Daphnia magna an emerging environmental model of neuro and cardiotoxicity of illicit drugs.

Cocaine, methamphetamine, ectasy (3,4-methylenedioxy amphetamine (MDMA)) and ketamine are among the most consumed drugs worldwide causing cognitive, oxidative stress and cardiovascular problems in humans. Residue levels of these drugs and their transformation products may still enter the aquatic environment, where concentrations up to hundreds of ng/L have been measured. In the present work we tested the hypothesis that psychotropic effects and the mode of action of these drugs in D. magna cognitive, oxidative stress and cardiovascular responses are equivalent to those reported in humans and other vertebrate models. Accordingly we expose D. magna juveniles to pharmacological and environmental relevant concentrations. The study was complemented with the measurement of the main neurotransmitters involved in the known mechanisms of action of these drugs in mammals and physiological relevant amino acids. Behavioural cognitive patters clearly differentiate the 3 psychostimulant drugs (methamphetamine, cocaine, MDMA) from the dissociative one ketamine. Psychostimulant drugs at pharmacological doses (10-200 µM), increased basal locomotion activities and responses to light, and decreased habituation to it. Ketamine only increased habituation to light. The four drugs enhanced the production of reactive oxygen species in a concentration related manner, and at moderate concentrations (10-60 µM) increased heartbeats, diminishing them at high doses (200 µM). In chronic exposures to environmental low concentrations (10-1000 ng/L) the four drugs did not affect any of the behavioural responses measured but methamphetamine and cocaine inhibited reproduction at 10 ng/L. Observed effects on neurotransmitters and related metabolites were in concern with reported responses in mammalian and other vertebrate models: cocaine and MDMA enhanced dopamine and serotonin levels, respectively, methamphetamine and MDMA decreased dopamine and octopamine, and all but MDMA decreased 3 MT levels. Drug effects on the concentration of up to 10 amino acids evidence disruptive effects on neurotransmitter synthesis, the urea cycle, lipid metabolism and cardiac function.

Prenatal cocaine exposure and its influence on pediatric epigenetic clocks and epigenetic scores in humans.

The investigation of the effects of prenatal cocaine exposure (PCE) on offspring has been inconsistent, with few studies investigating biological outcomes in humans. We profiled genome-wide DNA methylation (DNAm) of umbilical cord blood (UCB) from newborns with (n = 35) and without (n = 47) PCE. We used DNAm data to (1) assess pediatric epigenetic clocks at birth and (2) to estimate epigenetic scores (ES) for lifetime disorders. We generated gestational epigenetic age estimates (DNAmGA) based on Knight and Bohlin epigenetic clocks. We also investigated the association between DNAmGA and UCB serum brain-derived neurotrophic factor (BDNF) levels. Considering the large-scale DNAm data availability and existing evidence regarding PCE as a risk for health problems later in life, we generated ES for tobacco smoking, psychosis, autism, diabetes, and obesity. A gene ontology (GO) analysis on the CpGs included in the ES with group differences was performed. PCE was associated with lower DNAmGA in newborns, and this effect remained significant when controlling for potential confounders, such as blood cell type composition predicted by DNAm and obstetric data. DNAmGA was negatively correlated with BDNF levels in the serum of UCB. Higher tobacco smoking, psychosis, and diabetes ES were found in the PCE group. The GO analysis revealed GABAergic synapses as a potential pathway altered by PCE. Our findings of decelerated DNAmGA and ES for adverse phenotypes associated with PCE, suggest that the effects of gestational cocaine exposure on the epigenetic landscape of human newborns are detectable at birth.

The association between neuropsychiatric effects of substance use and occurrence of endoplasmic reticulum and unfolded protein response: A systematic review.

INTRODUCTION: This systematic review aimed to assess the association between neuropsychiatric effects of substance use and occurrence of ER stress and unfolded protein response (UPR) through comprehensive electronic search of existing literature and review of their findings. METHODS: A comprehensive electronic literature search was carried out on research articles published between 1950 to July 2023 through major databases, such as Scopus, Web of Science, Google Scholar, PubMed, PsycINFO, EMBASE, Medline and Cochrane Library. RESULTS: A total of 21 research articles were selected for review, which were comprised of sixteen animal studies, four human studies and one study on postmortem human brain samples. The selected studies revealed that alcohol, methamphetamine, cocaine, opioid and kratom exposures contributed to neuropsychiatric effects: such as decline in learning and memory function, executive dysfunction, alcohol, methamphetamine, opioid, and kratom dependence. These effects were associated with activation and persistent of ER stress and UPR with elevation of BiP and CHOP expression and the direction of ER stress is progressing towards the PERK-eIF2α-ATF4-CHOP pathway and neuronal apoptosis and neurodegeneration at various regions of the brain. In addition, regular kratom use in humans also contributed to elevation of p-JNK expression, denoting progress of ER stress towards the IRE1-ASK1-JNK-p-JNK pathway which was linked to kratom use disorder. However, treatment with certain compounds or biological agents could reverse the activation of ER stress. CONCLUSIONS: The neuropsychiatric effects of alcohol, methamphetamine, cocaine, opioid and kratom use may be associated with persistent ER stress and UPR.

