Cognitive and neuroanatomical impairments associated with chronic exposure to levamisole-contaminated cocaine

Abstract

Currently, levamisole is the most common cocaine adulterant worldwide and it is known to induce a variety of adverse side effects. Animal studies and human case reports suggest potential neurotoxicity of the compound but neither neuroanatomical nor cognitive effects of levamisole have been systematically investigated in cocaine users so far. We examined cognitive performance and cortical structural differences between chronic cocaine users with low and high recent exposure to levamisole objectively determined by quantitative toxicological hair analyses. In Study 1, we compared 26 chronic cocaine users with low levamisole exposure (lowLevCU), 49 matched cocaine users with high levamisole exposure (highLevCU), and 78 matched stimulant-naive controls regarding cognitive functioning employing a comprehensive neuropsychological test battery. In Study 2, we investigated cortical thickness by use of T1-weighted MRI in a subgroup of 12 lowLevCU, 17 highLevCU, and 38 stimulant-naive controls. In Study 1, both cocaine user groups showed significant impairments in the cognitive domains of attention and working memory as well as in the global cognitive index. However, highLevCU showed significantly worse executive functions compared to lowLevCU although both groups did not differ in severity of cocaine consumption and other clinical dimensions. Study 2 revealed that highLevCU, displayed reduced cortical thickness specifically in the middle frontal gyrus compared to both controls and lowLevCU. Our results suggest that levamisole exposure during the last months in cocaine users is associated with increased executive function impairments and pronounced thinning of the lateral prefrontal cortex. Consequently, prevention and drug policy-making should aim to reduce levamisole contamination of street cocaine.

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

“…In the present study, we aimed to reanalyze a previously published data set with respect to the long-term neurotoxic effects of levamisole-adulterated cocaine on white matter structures. 25 In a previous study, we showed that cocaine users with a high exposure to levamisole displayed reduced cortical thickness, specifically in the middle frontal gyrus, compared to controls and to cocaine users with low levamisole exposure. 25 In the present study, we also analyzed fluid attenuated inversion recovery (FLAIR) images, which were not reported in the previous study.…”

“…24 However, the dose-dependent effect of levamisole exposure on neurocognitive function and the thinning of distinct cortical areas in human cocaine users has been demonstrated only recently. 25 Although the mode of action of levamisole has yet to be fully elucidated, interaction with nicotinic acetylcholine receptors, stimulation of monoamine transmission and modulation of immune responses have been implicated. 17 Based on existing knowledge of levamisole's action on vessel function, it is likely to contribute to white matter damage in the human brain as well.…”

Longitudinal changes in cocaine intake and cognition are linked to cortical thickness adaptations in cocaine users

“…Finally, we did not control for the potential impact of adulterants such as levamisole. A recent study from our laboratory showed that levamisole-exposure was associated with alterations in fronto-cortical structures of CU ( Vonmoos et al, 2018 ). Unfortunately, in the present study levamisole was not determined in hair at baseline, thus, we were not able to analyze a possible relationship between changes in hair levamisole concentration and GM.…”

Acute Susac Syndrome in a Recent User of Adulterated Cocaine: Levamisole as a Triggering Factor?

“…The Dutch drug monitoring system has observed an increase of up to >70% of cocaine adulterated with levamisole from 2006 to 2014. Levamisole is cheap, has similar physical properties as cocaine, and its metabolite (aminorex) has a longer half-life and amphetamine-like effects that can lengthen the effects of cocaine [6][7][8].…”