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Translational Psychiatry Oct 2018Currently, 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... (Comparative Study)
Comparative Study
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.
Topics: Adult; Antinematodal Agents; Attention; Cerebral Cortex; Cocaine-Related Disorders; Cognitive Dysfunction; Drug Contamination; Executive Function; Female; Humans; Illicit Drugs; Levamisole; Magnetic Resonance Imaging; Male; Memory, Short-Term; Prefrontal Cortex
PubMed: 30368522
DOI: 10.1038/s41398-018-0279-3 -
BMJ Case Reports Aug 2013A 48-year-old woman presented with a red, pruritic and painful skin rash on her legs bilaterally after she snorted cocaine. This was associated with fever and cough....
A 48-year-old woman presented with a red, pruritic and painful skin rash on her legs bilaterally after she snorted cocaine. This was associated with fever and cough. Physical examination showed large violaceous plaques and large flaccid bullae, involving bilateral lower extremities. Blood work showed neutropoenia with absolute neutrophil count of 0.64×10(9) cells/L. Antinuclear antibody, perinuclear antineutrophil cytoplasmic antibody and anti-double-stranded DNA were positive. Biopsy showed thrombogenic vasculopathy which is consistent mainly with levamisole ingestion that was reported with levamisole ingestion. The patient was counselled to stop cocaine misuse and treated with skin emollients and antibiotics for the pneumonia that was discovered on the chest X-ray. Skin ulcers improved and she was discharged in stable condition. Ten days after discharge, she was readmitted with new lesions and worsening necrotic ulcers from the old lesions. The patient admitted to snorting cocaine again a few days after being discharged.
Topics: Cocaine; Cocaine-Related Disorders; Drug Contamination; Female; Humans; Leg Ulcer; Levamisole; Middle Aged; Neutropenia; Recurrence
PubMed: 23997085
DOI: 10.1136/bcr-2013-200507 -
CA: a Cancer Journal For Clinicians 1999Adjuvant therapy, believed by some to be of no benefit for colorectal cancer as recently as 10 years ago, now offers thousands of patients considerable hope after... (Review)
Review
Adjuvant therapy, believed by some to be of no benefit for colorectal cancer as recently as 10 years ago, now offers thousands of patients considerable hope after surgical resection. The first effective adjuvant regimen--combined fluorouracil (5-FU) and levamisole--described in 1989, was soon supplanted by a variety of 5-FU-based regimens, usually combined with leucovorin. Although most recent research in the adjuvant setting has focused on refining chemotherapy doses, schedules, and combinations, with the aim of improving efficacy and decreasing toxicity, investigators have also explored other approaches, such as portal vein infusion, monoclonal antibodies, interferon-alpha, and vaccines. Future directions being evaluated for adjuvant therapy of colon cancer include the use of oral fluorinated pyrimidines, which may replace current intravenous treatments, as well as the incorporation of new agents, such as oxaliplatin and CPT-11, into adjuvant chemotherapy programs.
Topics: Adjuvants, Immunologic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Fluorouracil; Humans; Immunotherapy; Leucovorin; Levamisole
PubMed: 11198882
DOI: 10.3322/canjclin.49.4.202 -
Journal of Women's Health (2002) Sep 2016A growing number of case reports cite serious health complications linked to the cocaine adulterant, levamisole and women are disproportionately affected; however, the...
A growing number of case reports cite serious health complications linked to the cocaine adulterant, levamisole and women are disproportionately affected; however, the clinical effects are not well established. Between April and October of 2010, we conducted a cross-sectional study among 222 homeless and unstably housed women (116 human immunodeficiency virus [HIV]-infected and 106 HIV-uninfected). Immune markers and behavioral factors were compared in separate models by cocaine and levamisole exposure. Overall, 63% of participants were toxicology positive for cocaine/benzoylecgonine, 85% of whom also tested positive for levamisole. Differences in immune markers did not reach levels of significance among HIV-uninfected persons. Compared to HIV-infected persons who were negative for both cocaine and levamisole, the adjusted odds of low white blood cell count were significantly higher among HIV-infected persons positive for both (p = 0.03), but not for those positive for cocaine only. Neutrophil count and HIV viral load did not differ by cocaine and levamisole status among HIV-infected persons. In a separate model, the adjusted odds of testing positive for levamisole were higher among African American women compared to Caucasian and Asian women (p = 0.02). In the context of high levamisole prevalence, results suggest that decreased immune function as a result of levamisole exposure occurs mainly in individuals who are already immune compromised (e.g., HIV-positive), and race/ethnicity appears to be an important factor in understanding levamisole exposure among cocaine-using women. While larger and geographically diverse studies are needed to elucidate these initial findings, results suggest that levamisole may be one mechanism of immune dysfunction in HIV-infected cocaine-using women.