Increased fatty acid synthesis and disturbed lipid metabolism in Neuro2a cells after repeated cocaine exposure: A preliminary study.

Chronic use of cocaine prompts neurodegeneration and neuroinflammation. Lipids play pivotal roles in neuronal function and pathology. Although evidence correlates cocaine use with the alteration of lipid metabolism in blood and brain, the precise mechanism remains to be elucidated. In this study, we explore the effect of cocaine on neuronal fatty acid profiles in vitro. Neuro2a cells following seven days of repeated exposure to cocaine (0, 600, 800, 1000 µM) showed apoptosis-irrelevant cell death, dysregulated autophagy, activation of atypical endoplasmic reticulum stress response, increased saturated and unsaturated fatty acid synthesis, and disrupted lipid metabolism. These preliminary findings indicated the association between lipid metabolism and cocaine-induced neurotoxicity, which should be beneficial for understanding the neurotoxicity of cocaine.

Toxicokinetics of a humanized anti-cocaine monoclonal antibody in male and female rats and lack of cross-reactivity.

A humanized monoclonal antibody h2E2 designed to bind cocaine with high affinity, specificity, and a long half-life (~7 d in rats) is being developed as a treatment for cocaine use disorder. We report here a pharmacokinetic (PK) study of h2E2 using male and female rats conducted under a Good Laboratory Practice (GLP) protocol over a dose range of 40 to 1200 mg/kg. The maximum concentration measured in rat plasma (Cmax) varied proportionately to the dose administered in both male and female rats. The terminal elimination half-lives (t1/2ß) were not significantly different in male and female rats at all doses tested. Importantly, this study reports pharmacokinetics for a humanized monoclonal antibody at a dose never tested before. h2E2 has a high affinity for cocaine, whereas low or no affinity was demonstrated for cocaine metabolites (all except cocaethylene), endogenous monoamines, and methamphetamine. This demonstrates its specificity and a potential lack of interactions with physiological and endocrine systems. A review of the clinical signs in single-dose toxicity studies in rats revealed no effects on the central nervous, respiratory, or cardiovascular systems following single intravenous doses of 40 to 1200 mg/kg. This study predicts that this monoclonal antibody may be safe and effective in humans.

Ephedrine and cocaine cause developmental neurotoxicity and abnormal behavior in zebrafish.

Ephedrine (EPH) and cocaine (COC) are illegal stimulant drugs, and have been frequently detected in aquatic environments. EPH and COC have negative effects on the nervous system and cause abnormal behaviors in mammals and fish at high concentrations, but their mechanisms of neurotoxicity remain unclear in larvae fish at low concentrations. To address this issue, zebrafish embryos were exposed to EPH and COC for 14 days post-fertilization (dpf) at 10, 100, and 1000 ng L-1. The bioaccumulation, development, behavior, cell neurotransmitter levels and apoptosis were detected to investigate the developmental neurotoxicity (DNT) of EPH and COC. The results showed that EPH decreased heart rate, while COC increased heart rate. EPH caused cell apoptosis in the brain by AO staining. In addition, behavior analysis indicated that EPH and COC affected spontaneous movement, touch-response, swimming activity and anxiety-like behaviors. EPH and COC altered the levels of the neurotransmitters dopamine (DA) and γ-aminobutyric acid (GABA) with changes of the transcription of genes related to the DA and GABA pathways. These findings indicated that EPH and COC had noticeable DNT in the early stage of zebrafish at environmentally relevant concentrations.

Subcellular Effectors of Cocaine Cardiotoxicity: All Roads Lead to Mitochondria-A Systematic Review of the Literature.

