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Journal of Chemical Neuroanatomy Oct 2017Cocaine is a naturally occurring and illicitly used psychostimulant drug. Cocaine acts at monoaminergic neurotransmitter transporters to block uptake of the monoamines,... (Review)
Review
Cocaine is a naturally occurring and illicitly used psychostimulant drug. Cocaine acts at monoaminergic neurotransmitter transporters to block uptake of the monoamines, dopamine, serotonin and norepinephrine. The resulting increase of monoamines in the extracellular space underlies the positively reinforcing effects that cocaine users seek. In turn, this increase in monoamines underlies the development of addiction, and can also result in a number of severe side effects. Currently, cocaine is one of the most common illicit drugs available on the European market. However, cocaine is increasingly sold in impure forms. This trend is driven by cocaine dealers seeking to increase their profit margin by mixing ("cutting") cocaine with numerous other compounds ("adulterants"). Importantly, these undeclared compounds put cocaine consumers at risk, because consumers are not aware of the additional potential threats to their health. This review describes adulterants that have been identified in cocaine sold on the street market. Their typical pharmacological profile and possible reasons why these compounds can be used as cutting agents will be discussed. Since a subset of these adulterants has been found to exert effects similar to cocaine itself, we will discuss levamisole, the most frequently used cocaine cutting agent today, and its metabolite aminorex.
Topics: Aminorex; Cocaine; Drug Contamination; Humans; Levamisole
PubMed: 28619473
DOI: 10.1016/j.jchemneu.2017.06.001 -
Canadian Medical Association Journal Feb 1979Important contributions that stimulated studies in cancer immunotherapy included: (1) the discovery of tumour-associated antigens; (2) the observation that infection... (Review)
Review
Important contributions that stimulated studies in cancer immunotherapy included: (1) the discovery of tumour-associated antigens; (2) the observation that infection with bacille Calmette-Guérin (BCG) in animals was protective against tumour challenge; and (3) the observation that immunodepression due either to malignant disease or to treatment of the disease, was, in some instances, related to prognosis. Immunotherapy trials with microbial agents have involved attempts to obtain a local effect by injecting the agent into the tumour or into the region of the tumour and to obtain a "systemic" effect distant from the site of injection. Trials with active specific immunotherapy involving tumour cells or tumour cell extracts have frequently involved the combination of these specific agents with a nonspecific adjuvant such as BCG. Recent studies with thymosin and levamisole in patients with lung cancer and other types of malignant disease have shown prolonged survival in the groups receiving immunotherapy.
Topics: Animals; Antigens, Neoplasm; Antineoplastic Agents; BCG Vaccine; Humans; Hypersensitivity, Delayed; Immunotherapy; Leukemia, Lymphoid; Levamisole; Melanoma; Neoplasm Metastasis; Neoplasms; Neoplasms, Experimental; Skin Neoplasms; Thymosin
PubMed: 371776
DOI: No ID Found -
The Journal of Investigative Dermatology Sep 1976Recent advances in our understanding of the pathology and prognosis of malignant melanoma make possible rationally designed immunotherapeutic studies. A number of... (Review)
Review
Recent advances in our understanding of the pathology and prognosis of malignant melanoma make possible rationally designed immunotherapeutic studies. A number of immunologic studies suggest that there may be a specific immune response to melanoma-associated antigens in patients with melanoma; however, other studies have shown lack of specificity, so this issue remains to be definitively resolved. New immunotherapeutic agents, including BCG, TF, and levamisole, among others, offer the potential for improving therapy for patients.
Topics: Antibodies, Neoplasm; Antigens, Neoplasm; BCG Vaccine; Cell Migration Inhibition; Cytotoxicity Tests, Immunologic; Humans; Immunotherapy; Leukocytes; Levamisole; Lymphocytes; Macrophages; Melanoma; Mycobacterium bovis; Skin Tests; Transfer Factor
PubMed: 787436
DOI: 10.1111/1523-1747.ep12514727 -
Archives of Dermatological Research Mar 2023Levamisole exposure in cocaine users is a well-recognized cause of retiform purpura, a distinctive net-like maculopapular patch. Prolonged exposure to levamisole... (Review)
Review
Levamisole exposure in cocaine users is a well-recognized cause of retiform purpura, a distinctive net-like maculopapular patch. Prolonged exposure to levamisole can lead to a serious systemic syndrome known as levamisole-induced vasculitis, most commonly involving the kidneys and lungs. More recently, retiform purpura has been observed in patients with the novel coronavirus disease of 2019 (COVID-19). Due to their overlapping dermatologic and systemic manifestations, levamisole-induced and COVID-19-induced retiform purpura may mimic one another in clinical presentation. The possibility that patients may present with one or both syndromes creates a diagnostic challenge. This review of levamisole-induced and COVID-19-induced retiform purpura highlights their corresponding and distinctive features. Additionally, we propose a unique staging system for levamisole-induced retiform purpura that may be valid for future classification of COVID-19-induced retiform purpura.