Topics: Adult; Antinematodal Agents; Biomarkers; California; Cocaine; Cocaine-Related Disorders; Cross-Sectional Studies; Drug Contamination; Female; HIV Infections; Ill-Housed Persons; Humans; Levamisole; Logistic Models; Middle Aged; Multivariate Analysis; Self Report
PubMed: 27203838
DOI: 10.1089/jwh.2015.5532 -
Cell Reports Oct 2022Like other pathogens, parasitic helminths can rapidly evolve resistance to drug treatment. Understanding the genetic basis of anthelmintic drug resistance in parasitic...
Like other pathogens, parasitic helminths can rapidly evolve resistance to drug treatment. Understanding the genetic basis of anthelmintic drug resistance in parasitic nematodes is key to tracking its spread and improving the efficacy and sustainability of parasite control. Here, we use an in vivo genetic cross between drug-susceptible and multi-drug-resistant strains of Haemonchus contortus in a natural host-parasite system to simultaneously map resistance loci for the three major classes of anthelmintics. This approach identifies new alleles for resistance to benzimidazoles and levamisole and implicates the transcription factor cky-1 in ivermectin resistance. This gene is within a locus under selection in ivermectin-resistant populations worldwide; expression analyses and functional validation using knockdown experiments support that cky-1 is associated with ivermectin survival. Our work demonstrates the feasibility of high-resolution forward genetics in a parasitic nematode and identifies variants for the development of molecular diagnostics to combat drug resistance in the field.
Topics: Ivermectin; Levamisole; Anthelmintics; Drug Resistance; Benzimidazoles; Genomics; Transcription Factors
PubMed: 36261007
DOI: 10.1016/j.celrep.2022.111522 -
Molecular and Biochemical Parasitology May 2010Cholinergic anthelmintics (like levamisole) are important drugs but resistance with reduced responses by the parasite to these compounds is a concern. There is a need to...
Cholinergic anthelmintics (like levamisole) are important drugs but resistance with reduced responses by the parasite to these compounds is a concern. There is a need to study and understand mechanisms that affect the amplitude of the responses of parasites to these drugs. In this paper, we study interactions of levamisole and ryanodine receptors on contractions of Ascaris suum body muscle flaps. In our second paper, we extend these observations to examine electrophysiological interactions of levamisole, ryanodine receptors (RyRs) and AF2. We report that the maximum force of contraction, g(max), was dependent on the extracellular concentration of calcium but the levamisole EC(50) (0.8 microM) was not. The relationship between maximum force of contraction and extracellular calcium was described by the Michaelis-Menten equation with a K(m) of 1.8mM. Ryanodine inhibited g(max) without effect on EC(50); ryanodine inhibited only 44% of the maximum contraction (K(i) of 40 nM), revealing a ryanodine-insensitive component in the levamisole excitation-contraction pathway. Dantrolene had the same effect as ryanodine but was less potent. The neuropeptide AF2 (1 microM) decreased the levamisole EC(50) to 0.2 microM without effect on g(max); 0.1 microM ryanodine and 100 microM dantrolene, inhibited the g(max) of the AF2-potentiated levamisole response. High concentrations of caffeine, 30 mM, produced weak contraction of the body-flap preparation. Caffeine behaved like ryanodine in that it inhibited the maximum force of contraction, g(max), without effects on the levamisole EC(50). Thus, RyRs play a modulatory role in the levamisole excitation-contraction pathway by affecting the maximum force of contraction without an effect on levamisole EC(50). The levamisole excitation-contraction coupling is graded and has at least two pathways: one sensitive to ryanodine and one not.
