Adverse effects of levamisole in cocaine users: a review and risk assessment.
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.
Netherlands Institute of Mental Health and Addiction, P.O. Box 725, 3500 AS, Utrecht, The Netherlands. tbrunt@trimbos.nl.
Tibor Markus
TM
Brunt
Netherlands Forensic Institute, P.O. Box 24044, 2490 AA, The Hague, The Netherlands.
Jorrit
J
van den Berg
The Maastricht Forensic Institute, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.
Ed
E
Pennings
Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA, Bilthoven, The Netherlands.
Bastiaan
B
Venhuis
D003042:Cocaine / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics; D019970:Cocaine-Related Disorders / Q000209:etiology* / Q000378:metabolism; D004340:Drug Contamination; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D007978:Levamisole / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics; D015394:Molecular Structure; D018570:Risk Assessment
D007978:Levamisole; D003042:Cocaine
Adverse effects; Agranulocytosis; Cocaine; Levamisole; Neutropenia; Risk assessment; Vasculitis