The Possible Role of Levamisole in Illicit Cocaine Preparations

Raymon, Lionel P.; Isenschmid, Daniel S.

doi:10.1093/jat/33.9.620

Cited by 52 publications

(38 citation statements)

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“…Given the relatively low percentage present, varying between 2 and 10%, it has been postulated that levamisole is added for expected pharmacologic effects (20). Levamisole acts as a nicotinic acetylcholine receptor agonist and stimulates the sympathetic nervous system (41). In animal models, it has been shown to alter central metabolism of norepinephrine, dopamine, and serotonin, and attenuate symptoms of opiate withdrawal (42).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it has been proposed that levamisole may potentiate the impact of increased dopamine release induced by cocaine. Furthermore, these peripheral and central actions could combine synergistically to increase the perceived effects from cocaine use and, possibly, its addictive potential (41). Finally, others have suggested that due to similar physical properties to cocaine, levamisole may be more difficult to detect as an adulterant than other more commonly used agents.…”

Section: Discussionmentioning

confidence: 99%

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Contaminated Cocaine and Antineutrophil Cytoplasmic Antibody-Associated Disease

McGrath

Isakova

Rennke

et al. 2011

Clinical Journal of the American Society of Nephrology

165

151

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SummaryBackground and objectives Approximately 70% of illicit cocaine consumed in the United States is contaminated with levamisole. Most commonly used as a veterinary antihelminthic agent, levamisole is a known immunomodulating agent. Prolonged use in humans has been associated with cutaneous vasculitis and agranulocytosis. We describe the development of a systemic autoimmune disease associated with antineutrophil cytoplasmic antibodies (ANCA) in cocaine users. This complication appears to be linked to combined cocaine and levamisole exposure. Design, setting, participants, & measurements Cases were identified between March 2009and November 2010 at Massachusetts General Hospital's ANCA laboratory. Cocaine exposure was identified from patient history in all cases. Medical records were reviewed for clinical presentation and for laboratory and diagnostic evaluation.Results Thirty cases of ANCA positivity associated with cocaine ingestion were identified. All had antimyeloperoxidase antibodies and 50% also had antiproteinase 3 antibodies. Complete clinical and laboratory data were available for 18 patients. Arthralgia (83%) and skin lesions (61%) were the most frequent complaints at presentation. Seventy-two percent of patients reported constitutional symptoms, including fever, night sweats, weight loss, or malaise. Four patients had biopsy-proven vasculitis. Two cases of acute kidney injury and three cases of pulmonary hemorrhage occurred. From the entire cohort of 30, two cases were identified during the first 3 months of our study period and nine cases presented during the last 3 months. ConclusionsWe describe an association between the ingestion of levamisole-contaminated cocaine and ANCA-associated systemic autoimmune disease. Our data suggest that this is a potentially life-threatening complication of cocaine use.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Contaminated Cocaine and Antineutrophil Cytoplasmic Antibody-Associated Disease

McGrath

Isakova

Rennke

et al. 2011

Clinical Journal of the American Society of Nephrology

165

151

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“…It has been suggested that cocaine and levamisole act synergistically (22), and that adding levamisole causes increased peripheral sympathetic activity and increased central neurotransmission, enhancing the intense feelings of pleasure produced by the drug. Recent experimental evidence argues against this theory (23).…”

