Archives of Toxicology

, Volume 91, Issue 6, pp 2303–2313 | Cite as

Adverse effects of levamisole in cocaine users: a review and risk assessment

  • Tibor Markus BruntEmail author
  • Jorrit van den Berg
  • Ed Pennings
  • Bastiaan Venhuis
Review Article


The immunomodulatory adjuvant and antihelminth levamisole is increasingly used as an adulterant in cocaine worldwide. An accumulating body of clinical and toxicological literature has appeared since 2010 describing neutropenia, agranulocytosis, leukoencephalopathy and vasculitis in cases associated with levamisole-adulterated cocaine. Mostly, neutropenia and agranulocytosis were reported, characterized by a decimation of neutrophils. A large proportion of cases also involved vasculopathy, characterized by pronounced black and purple skin purpura with cutaneous necrosis. Females are more susceptible for both agranulocytosis and vasculitis. Another complication reported with levamisole-adulterated cocaine is leukoencephalopathy, a disabling and potentially fatal neurological disorder caused by cerebral demyelination. In this review, all adverse effects associated with therapeutic levamisole and levamisole-adulterated cocaine are described. In addition, this review provides an update of the pharmacology of levamisole, its metabolism, including toxic metabolites and metabolites that are relevant for levamisole’s addition to cocaine. Special emphasis is put on the immunopathology and the dose–effect relationship of chronic levamisole exposure. Finally, a risk assessment is provided based on the current level of levamisole adulteration in street cocaine, the dose range calculated per gram and the pattern of chronic exposure in heavy or dependent users.


Levamisole Cocaine Adverse effects Agranulocytosis Vasculitis Neutropenia Risk assessment 


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Tibor Markus Brunt
    • 1
    Email author
  • Jorrit van den Berg
    • 2
  • Ed Pennings
    • 3
  • Bastiaan Venhuis
    • 4
  1. 1.Netherlands Institute of Mental Health and AddictionUtrechtThe Netherlands
  2. 2.Netherlands Forensic InstituteThe HagueThe Netherlands
  3. 3.The Maastricht Forensic InstituteMaastrichtThe Netherlands
  4. 4.Laboratory for Health Protection ResearchNational Institute for Public Health and the Environment (RIVM)BilthovenThe Netherlands

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