Levamisole—a Toxic Adulterant in Illicit Drug Preparations: a Review

Abstract

Discovered in the 1960s, the common anthelminthic levamisole has seen widespread use in veterinary applications. Its use rapidly expanded thereafter to include human medical treatments for a variety of acute and chronic disorders. Because of reports of severe adverse effects, the US Food and Drug Administration withdrew levamisole's approval for human use in 2000; however, medical options outside the United States and illicit options worldwide allow continued accessibility to levamisole. The compound is rapidly metabolized in the body, with at least 2 known active metabolites. Levamisole has a broad range of immunomodulatory effects, including both stimulatory and inhibitory effects on immune responses. It is generally well tolerated at therapeutic concentrations, although a variety of autoimmune-related adverse effects have been reported, including agranulocytosis, leukopenia, purpura, and visible necrotized skin tissue. Individuals with levamisole-compromised immune systems are more susceptible to infections, including COVID-19. Since the early 2000's, levamisole has been frequently used as an adulterating agent in illicit street drugs, especially cocaine, fentanyl, and heroin. Although its prevalence has varied over time and geographically, levamisole has been detected in up to 79% of the street supply of cocaine at levels up to 74% by weight. Its presence in illicit drug markets also raises concern over the potential for exposure of children and neonates, although this is supported by only limited anecdotal evidence. Levamisole is not currently included in routine drug testing panels, although a variety of confirmatory testing techniques exist across a range of antemortem and postmortem specimen options. Because of its varying presence in illicit drug markets, both the medical and forensic communities need to be aware of levamisole and its potential impact on toxicological investigations.

Co‐administration of morphine and levamisole increases death risk, produces neutropenia and modifies antinociception in mice

“…Also, an analysis in lambs reported that a levamisole dose (20 mg/kg) similar to the one used in this study (17.7 mg/kg, i.p.) increased liver enzymes 48 . These findings suggest that longer treatment with levamisole could produce hepatic damage, but this hypothesis requires experimental corroboration.…”

“…increased liver enzymes. 48 These findings suggest that longer treatment with levamisole could produce hepatic damage, but this hypothesis requires experimental corroboration.…”

“…Levamisole has been used as a cocaine adulterant for several years 13,14 and has been recently found in heroin samples 15 . It was marketed as an anthelmintic and immunomodulatory agent but later restricted to veterinary practice because it can cause significant haematological disorders, including agranulocytosis 16–18 .…”

“…12 Levamisole has been used as a cocaine adulterant for several years 13,14 and has been recently found in heroin samples. 15 It was marketed as an anthelmintic and immunomodulatory agent but later restricted to veterinary practice because it can cause significant haematological disorders, including agranulocytosis. [16][17][18] Consistent with this finding, the presence of levamisole in adulterated drugs has been associated with neutropenia, agranulocytosis, retiform purpura and skin necrosis.…”

Towards cross-Canada monitoring of the unregulated street drug supply

“…There is a need to better understand why PWUD use multiple substances in specific patterns given accumulating evidence on risk of harms related to poor physical and mental health [41] and overdose [1,42,43]. Harms may be compounded by adulterants such as levamisole, a non-psychoactive substance found in cocaine or crack that poses risk of multiple serious adverse effects [2,3,44,45].…”