Topics: Animals; Anthelmintics; Ascaris suum; Caffeine; Calcium; Cholinergic Agonists; Dantrolene; Furylfuramide; Levamisole; Muscle Contraction; Ryanodine; Ryanodine Receptor Calcium Release Channel
PubMed: 20064566
DOI: 10.1016/j.molbiopara.2009.12.007 -
Clinical Chemistry and Laboratory... Jan 2013Abstract Levamisole is an anthelminthic that was first used as a de-worming agent in humans and animals. It has also been used to treat inflammatory conditions as well... (Review)
Review
Abstract Levamisole is an anthelminthic that was first used as a de-worming agent in humans and animals. It has also been used to treat inflammatory conditions as well as certain types of cancer. Levamisole was discontinued for human use in the early 21st century due to toxic side effects including agranulocytosis and vasculitis. Recently, levamisole was discovered as a cocaine adulterant after reports emerged of drug users with the above disorders. As the prevalence of cocaine usage has grown in the last 15 years, measurement of levamisole in human samples has become increasingly important. This review focuses on the various bioanalytical methods available for the determination of levamisole in human plasma and urine. Earlier methods employed gas chromatography coupled with nitrogen-selective thermionic specific detection and nitrogen-phosphorus detection, as well as high performance liquid chromatography coupled with ultraviolet detection. In addition, gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) have also been described. Currently, GC-MS appears to be the method of choice however recent developments in the area of LC-MS/MS make this technology an attractive alternative. The merits of both GC-MS and LC-MS/MS for the determination of levamisole are evaluated on the basis of sample preparation, chromatographic separation conditions, run time, and analytical performance. In addition, emerging methods in this area are also reviewed.
Topics: Animals; Chromatography, Gas; Chromatography, High Pressure Liquid; Cocaine; Drug Contamination; Humans; Levamisole; Mass Spectrometry
PubMed: 23152411
DOI: 10.1515/cclm-2012-0519 -
Analytical Chemistry Sep 2022Cocaine is one of the most commonly trafficked and abused drugs in the United States, and deployable field tests are important for rapid identification in nonlaboratory...
Cocaine is one of the most commonly trafficked and abused drugs in the United States, and deployable field tests are important for rapid identification in nonlaboratory settings. At present, colorimetric tests exist for in-field determination, but these fundamentally suffer from interferent effects. Cocaine is an organic salt that is readily water soluble as a cation and almost insoluble in the deprotonated neutral form. Here, we take advantage of the electrochemical window of water to increase the pH at the electrode surface by driving water reduction, effectively electroprecipitating the cocaine base. The precipitate on the electrode surface is then electrochemically oxidized by a voltammetric sweep through sufficiently positive potentials. We demonstrate excellent selectivity to cocaine compared to common adulterants, such as procaine, lidocaine, benzocaine, caffeine, and levamisole. Finally, we detect cocaine on a carbon fiber microelectrode, demonstrating miniaturizability and allowing access to low-resistance media (, tap water).
Topics: Benzocaine; Caffeine; Carbon Fiber; Cocaine; Levamisole; Lidocaine; Powders; Procaine; Water
PubMed: 36066582
DOI: 10.1021/acs.analchem.2c01630 -
Archives of Pathology & Laboratory... Aug 2015Levamisole-induced vasculitis is a characteristic cutaneous vasculitis syndrome associated with the use of levamisole-adulterated cocaine. Patients will typically... (Review)
Review
Levamisole-induced vasculitis is a characteristic cutaneous vasculitis syndrome associated with the use of levamisole-adulterated cocaine. Patients will typically present with a painful, purpuric rash in a retiform or stellate pattern with or without central necrosis involving the extremities, trunk, nasal tip, digits, cheeks, and/or ears. A history of cocaine abuse can be elicited. Histologic features include microvascular thrombi and/or leukocytoclastic vasculitis involving small vessels of the superficial and deep dermis. Epidermal involvement is variably seen. Laboratory findings include leukopenia, neutropenia (including agranulocytosis), elevated erythrocyte sedimentation rate, normal coagulation studies, and positive autoantibodies including perinuclear and cytoplasmic antineutrophil cytoplasmic antibodies, antinuclear antibody, and lupus anticoagulant. Differential diagnosis includes other microscopic vasculitides, and clinical and laboratory correlation with histologic findings is essential. Lesions typically resolve with the cessation of cocaine use. Because of the treatment implications and rising incidence of this entity, rapid and accurate diagnosis is essential.
Topics: Adjuvants, Immunologic; Cocaine; Humans; Levamisole; Vasculitis
PubMed: 26230600
DOI: 10.5858/arpa.2014-0107-RS -
Journal of Psychiatry & Neuroscience :... Apr 2021Cocaine use has been associated with vascular pathologies, including cerebral white matter hyperintensities. Street cocaine is most often adulterated with levamisole, an...
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.
Topics: Adult; Cocaine; Cocaine-Related Disorders; Drug Contamination; Female; Humans; Levamisole; Male; White Matter
PubMed: 33844483
DOI: 10.1503/jpn.200057