Topics: Humans; COVID-19; Levamisole; Purpura
PubMed: 34807290
DOI: 10.1007/s00403-021-02303-1 -
BMJ Clinical Evidence Apr 2008Vitiligo is an acquired skin disorder characterised by white (depigmented) patches in the skin, due to the loss of functioning melanocytes. The extent and distribution... (Review)
Review
INTRODUCTION
Vitiligo is an acquired skin disorder characterised by white (depigmented) patches in the skin, due to the loss of functioning melanocytes. The extent and distribution of vitiligo often changes during the course of a person's lifetime and its progression is unpredictable.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments, and of ultraviolet light treatments, for vitiligo in children and in adults? We searched: Medline, Embase, The Cochrane Library and other important databases up to March 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 25 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: corticosteroids, oral levamisole, topical immunomodulators, topical Vitamin D analogues, ultraviolet A plus psoralen (PUVA), and ultraviolet B (narrowband, and broadband).
Topics: Administration, Oral; Adrenal Cortex Hormones; Humans; Levamisole; Melanocytes; Treatment Outcome; Ultraviolet Therapy; Vitiligo
PubMed: 19450313
DOI: No ID Found -
Molecules (Basel, Switzerland) Nov 2022Helminths, with an estimated 1.5 billion annual global infections, are one of the major health challenges worldwide. The current strategy of the World Health... (Review)
Review
Helminths, with an estimated 1.5 billion annual global infections, are one of the major health challenges worldwide. The current strategy of the World Health Organization to prevent helminth infection includes increasing hygienic awareness, providing better sanitation and preventative anthelmintic drug therapy in vulnerable populations. Nowadays, anthelmintic drugs are used heavily in livestock, both in case of infection and as a preventative measure. However, this has led to the development of resistance against several of the most common drugs, such as levamisole, ivermectin and thiabendazole. As many as 70% of the livestock in developed countries now has helminths that are drug resistant, and multiple resistance is common. Because of this, novel anthelmintics are urgently needed to help combat large-scale production losses. Prior to this review, no comprehensive review of the anthelmintic effects of essential oils and their components existed. Multiple review articles have been published on the uses of a single plant and its extracts that only briefly touch upon their anthelmintic activity. This review aims to provide a detailed overview of essential oils and their components as anthelmintic treatment against a wider variety of helminths.
Topics: Animals; Humans; Oils, Volatile; Anthelmintics; Helminths; Helminthiasis; Levamisole; Drug Resistance
PubMed: 36500419
DOI: 10.3390/molecules27238327 -
Clinical Infectious Diseases : An... Aug 2022Individuals with high microfilarial densities (MFDs) of Loa loa are at risk of developing serious adverse events (SAEs) after ivermectin treatment. Pretreatment with... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Individuals with high microfilarial densities (MFDs) of Loa loa are at risk of developing serious adverse events (SAEs) after ivermectin treatment. Pretreatment with drugs progressively reducing Loa MFDs below the risk threshold might help prevent these SAEs. We assessed the safety and efficacy of levamisole for this purpose.
METHODS
A double-blind, randomized, placebo-controlled, MFD-ascending trial was conducted in the Republic of the Congo. Participants were treated in 3 cohorts defined by pretreatment MFD and levamisole dose (cohort 1: 1.0kg and 1.5mg/kg; cohorts 2 and 3: 2.5mg/kg). Safety outcomes were occurrence of SAE and adverse event frequency during the first week. The efficacy outcomes were MFD reduction from baseline and proportions of individuals with at least 40% and 80% MFD reduction at day 2 (D2), D7, and D30.
RESULTS
The 2 lowest doses (1.0mg/kg and 1.5mg/kg) caused no SAEs but were ineffective. Compared with placebo, 2.5mg/kg levamisole caused more mild adverse events (10/85 vs. 3/85, P=.018), a higher median reduction from baseline to D2 (-12.9% vs. +15.5%, P<.001), D7 (-4.9% vs. +18.7%, P<.001), and D30 (-0.5% vs. +13.5%, P=.036) and a higher percentage of participants with >40% MFD reduction at D2 (17.5% vs. 1.2%, P<.001), D7 (11.8% vs. 6.3%, P=.269), and D30 (18.5% vs. 9.6%, P=.107).
CONCLUSIONS
A single 2.5mg/kg levamisole dose induces a promising transient reduction in Loa loa MFDs and should encourage testing different regimens.
Topics: Animals; Double-Blind Method; Humans; Ivermectin; Levamisole; Loa; Loiasis; Microfilariae
PubMed: 34651190
DOI: 10.1093/cid/ciab906 -
Vascular Pharmacology Jun 2022Levamisole, a veterinary anthelmintic drug, is one of the most widely used and dangerous cocaine adulterants. Like cocaine, levamisole acutely blocks noradrenaline...
