Levamisole as an adulterant in a cocaine overdose fatality

The deceased, a previously well woman in her early 20s, was found dead in circumstances suspicious of a drug overdose. The death was reported to the coroner and the autopsy findings were unremarkable, with no evidence of injury or significant natural disease processes.

Toxicological sampling of blood revealed a cocaine level in the blood of 4.9 mg/L, as well as the cocaine metabolite benzoylecgonine at a level of 3.4 mg/L. These are lethal levels for cocaine and benzoylecgonine.1 Cocaine was also detected in a nasal swab, and levamisole was detected in the nasal swab and in the blood, as well as in a quantity of white powder found near the woman’s body. The cause of death was given as cocaine toxicity.

Illicit cocaine in Australia is generally diluted (“cut”) with a range of innocuous substances, including fructose and sucrose, and less commonly with other drugs, such as lignocaine.2 In this case, levamisole was detected as a contaminant. Levamisole is primarily used as a veterinary anthelmintic, and used uncommonly in humans for rheumatoid arthritis, and as adjuvant therapy to fluorouracil in the treatment of a variety of cancers.3,4 Agranulocytosis is a significant side effect of levamisole, and this has limited its use in humans. The clinical presentation of agranulocytosis is protean, presenting with a spectrum of abnormalities, ranging from a flu-like illness to leukopenia with a potentially fatal outcome.3-5 The mechanism whereby levamisole induces agranulocytosis is unknown, although a strong link with the human leukocyte antigen HLA-B27 and rheumatoid factor positivity suggests a likely genetic predisposition.4

Recent reports from the United States and Canada have highlighted the presence of levamisole in seized illicit cocaine entering these countries, with up to 69% of seized cocaine lots containing levamisole. There has been a subsequent clustering of fatal and nonfatal cases of agranulocytosis in a number of disparate locations.3-5 The reason for contaminating cocaine with levamisole is unknown, although there are indications that levamisole may promote the effects of cocaine by interfering with its reuptake at a synaptic level.4

Although there was no evidence of agranulocytosis in the present case, we highlight the apparent recent appearance of this contaminant in the cocaine supply in Australia, because it has the potential to induce reversible agranulocytosis in people not otherwise obviously at risk for this condition.