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1.
Amery WK, Bruynseels JP. Levamisole, the story and the lessons.  Int J Immunopharmacol. 1992;14(3):481-486PubMedArticle
2.
Rongioletti F, Ghio L, Ginevri F,  et al.  Purpura of the ears: a distinctive vasculopathy with circulating autoantibodies complicating long-term treatment with levamisole in children.  Br J Dermatol. 1999;140(5):948-951PubMedArticle
3.
Valentino AM, Fuentecilla K. Levamisole: an analytical profile.  Microgram J. 2005;3(3-4):134-137
4.
 Drug intelligence brief: Cocaine containing levamisole adversely affecting drug users in the United States [DEA-10001-levamisole]. Drug Enforcement Administration, Intelligence Production Unit. January 2010
5.
Spector S, Munjal I, Schmidt DE. Effects of the immunostimulant, levamisole, on opiate withdrawal and levels of endogenous opiate alkaloids and monoamine neurotransmitters in rat brain.  Neuropsychopharmacology. 1998;19(5):417-427PubMedArticle
6.
Chang A, Osterloh J, Thomas J. Levamisole: a dangerous new cocaine adulterant.  Clin Pharmacol Ther. 2010;88(3):408-411PubMedArticle
Citations 0
Research Letter
April 27, 2011

Prevalence of Levamisole in Urine Toxicology Screens Positive for Cocaine in an Inner-City Hospital

JAMA. 2011;305(16):1657-1658. doi:10.1001/jama.2011.531

To the Editor: Cocaine use is prevalent in the United States. Recently, we encountered multiple patients at our institution with unexplained agranulocytosis or cutaneous vasculitis. All had used cocaine contaminated with levamisole. Although levamisole is known to be present in cocaine specimens, it is not clear how often levamisole exposure from cocaine use leads to systemic levamisole absorption. The objective of this study was to determine the prevalence of levamisole in urine toxicology screens positive for cocaine in a 500-bed public safety-net hospital with 160 000 unique patient users in 2010.

Methods

Consecutive urine toxicology samples received by the hospital laboratory that tested positive for cocaine by immunoassay (Syva EMIT II; Siemens Healthcare Diagnostics, Deerfield, Illinois) were sent to the Colorado Department of Public Health for comprehensive drug analysis (including levamisole) using gas chromatography–mass spectroscopy (GC/MS). Proportions of samples (and 95% confidence intervals [CIs]) positive for cocaine, levamisole, and other drugs of abuse were calculated. The study was approved by our institutional review board with a waiver of informed consent. No patient identifying, demographic, or clinical data were collected. JMP version 8.0 was used for statistical analysis (SAS Institute. Cary, North Carolina).

Results

Three hundred samples were obtained from April 14, 2010, to July 13, 2010. Although all of the samples were positive for cocaine by immunoassay, only 249 of 300 samples (83%; 95% CI, 78%-87%) were positive for cocaine by GC/MS. Of the samples positive for cocaine by GC/MS, 194 of 249 (78%; 95% CI, 73%-83%) contained levamisole. Of the samples negative for cocaine by GC/MS, 9 of 51 (18%; 95% CI, 10%-30%) contained levamisole. The overall proportion of samples positive for levamisole was 203 of 300 (68%; 95% CI, 63%-73%). The most common other drugs found in the specimens were opioid analgesics (methadone, n = 134, 45% of samples; codeine, n = 50, 16%; heroin/6-monoacetylmorphine, n = 17, 6%; morphine, n = 15, 5%; and oxycodone, n = 15, 5%).

Comment

This study demonstrates that levamisole used to adulterate cocaine was systemically absorbed by cocaine users and, in 1 institution, was common in urine samples positive for cocaine. The 17% of samples positive for cocaine by immunoassay but negative by GC/MS may be due to degradation of cocaine metabolites during storage. The low incidence of levamisole present in samples alone without cocaine may indicate a more rapid degradation or excretion of cocaine metabolites compared with levamisole metabolites.

Although developed as an antihelminthic agent, levamisole has also been used to treat various autoimmune disorders and cancers in humans.1 Levamisole increases T-cell activation and proliferation, neutrophil mobility, adherence, and chemotaxis and increases the formation of antibodies to antigens.1,2 It also acts as a hapten, triggering an immune response resulting in the opsonization and destruction of leukocytes.1,2 The US Drug Enforcement Agency (DEA) first detected levamisole in cocaine bricks in 2003.3 DEA data indicate that 44.1% of drug specimens tested in 2008 contained levamisole, increasing to 73.2% in 2009.4 The reason for cutting cocaine with levamisole is unclear but likely because levamisole is a widely available, cheap white powder thought to increase the euphoric and stimulatory effects of cocaine by increasing brain dopamine levels and forming amphetamine-like metabolites.5,6 Unfortunately, levamisole can result in life-threatening agranulocytosis, leukoencephalopathy, and cutaneous vasculitides.1,2

This study is limited because it was a single-center study; no clinical data on patients were collected; and although we attempted to collect consecutive samples, it is possible that some were missed. Given the high prevalence of levamisole in the cocaine supply, physicians should consider levamisole exposure in cocaine users with unexplained agranulocytosis, leukoencephalopathy, or cutaneous vasculitis.

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Article Information

Author Contributions: Dr Buchanan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Buchanan, Heard, Burbach, Wilson, Dart.

Acquisition of data: Buchanan, Heard, Burbach, Wilson.

Analysis and interpretation of data: Buchanan, Heard, Burbach.

Drafting of the manuscript: Buchanan, Burbach.

Critical revision of the manuscript for important intellectual content: Buchanan, Heard, Burbach, Wilson, Dart.

Statistical analysis: Buchanan, Heard, Burbach.

Obtained funding: Buchanan, Burbach, Dart.

Administrative, technical, or material support: Buchanan, Burbach, Wilson.

Study supervision: Dart.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Funding/Support: This work was supported by an intramural research grant from the Rocky Mountain Poison and Drug Center. Dr Heard was supported by award K08DA020573 from the National Institute on Drug Abuse.

Role of the Sponsor: The sponsor had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Drug Abuse or the National Institutes of Health.

Additional Contributions: We thank Vanessa Simmons, BA, Department of Public Health, Denver, Colorado, for specimen analysis and Brooke Bender, MSPH, Denver Health and Hospital Authority, Denver, for study coordination. Neither received compensation.

References
1.
Amery WK, Bruynseels JP. Levamisole, the story and the lessons.  Int J Immunopharmacol. 1992;14(3):481-486PubMedArticle
2.
Rongioletti F, Ghio L, Ginevri F,  et al.  Purpura of the ears: a distinctive vasculopathy with circulating autoantibodies complicating long-term treatment with levamisole in children.  Br J Dermatol. 1999;140(5):948-951PubMedArticle
3.
Valentino AM, Fuentecilla K. Levamisole: an analytical profile.  Microgram J. 2005;3(3-4):134-137
4.
 Drug intelligence brief: Cocaine containing levamisole adversely affecting drug users in the United States [DEA-10001-levamisole]. Drug Enforcement Administration, Intelligence Production Unit. January 2010
5.
Spector S, Munjal I, Schmidt DE. Effects of the immunostimulant, levamisole, on opiate withdrawal and levels of endogenous opiate alkaloids and monoamine neurotransmitters in rat brain.  Neuropsychopharmacology. 1998;19(5):417-427PubMedArticle
6.
Chang A, Osterloh J, Thomas J. Levamisole: a dangerous new cocaine adulterant.  Clin Pharmacol Ther. 2010;88(3):408-411PubMedArticle
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