Levamisole, a veterinary anthelmintic drug, is one of the most widely used and dangerous cocaine adulterants. Like cocaine, levamisole acutely blocks noradrenaline reuptake but with much less potency, although its vascular effects are not well known. In this study, we evaluated the vascular effects of levamisole and cocaine in rabbit aortic rings used for isometric recording of tension in organ baths and protein expression by western blot. Our results indicated that levamisole (10-10 M) induced a concentration-dependent relaxation in rings precontracted with noradrenaline (10-3 × 10 M). Furthermore, it reduced the contractile response to phenylephrine (10-3 × 10 M) that was not modified by cocaine (10-10 M), and reduced α-adrenergic receptor expression. Levamisole (10-10 M) produced a potentiation of the electrical field stimulation that was not further enhanced by the combination of both drugs. However, high concentrations of levamisole (10 M) abolished adrenergic neurotransmission whether administered alone or with cocaine (10 M). In addition, levamisole (10-10 M) also decreased endothelium-dependent relaxation to acetylcholine that was not further impaired by cocaine (10 M), and that was partially reversed by superoxide dismutase (SOD, 200 U/ml). These results demonstrate that levamisole has a dual effect on the adrenergic system, and its effects are independent of the presence of cocaine. At lower concentrations, it enhances the contractile sympathetic response by blocking presynaptic α-adrenergic receptors, while at high concentrations, the effect of the antagonism of α-adrenergic receptor prevails. In addition, levamisole induces endothelial dysfunction by reducing NO bioavailability, and this effect could be in part mediated by oxidative stress.
Topics: Adrenergic Agents; Animals; Aorta; Cocaine; Levamisole; Norepinephrine; Rabbits; Receptors, Adrenergic, alpha-2
PubMed: 35358704
DOI: 10.1016/j.vph.2022.106992 -
Zeitschrift Fur Rheumatologie Sep 2023Cocaine is a psychotropic tropane alkaloid and stimulant drug. Nasal insufflation of cocaine powder is a common route of administration. In Germany, cocaine is... (Review)
Review
Cocaine is a psychotropic tropane alkaloid and stimulant drug. Nasal insufflation of cocaine powder is a common route of administration. In Germany, cocaine is frequently adulterated with levamisole, an anthelminthic drug with immunomodulatory effects. Both substances are linked to various autoimmune conditions. Cocaine-induced midline destructive lesions cause a progressive destruction of osteocartilaginous structures within the upper respiratory tract and can mimic localized granulomatosis with polyangiitis. In addition, systemic vasculitis due to cocaine and levamisole has been reported. Differentiation of these conditions from primary vasculitis can be challenging because antineutrophil cytoplasmic antibodies (ANCA) are commonly detected. Early diagnosis of these conditions is crucial as clinical improvement is closely related to drug cessation.
Topics: Humans; Cocaine; Levamisole; Cocaine-Related Disorders; Vasculitis; Autoimmune Diseases; Antibodies, Antineutrophil Cytoplasmic
PubMed: 35612660
DOI: 10.1007/s00393-022-01217-1 -
Addiction Biology May 2022Previous brain imaging studies with chronic cocaine users (CU) using diffusion tensor imaging (DTI) mostly focused on fractional anisotropy to investigate white matter...
Previous brain imaging studies with chronic cocaine users (CU) using diffusion tensor imaging (DTI) mostly focused on fractional anisotropy to investigate white matter (WM) integrity. However, a quantitative interpretation of fractional anisotropy (FA) alterations is often impeded by the inherent limitations of the underlying tensor model. A more fine-grained measure of WM alterations could be achieved by measuring fibre density (FD). This study investigates this novel DTI metric comparing 23 chronic CU and 32 healthy subjects. Quantitative hair analysis was used to determine intensity of cocaine and levamisole exposure-a cocaine adulterant with putative WM neurotoxicity. We first assessed the impact of cocaine use, levamisole exposure and alcohol use on group differences in WM integrity. Compared with healthy controls, all models revealed cortical reductions of FA and FD in CU. At the within-patient group level, we found that alcohol use and levamisole exposure exhibited regionally different FA and FD alterations than cocaine use. We found mostly negative correlations of tract-based WM associated with levamisole and weekly alcohol use. Specifically, levamisole exposure was linked with stronger WM reductions in the corpus callosum than alcohol use. Cocaine use duration correlated negatively with FA and FD in some regions. Yet, most of these correlations did not survive a correction for multiple testing. Our results suggest that chronic cocaine use, levamisole exposure and alcohol use were all linked to significant WM impairments in CU. We conclude that FD could be a sensitive marker to detect the impact of the use of multiple substances on WM integrity in cocaine but also other substance use disorders.
Topics: Adult; Anisotropy; Brain; Cocaine; Cocaine-Related Disorders; Diffusion Tensor Imaging; Ethanol; Humans; Levamisole; White Matter
PubMed: 35394690
DOI: 10.1111/adb.13149