Levamisole: A High Performance Cutting Agent
Abstract
Levamisole is an imidazothiazole chemical most frequently used as an antihelminthic agent in cattle. Over the last decade, levamisole has been increasingly encountered as an additive in both powder and crack cocaine. A white powder with a “fish scale” appearance, the chemical is physically similar to powder cocaine. In vivo, levamisole is metabolized to aminorex, a compound with amphetamine-like psychostimulatory properties and a long half-life; a priori, this property allows levamisole to potentiate and prolong the stimulatory effects of cocaine while bulking up the drug to increase profit for the dealer. As use of cocaine cut with levamisole becomes more prevalent, complications directly attributable to the chemical are increasingly being recognized.
Get full access to this article
View all access and purchase options for this article.
References
1. Hofmaier T. Luf A. Seddik A.et al. Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters. Neurochem Int. 2014 Jul; 73: 32–41. 24296074. PMCID: PMC4077236. https://doi.org/10.1016/j.neuint.2013.11.010.
2. Maraj S. Figueredo V.M. Lynn Morris D. Cocaine and the heart. Clin Cardiol. 2010 May; 33(5): 264–9. 20513064. https://doi.org/10.1002/clc.20746.
3. Lohoff F.W. Weller A.E. Bloch P.J.et al. Association between the catechol-O-methyltransferase Val158Met polymorphism and cocaine dependence. Neuropsychopharmacology. 2008 Dec; 33(13): 3078–84. 18704099. PMCID: PMC2583214. https://doi.org/10.1038/npp.2008.126.
4. Cole C. Jones L. McVeigh J.et al. CUT: a guide to adulterants, bulking agents and other contaminants found in illicit drugs. Liverpool: Centre for Public Health, 2010. 58 p.
5. Lapachinske S.F. Okai G.G. dos Santos A.et al. Analysis of cocaine and its adulterants in drugs for international trafficking seized by the Brazilian Federal Police. Forensic Sci Int. 2015 Feb; 247: 48–53. 25544694. https://doi.org/10.1016/j.forsciint.2014.11.028.
6. Schneider S. Meys F. Analysis of illicit cocaine and heroin samples seized in Luxembourg from 2005-2010. Forensic Sci Int. 2011 Oct 10; 212(1-3): 242–6. 21767923. https://doi.org/10.1016/j.forsciint.2011.06.027.
7. Broseus J. Gentile N. Esseiva P. The cutting of cocaine and heroin: a critical review. Forensic Sci Int. 2016 May; 262: 73–83. 26974713. https://doi.org/10.1016/j.forsciint.2016.02.033.
8. Pawlik E. Mahler H. Hartung B.et al. Drug-related death: adulterants from cocaine preparations in lung tissue and blood. Forensic Sci Int. 2015 Apr; 249: 294–303. 25747329. https://doi.org/10.1016/j.forsciint.2015.02.006.
9. Centers for Disease Control and Prevention (CDC). Agranulocytosis associated with cocaine use - four States, March 2008-November 2009. MMWR Morb Mortal Wkly Rep. 2009 Dec 18; 58(49): 1381–5. 20019655.
10. Tallarida C.S. Egan E. Alejo G.D.et al. Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine's action in vivo. Neuropharmacology. 2014 Apr; 79: 590–5. 24440755. PMCID: PMC3989204. https://doi.org/10.1016/j.neuropharm.2014.01.002.
11. Tallarida C.S. Tallarida R.J. Rawls S.M. Levamisole enhances the rewarding and locomotor-activating effects of cocaine in rats. Drug Alcohol Depend. 2015 Apr 1; 149: 145–50. 25683823. PMCID: PMC4447121. https://doi.org/10.1016/j.drugalcdep.2015.01.035.
12. Le Garff E. Tournel G. Becquart C.et al. Extensive necrotic purpura in levamisole-adulterated cocaine abuse - a case report. J Forensic Sci. 2016 Nov; 61(6): 1681–1685. 27500987. https://doi.org/10.1111/1556-4029.13176.