Section: Resultsmentioning

confidence: 99%

Levamisole, Aminorex, and Pulmonary Arterial Hypertension: A Review

Karch¹,

Vaiano²,

Bertol³

2015

Razavi Int J Med

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Context: An epidemic of aminorex-associated pulmonary arterial hypertension (PAH), resulting in multiple fatalities, occurred in the 1970s ending only after the drug was removed from the market. In 2009, when it was found that horses de-wormed with the anthelmintic levamisole, metabolized that drug to aminorex, the same drug that caused the 1970s outbreak of PAH. The discovery would not have been cause for concern except to horseracing enthusiasts, who feared horse doping. However, at about the same time the relationship between levamisole and aminorex was discovered, cocaine cartels began adulterating cocaine with levamisole. The rationale for adulterating cocaine with levamisole remains to be established. The purpose of this short review article is to discuss possible reasons for levamisole contamination, new discoveries about the human pharmacokinetics of aminorex, and the possible relationship between aminorex and pulmonary arterial hypertension in man. Evidence acquisition: Medline contents, as well as estimates published by the U.S. drug enforcement agency (DEA), US state department, and the European monitoring center for drugs and drug abuse (EMCDDA) were reviewed and relevant articles retrieved. There is uniform agreement among the various monitoring agencies analyzed.Results: Approximately 70 percent of the U.S. cocaine supply and 40 percent of the European cocaine supply is contaminated with levamisole. Aminorex has the same binding affinities for serotonin and other neurotransmitters as amphetamine. As serotonin is considered to be an important factor in the development of PAH, the possibility of another epidemic of aminorex-induced PAH, this time among cocaine abusers, seems real, and threatening. Conclusions:The results of the first human pharmacokinetic studies of aminorex were first characterized in 2013. The results suggest that while humans could produce aminorex from levamisole, they probably do not convert very much. Even though cases of PAH have been reported in cocaine users, the latest pharmacokinetic studies suggest that very little aminorex is actually produced from the ingested levamisole, probably not enough to cause PAH. However, since both cocaine and aminorex can cause PAH the situation remains unclear. the lack of a clear answer is partially the development of an insidious pulmonary hypertension, producing subtle and non-specific symptoms in its early stages.

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“…In addition, levamisole has been shown to augment cocaine ' s effects which may explain why use of this harmful adulterant has continued and expanded in recent years. One of many proposed hypotheses is that levamisole may increase peripheral sympathetic activity and central neurotransmission through stimulation of nicotinic acetylcholine receptors thereby augmenting the euphoric effects of cocaine [ 20 ].…”

Section: Levamisole As a Cocaine Adulterantmentioning

confidence: 99%

Bioanalytical methods for quantitation of levamisole, a widespread cocaine adulterant

Shea

2012

Clinical Chemistry and Laboratory Medicine (CCLM)

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Levamisole is an anthelminthic that was first used as a de-worming agent in humans and animals. It has also been used to treat inflammatory conditions as well as certain types of cancer. Levamisole was discontinued for human use in the early 21st century due to toxic side effects including agranulocytosis and vasculitis. Recently, levamisole was discovered as a cocaine adulterant after reports emerged of drug users with the above disorders. As the prevalence of cocaine usage has grown in the last 15 years, measurement of levamisole in human samples has become increasingly important. This review focuses on the various bioanalytical methods available for the determination of levamisole in human plasma and urine. Earlier methods employed gas chromatography coupled with nitrogen-selective thermionic specific detection and nitrogen-phosphorus detection, as well as high performance liquid chromatography coupled with ultraviolet detection. In addition, gas chromatographymass spectrometry (GC-MS) and high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) have also been described. Currently, GC-MS appears to be the method of choice however recent developments in the area of LC-MS/MS make this technology an attractive alternative. The merits of both GC-MS and LC-MS/ MS for the determination of levamisole are evaluated on the basis of sample preparation, chromatographic separation conditions, run time, and analytical performance. In addition, emerging methods in this area are also reviewed.

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The Possible Role of Levamisole in Illicit Cocaine Preparations

Cited by 52 publications

References 0 publications

Contaminated Cocaine and Antineutrophil Cytoplasmic Antibody-Associated Disease

Contaminated Cocaine and Antineutrophil Cytoplasmic Antibody-Associated Disease

Levamisole, Aminorex, and Pulmonary Arterial Hypertension: A Review

Bioanalytical methods for quantitation of levamisole, a widespread cocaine adulterant

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