Cocaine abuse is a serious public health problem as this drug exerts a plethora of functional and histopathological changes that potentially lead to death. Cocaine causes complex multiorgan toxicity, including in the heart where the blockade of the sodium channels causes increased catecholamine levels and alteration in calcium homeostasis, thus inducing an increased oxygen demand. Moreover, there is evidence to suggest that mitochondria alterations play a crucial role in the development of cocaine cardiotoxicity. We performed a systematic review according to the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) scheme to evaluate the mitochondrial mechanisms determining cocaine cardiotoxicity. Among the initial 106 articles from the Pubmed database and the 17 articles identified through citation searching, 14 final relevant studies were extensively reviewed. Thirteen articles included animal models and reported the alteration of specific mitochondria-dependent mechanisms such as reduced energy production, imbalance of membrane potential, increased oxidative stress, and promotion of apoptosis. However, only one study evaluated human cocaine overdose samples and observed the role of cocaine in oxidative stress and the induction of apoptosis though mitochondria. Understanding the complex processes mediated by mitochondria through forensic analysis and experimental models is crucial for identifying potential therapeutic targets to mitigate or reverse cocaine cardiotoxicity in humans.

Near-fatal cocaine intoxication in an infant with thrombotic microangiopathy associated with multiple organ failure.

OBJECTIVE: To report a pediatric case of drug-induced thrombotic microangiopathy caused by cocaine. CASE DESCRIPTION: We report a nine-month-old patient who developed thrombotic microangiopathies after extreme cocaine intoxication, multiple organ dysfunction syndrome with hemodynamic dysfunction, anuric renal failure, liver failure, encephalopathy, and myocardial injury, corresponding phenotypically to thrombocytopenia-associated multiple organ failure. The patient received continuous venous hemofiltration and therapeutic plasma exchange, recovering satisfactorily. She was discharged after 30 days of hospitalization under the guidance of the childcare service, and was healthy after one year of follow-up. Toxicological samples confirmed high levels of cocaine and derivatives in blood, urine and hair. COMMENTS: To our knowledge, this is the first reported pediatric case. There are particularities of cocaine intoxication pathophysiology that can trigger thrombotic microangiopathies because of vasoconstriction, direct endothelial injury, platelet activation, and increasing von Willebrand factor and fibrinogen levels. All of which results in a prothrombotic state, inflammatory dysregulation, and microvascular thrombi. The increasing use of cocaine, especially among young adults, puts children at high risk of toxicity, either by passive unintentional exposure, or abuse due to the increased availability in homes.

Methamphetamine increases force of contraction in isolated human atrial preparations through the release of noradrenaline.

We measured the cardiac contractile effects of the sympathomimetic amphetamine-like drug methamphetamine alone and in the presence of cocaine or propranolol in human atrial preparations. For a more comprehensive analysis, we also examined the effects of methamphetamine in preparations from the left and right atria of mice and, for comparison, analyzed the cardiac effects of amphetamine itself. In human atrial preparations, methamphetamine and amphetamine increased the contractile force, the relaxation rate, and the rate of tension development, and shortened the time to maximum tension and the time to relaxation. Likewise, in mice preparations, methamphetamine and amphetamine increased the contractile force in the left atrium and increased the beating rate in the right atrium. The effect in human atrial preparations started at 1 µM, therefore methamphetamine was less effective and potent than isoproterenol in increasing contractile force. These positive inotropic effects of methamphetamine were greatly attenuated by 10 µM cocaine and abolished by 10 µM propranolol. The inotropic effects of methamphetamine in human atrial preparations were associated with, and are believed to be mediated at least in part by, an increase in the phosphorylation state of the inhibitory subunit of troponin. In conclusion, the sympathomimetic central stimulant drug methamphetamine (as well as amphetamine) increased contractile force and protein phosphorylation, presumably through a release of noradrenaline in isolated human atrial preparations. Thus, methamphetamine acts as an indirect sympathomimetic in the human atrium.

Cocaine induces vascular smooth muscle cells proliferation via DRP1-mediated mitochondrial fission and PI3K/HIF-1α signaling.

Long-term cocaine abuse is associated with cardiovascular and pulmonary vascular complications. The vascular toxicity of cocaine can lead to vascular remodeling characterized by excessive proliferation of vascular smooth muscle cells. Though hypoxia-inducible factor (HIF) signaling and mitochondrial fission have been suggested to play essential roles in the pathogenesis of hypoxia-induced vascular remodeling, pathogenetic mechanism for cocaine-related vascular remodeling remains to be elucidated. In this study, we explore the effect of cocaine on the proliferation of vascular smooth muscle cells by in vitro experiments. The findings indicated that the cocaine-induced vascular smooth muscle cell hyperproliferation is achieved by enhancing DRP1-mediated mitochondrial fission and activating PI3K/HIF-1α signaling. Current findings suggested that mitochondrial fission would play a pivotal role in cocaine-related vascular remodeling and would be helpful in understanding the vascular toxicity of cocaine.