13. Coles G.C. East J.M. Jenkins S.N. The mechanism of action of the antihelmintic levamisole. Gen Pharmacol Vasc Syst. 1975; 6(4): 309–13. https://doi.org/10.1016/0306-3623(75)90030-0.
14. Karch S.B. Busardò F.P. Vaiano F.et al. Levamisole adulterated cocaine and pulmonary vasculitis: presentation of two lethal cases and brief literature review. Forensic Sci Int. 2016 Aug; 265: 96–102. 26855022. https://doi.org/10.1016/j.forsciint.2016.01.015.
15. Michaud K. Grabherr S. Shiferaw K.et al. Acute coronary syndrome after levamisole-adultered cocaine abuse. J Forensic Leg Med. 2014 Jan; 21: 48–52. 24365689. https://doi.org/10.1016/j.jflm.2013.10.015.
16. Karch S.B. Mari F. Bartolini V. Bertol E. Aminorex poisoning in cocaine abusers. Int J Cardiol. 2012 Jul 26; 158(3): 344–6. 21764154. https://doi.org/10.1016/j.ijcard.2011.06.105.
17. Ho E.N. Leung D.K. Leung G.N.et al. Aminorex and rexamino as metabolites of levamisole in the horse. Anal Chim Acta. 2009 Apr 6; 638(1): 58–68. 19298880. https://doi.org/10.1016/j.aca.2009.02.033.
18. Chung C. Tumeh P.C. Birnbaum R.et al. Characteristic purpura of the ears, vasculitis, and neutropenia–a potential public health epidemic associated with levamisole-adulterated cocaine. J Am Acad Dermatol. 2011 Oct; 65(4): 722–5. 21658797. PMCID: PMC4000158. https://doi.org/10.1016/j.jaad.2010.08.024.
19. Isner J.M. Estes NA 3rd Thompson P.D.et al. Acute cardiac events temporally related to cocaine abuse. N Engl J Med. 1986 Dec 4; 315(23): 1438–43. 3785295. https://doi.org/10.1056/NEJM198612043152302.
20. Stankowski R.V. Kloner R.A. Rezkalla S.H. Cardiovascular consequences of cocaine use. Trends Cardiovasc Med. 2015 Aug; 25(6): 517–26. 25657055. https://doi.org/10.1016/j.tcm.2014.12.013.
21. Phillips K. Luk A. Soor G.S.et al. Cocaine cardiotoxicity: a review of the pathophysiology, pathology, and treatment options. Am J Cardiovasc Drugs. 2009; 9(3): 177–96. 19463023. https://doi.org/10.1007/bf03256574.
22. Talarico G.P. Crosta M.L. Giannico M.B.et al. Cocaine and coronary artery diseases: a systematic review of the literature. J Cardiovasc Med (Hagerstown). 2017 May; 18(5): 291–294. 28306693. https://doi.org/10.2459/JCM.0000000000000511.
23. Hantson P. Di Fazio V. Del Mar Ramirez Fernandez M.et al. Susaclike syndrome in a chronic cocaine abuser: could levamisole play a role? J Med Toxicol. 2015 Mar; 11(1): 124–8. 25142038. PMCID: PMC4371041. https://doi.org/10.1007/s13181-014-0422-3.
24. Brajković G. Babić G. Stosić J.J.et al. Fatal cocaine intoxication in a body packer. Vojnosanit Pregl. 2016 Feb; 73(2): 198–201. 27071289. https://doi.org/10.2298/vsp141105022b.
25. Baselt R.C. Disposition of toxic drugs and chemicals in man. 10th ed. Seal Beach (CA): Biomedical Publications; 2014. 2211 p.
26. Kouassi E. Caillé G. Léry L.et al. Novel assay and pharmacokinetics of levamisole and p-hydroxylevamisole in human plasma and urine. Biopharm Drug Dispos. 1986 Jan-Feb; 7(1): 71–89. 3754161. https://doi.org/10.1002/bdd.2510070110.
