-ropathic Pain? SN Compr Clin Med. 2019;1(1): 30-46. doi:10.1007/s42399-018-0009-4
14. Karila L, Marillier M, Chaumette B, Billieux J, Franchitto N, Benyamina A. New synthetic opioids: Part of a new addiction landscape. Neurosci Biobe-hav Rev. 2019;106:133-140. doi:10.1016/j.neubiorev.2018.06.010
15. European Monitoring Centre for Drugs and Drug Ad-diction. Relazione europea sulla droga 2022: tendenze e sviluppi. Publications Office; 2022. Ac-cessed October 27, 2025. https://data.europa.eu/doi/10.2810/138286
16. Pereira JRP, Quintas A, Neng NR. Nitazenes: The Emergence of a Potent Synthetic Opioid Threat. Molecules. 2025;30(19):3890. doi:10.3390/molecules30193890
17. Ahmed S, Bhivandkar S, Lonergan BB, Suzuki J. Mi-croinduction of Buprenorphine/Naloxone: A Review of the Literature. Am J Addict. 2021;30(4):305-315. doi:10.1111/ajad.13135
18. Håkansson A, Widinghoff C, Abrahamsson T, Gede-on C. Correlates of Nine-Month Retention following Interim Buprenorphine-Naloxone Treatment in Opi-oid Dependence: A Pilot Study. Journal of Addiction. 2016;2016:1-8. doi:10.1155/2016/6487217
19. Crime UNO on D and. World Drug Report 2025 (Set of 3 Booklets). 1st ed. United Nations Research Insti-tute for Social Development; 2025.
20. Shaver T. The effects of escalated fentanyl intake on decision-making dynamics. Published online 2023. doi:10.13023/ETD.2023.182
21. Hogarth L, Field M. Relative expected value of drugs versus competing rewards underpins vulnera-bility to and recovery from addiction. Behav Brain Res. 2020;394:112815. doi:10.1016/j.bbr.2020.112815
22. Han Y, Cao L, Yuan K, Shi J, Yan W, Lu L. Unique Pharmacology, Brain Dysfunction, and Therapeutic Advancements for Fentanyl Misuse and Abuse. Neu-rosci Bull. 2022;38(11):1365-1382. doi:10.1007/s12264-022-00872-3
23. Kiyatkin EA, Choi S. Brain oxygen responses induced by opioids: focus on heroin, fentanyl, and their adul-terants. Front Psychiatry. 2024;15:1354722. doi:10.3389/fpsyt.2024.1354722
24. Todaro DR, Volkow ND, Langleben DD, Shi Z, Wiers CE. Collateral Damage: Neurological Correlates of Non-Fatal Overdose in the Era of Fentanyl-Xylazine. J Exp Neurosci. 2024;19:26331055241247156. doi:10.1177/26331055241247156
25. Wollman SC, Hauson AO, Hall MG, et al. Neuropsy-chological functioning in opioid use disorder: A re-search synthesis and meta-analysis. The American Journal of Drug and Alcohol Abuse. 2019;45(1):11-25. doi:10.1080/00952990.2018.1517262
26. Upadhyay J, Maleki N, Potter J, et al. Alterations in brain structure and functional connectivity in pre-scription opioid-dependent patients. Brain. 2010;133(7):2098-2114. doi:10.1093/brain/awq138
27. Dolinak D. Opioid Toxicity. Academic Forensic Pa-thology. 2017;7(1):19-35. doi:10.23907/2017.003
28. Lankhuijzen LM, Ridler T. Opioids, microglia, and temporal lobe epilepsy. Front Neurol. 2024;14: 1298489. doi:10.3389/fneur.2023.1298489
29. Withey SL, Cao L, de Moura FB, et al. Fentanyl-induced changes in brain activity in awake nonhu-man primates at 9.4 Tesla. Brain Imaging Behav. 2022;16(4):1684-1694. doi:10.1007/s11682-022-00639-4
30. Adler LJ, Gyulai FE, Diehl DJ, Mintun MA, Winter PM, Firestone LL. Regional brain activity changes as-sociated with fentanyl analgesia elucidated by posi-tron emission tomography. Anesth Analg. 1997;84(1):120-126. doi:10.1097/00000539-199701000-00023
31. Comer SD, Cahill CM. Fentanyl: Receptor pharma-cology, abuse potential, and implications for treat-ment. Neurosci Biobehav Rev. 2019;106:49-57. doi:10.1016/j.neubiorev.2018.12.005
