Use of levamisole-adulterated cocaine is associated with increased load of white matter lesions

Abstract

Background: Cocaine use has been associated with vascular pathologies, including cerebral white matter hyperintensities. Street cocaine is most often adulterated with levamisole, an anthelminthic drug that may also be associated with vascular toxicity. However, whether levamisole exposure from cocaine consumption further accelerates the development of white matter lesions remains unknown. Methods: We investigated the association of cocaine and levamisole exposure with white matter hyperintensities in 35 chronic cocaine users and 34 healthy controls. We measured cocaine and levamisole concentrations in hair samples, which reflected exposure up to 6 months previously. We assessed the number and total surface area of the white matter hyperintensities using structural MRI (FLAIR sequence). Using generalized linear models, we analyzed the contributions of cocaine and levamisole to the number and area of white matter hyperintensities, accounting for several confounding factors. Results: Analysis using generalized linear models revealed that cocaine users had more white matter hyperintensities in terms of total surface area, but not in terms of number. Further generalized linear models that included cocaine and levamisole hair concentrations (instead of group) as predictors indicated that levamisole exposure was strongly associated with more and larger white matter hyperintensities, suggesting that the elevated white matter hyperintensities in cocaine users were driven mainly by levamisole exposure. Finally, white matter hyperintensities in levamisole-exposed cocaine users were located primarily in the periventricular and juxtacortical white matter. Limitations: The sample size was moderate, and blood pressure was not systematically assessed. Conclusion: As an adulterant of cocaine, levamisole appears to increase the risk of white matter injury.

A longitudinal investigation of blood neurofilament light chain levels in chronic cocaine users

“…Contrary to our expectations, NfL was not associated with the concentration of the adulterant levamisole, which has been linked to structural brain alterations in CU. 10,11,23,24 The findings of previous studies by our group suggested that levamisole induces thinning of the prefrontal cortex and increases white matter pathology. 10,11 However, in the current sample, the concentration of levamisole in hair was relatively low compared to our previous studies, which is in line with the observed reduction of levamisole concentration in cocaine samples in Switzerland during the recruitment period.…”

“…10,11,23,24 The findings of previous studies by our group suggested that levamisole induces thinning of the prefrontal cortex and increases white matter pathology. 10,11 However, in the current sample, the concentration of levamisole in hair was relatively low compared to our previous studies, which is in line with the observed reduction of levamisole concentration in cocaine samples in Switzerland during the recruitment period. 10 Similarly, we found no link between NfL levels and depressive symptoms, history of childhood trauma, or ADHD symptoms.…”

“…Thus, the extent to which these structural impairments are directly related to cocaine-induced brain pathology (neurotoxicity) rather than preexisting traits (predisposition) remains unclear. 8,9 Moreover, cocaine adulteration with neurotoxic compounds (e.g., the anthelmintic levamisole), 10,11 concomitant use of other illicit substances or alcohol, 12 and comorbidity with psychiatric disorders (e.g., depression) 12-15 might influence brain integrity in chronic cocaine users (CU) independently of cocaine intake itself. Considering the limitations of current diagnostic methods, which are mostly limited to cost-intensive neuroimaging measures, the introduction of new markers of active brain pathology may help clarify crucial questions on substance-induced brain pathology and provide new monitoring tools for physicians working in addiction medicine.…”

“…7,21,22 Finally, we expected that levamisole (a common adulterant of cocaine) would have an additional impact on NfL levels, given its proven neurotoxic effects on white and gray matter. 10,11,23,24…”

Assessment of FDA-approved drugs against Strongyloides ratti in vitro and in vivo to identify potentially active drugs against strongyloidiasis

“…The drug is misused as an adulterant and cutting agent in cocaine distribution [ 16 ]. Levamisole-adulterated cocaine use has been reported to cause severe adverse events including neutropenia and agranulocytosis, vasculitis, skin necrosis, and arthralgia, which resulted in withdrawal of levamisole as a human drug [ 17 ]. The drug was, however, found safe and well tolerated in the doses used as an anthelmintic in human clinical trials [ 18 ] and is still listed on the WHO list of essential list of medicines as anthelmintic ( https://list.essentialmeds.org/ ).…”