27. Hess C. Ritke N. Broecker S.et al. Metabolism of levamisole and kinetics of levamisole and aminorex in urine by means of LC-QTOFHRMS and LC-QqQ-MS. Anal Bioanal Chem. 2013 May; 405(12): 4077–88. 23436169. https://doi.org/10.1007/s00216-013-6829-x.
28. Nolan A.L. Jen K.Y. Pathologic manifestations of levamisole-adulterated cocaine exposure. Diagn Pathol. 2015 May 6; 10: 48. 25943359. PMCID: PMC4419488. https://doi.org/10.1186/s13000-015-0279-z.
29. Buxton J.A. Omura J. Kuo M.et al. Genetic determinants of cocaine-associated agranulocytosis. BMC Res Notes. 2015 Jun 13; 8: 240. 26070312. PMCID: PMC4467676. https://doi.org/10.1186/s13104-015-1219-4.
30. Indorato F. Romano G. Barbera N. Levamisole-adulterated cocaine: Two fatal case reports and evaluation of possible cocaine toxicity potentiation. Forensic Sci Int. 2016 Aug; 265: 103–6. 26866560. https://doi.org/10.1016/j.forsciint.2016.01.005.
31. Vosoughi R. Schmidt B.J. Multifocal leukoencephalopathy in cocaine users: a report of two cases and review of the literature. BMC Neurol. 2015 Oct 19; 15: 208. 26482228. PMCID: PMC4615875. https://doi.org/10.1186/s12883-015-0467-1.
32. Karch S.B. Defraia B. Messerini L.et al. Aminorex associated with possible idiopathic pulmonary hypertension in a cocaine user. Forensic Sci Int. 2014 Jul; 240: e7–10. 24794740. https://doi.org/10.1016/j.forsciint.2014.03.028.
Cite
Cite
Cite
OR
Download to reference manager
If you have citation software installed, you can download citation data to the citation manager of your choice
Information, rights and permissions
Information
Published In
Article first published online: September 1, 2017
Issue published: September 2017
Keywords
PubMed: 31239995
Authors
Metrics and citations
Metrics
Journals metrics
This article was published in Academic Forensic Pathology.
View All Journal MetricsPublication usage*
Total views and downloads: 483
*Publication usage tracking started in December 2016
Publications citing this one
Receive email alerts when this publication is cited
Web of Science: 0
Crossref: 36
- Detected substances among patients with confirmed bromazolam exposure who present to the emergency department following a suspected opioid and/or stimulant-related non-fatal overdose
- Method development: testing the efficiency of six DNA extraction kits on ten drug adulterants
- Psychostimulant and opioid abuse: A perspective from Uruguay
- Consumers Believe Legal Products Are Less Effective Than Illegal Products
- Wound-associated agents in the unregulated drug supply: Evidence from a statewide drug checking program
- Development and evaluation of a nontargeted electrochemical surface-enhanced Raman spectroscopy (EC-SERS) screening method applied to forensic seized drug casework samples
- Levamisole Ameliorates Rheumatoid Arthritis by Downregulating the PI3K/Akt Pathway in SD Rats
- Violaceous nodules of the extensor joints – a clinicopathological challenge
- Brain alterations in Cocaine Use Disorder: Does the route of use matter and does it relate to the treatment outcome?
- Tolerant or Intolerant? Learning From Studying Drug Concentrations in the Living and the Dead
- View More
Figures and tables
Figures & Media
Tables
View Options
Access options
If you have access to journal content via a personal subscription, university, library, employer or society, select from the options below:
I am signed in as:
View my profileSign out
I can access personal subscriptions, purchases, paired institutional access and free tools such as favourite journals, email alerts and saved searches.
loading institutional access options
NAME Foundation members can access this journal content using society membership credentials.
NAME Foundation members can access this journal content using society membership credentials.
Alternatively, view purchase options below:
Purchase 24 hour online access to view and download content.
Access journal content via a DeepDyve subscription or find out more about this option.