32. Solis E, Cameron-Burr KT, Shaham Y, Kiyatkin EA. Fentanyl-Induced Brain Hypoxia Triggers Brain Hy-perglycemia and Biphasic Changes in Brain Temper-ature. Neuropsychopharmacol. 2018;43(4): 810-819. doi:10.1038/npp.2017.181
33. Tamargo JA, Campa A, Martinez SS, et al. Cognitive Impairment among People Who Use Heroin and Fen-tanyl: Findings from the Miami Adult Studies on HIV (MASH) Cohort. J Psychoactive Drugs. 2021;53(3): 215-223. doi:10.1080/02791072.2020.1850946
34. Keady J, Charnigo R, Shaykin JD, et al. Behavioral and genetic markers of susceptibility to escalate fen-tanyl intake. bioRxiv. Published online January 29, 2025:2024.12.06.627259. doi:10.1101/2024.12.06.627259
35. Takashina Y, Naito T, Mino Y, Yagi T, Ohnishi K, Kawakami J. Impact of CYP3A5 and ABCB1 gene polymorphisms on fentanyl pharmacokinetics and clinical responses in cancer patients undergoing con-version to a transdermal system. Drug Metab Phar-macokinet. 2012;27(4):414-421. doi:10.2133/dmpk.dmpk-11-rg-134
36. Zhu PF, Wang X, Nie B, et al. A neural circuit from paratenial thalamic nucleus to anterior cingulate cor-tex for the regulation of opioid-induced hyperalge-sia in male rats. Neurobiology of Disease. 2024;203:106745. doi:10.1016/j.nbd.2024.106745
37. Fields HL, Margolis EB. Understanding opioid re-ward. Trends Neurosci. 2015;38(4):217-225. doi:10.1016/j.tins.2015.01.002
38. Taylor JL, Samet JH. Opioid Use Disorder. Ann Intern Med. 2022;175(1):ITC1-ITC16. doi:10.7326/AITC202201180
39. Wakeman SE. Opioid Use Disorder Diagnosis and Management. NEJM Evid . 2022;1(4):EVIDra2200038. doi:10.1056/EVIDra2200038
40. Calihan JB, Carney BL, Schmill DM, Bagley SM. The Call for a School-Based Approach to Opioid Over-dose Prevention. Am J Public Health. 2024;114(12): 1305-1308. doi:10.2105/AJPH.2024.307849
41. Kuehn BM. Fentanyl Drives Startling Increases in Ad-olescent Overdose Deaths. JAMA. 2023;329(4): 280-281. doi:10.1001/jama.2022.23563
42. McKnight C, Weng CA, Reynoso M, Kimball S, Thompson LM, Jarlais DD. Understanding intention-ality of fentanyl use and drug overdose risk: Find-ings from a mixed methods study of people who in-ject drugs in New York City. International Journal of Drug Policy. 2023;118:104063. doi:10.1016/j.drugpo.2023.104063
43. Pilarinos A, Bromberg DJ, Karamouzian M. Access to Medications for Opioid Use Disorder and Associated Factors Among Adolescents and Young Adults: A Sys-tematic Review. JAMA Pediatr. 2022;176(3):304-311. doi:10.1001/jamapediatrics.2021.4606
44. Zang X, Skinner A, Krieger MS, et al. Evaluation of Strategies to Enhance Community-Based Naloxone Distribution Supported by an Opioid Settlement. JAMA Netw Open. 2024;7(5):e2413861. doi:10.1001/jamanetworkopen.2024.13861
45. Messinger JC, Beletsky L, Kesselheim AS, Barenie RE. Moving Naloxone Over the Counter Is Necessary but Not Sufficient. Ann Intern Med. 2023;176(8):1109-1112. doi:10.7326/M23-0852
46. Rife T, Tat C, Jones J, Pennington DL. An initiative to increase opioid overdose education and naloxone distribution for homeless veterans residing in con-tracted housing facilities. J Am Assoc Nurse Pract. 2021;34(1):188-195. doi:10.1097/JXX.0000000000000577
47. Wang N, Ou Y, Wang Y, Huang Z, Hu Y, Zhao S. Xylazine-Adulterated Fentanyl-Induced Brain Toxici-ty: Mechanism Elucidation via Network Toxicology and Molecular Docking Approaches. J Appl Toxicol. Published online August 23, 2025. doi:10.1002/jat.4902
48. Vickers-Smith RA, Gelberg KH, Childerhose JE, et al. Fentanyl Test Strip Use and Overdose Risk Reduction Behaviors Among People Who Use Drugs. JAMA Netw Open. 2025;8(5):e2510077. doi:10.1001/jamanetworkopen.2025.10077
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