Hot weather and death related to acute cocaine, opioid and amphetamine toxicity in British Columbia, Canada: a time-stratified case-crossover study.

BACKGROUND: Previous research has shown that cocaine-associated deaths occur more frequently in hot weather, which has not been described for other illicit drugs or combinations of drugs. The study objective was to evaluate the relation between temperature and risk of death related to cocaine, opioids and amphetamines in British Columbia, Canada. METHODS: We extracted data on all deaths with cocaine, opioid or amphetamine toxicity recorded as an underlying or contributing cause from BC vital statistics for 1998-2017. We used a time-stratified case-crossover design to estimate the effect of temperature on the risk of death associated with acute drug toxicity during the warmer months (May through September). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for each 10°C increase in the 2-day average maximum temperature at the residential location. RESULTS: We included 4913 deaths in the analyses. A 10°C increase in the 2-day average maximum temperature was associated with an OR of 1.43 (95% CI 1.11-1.86) for deaths with only cocaine toxicity recorded (n = 561), an OR of 1.15 (95% CI 0.99-1.33) for deaths with opioids only (n = 1682) and an OR of 1.11 (95% CI 0.60-2.04) for deaths with amphetamines only (n = 133). There were also elevated effects when toxicity from multiple drugs was recorded. Sensitivity analyses showed differences in the ORs by sex, by climatic region, and when the location of death was used instead of the location of residence. INTERPRETATION: Increasing temperatures were associated with higher odds of death due to drug toxicity, especially for cocaine alone and combined with other drugs. Targeted interventions are necessary to prevent death associated with toxic drug use during hot weather.

Cocaethylene cardiotoxicity in emergency department patients with acute drug overdose.

OBJECTIVES: Cocaine use results in over 500,000 emergency department (ED) visits annually across the United States and ethanol co-ingestion is reported in 34% of these. Commingling cocaine with ethanol results in the metabolite cocaethylene (CE), which is metabolically active for longer than cocaine alone. Current literature on the cardiotoxicity of CE compared to cocaine alone is limited and lacks consensus. This study aims to fill this gap in the literature and examine cardiovascular events in cocaine use as confirmed by urine toxicology versus CE exposure. METHODS: This was a secondary data analysis of a prospective cohort study of adult patients with acute drug overdose at two urban tertiary care hospital EDs over 4 years. Patients with positive urinary cocaine metabolites were analyzed, and outcomes were compared between patients with overdose and confirmed presence of cocaine on urine toxicology (cocaine group) and patients with cocaine and ethanol use (CE group). The primary outcome was cardiac arrest. Secondary outcomes included myocardial injury and hyperlactatemia. Data were analyzed using multivariable regression models. RESULTS: We enrolled a total of 199 patients (150 cocaine, 49 CE). Rates of cardiac arrest were significantly higher in the CE group compared to cocaine (6.1% vs. 0.67%, p = 0.048). Cocaine was significantly associated with myocardial injury compared to CE exposure (mean initial troponin 0.01 ng/ml vs. 0.16 ng/ml, p = 0.021), while hyperlactatemia was associated with CE exposure (mean initial lactate 4.1 mmol/L vs. 2.9 mmol/L, p = 0.038). CONCLUSIONS: When compared to cocaine exposure alone, CE exposure in ED patients with acute drug overdose was significantly associated with higher occurrence of cardiac arrest, higher mean lactate concentrations, and lower occurrence of myocardial injury.

Neurotoxicity Assessment of 1-[(2,3-Dihydro-1-Benzofuran-2-yl)Methyl]Piperazine (LINS01 Series) Derivatives and their Protective Effect on Cocaine-Induced Neurotoxicity Model in SH-SY5Y Cell Culture.

Excessive levels of dopamine in the synaptic cleft, induced by cocaine for example, activates dopaminergic receptors, mainly D1R, D2R, and D3R subtypes, contributing to neurotoxic effects. New synthetic 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazine derivatives (the LINS01 compounds), designed as histaminergic receptor (H3R) ligands, are also dopaminergic receptor ligands, mainly D2R and D3R. This study aims to evaluate the neurotoxicity of these new synthetic LINS01 compounds (LINS01003, LINS01004, LINS01011, and LINS01018), as well as to investigate their protective potential on a cocaine model of dopamine-induced neurotoxicity using SH-SY5Y cell line culture. Neurotoxicity was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), and automated cell counting with fluorescent dyes (acridyl orange and propidium iodide) assays. Concentration-response curves (CRCs) were performed for all LINS compounds and cocaine using MTT assay. The results show that LINS series did not decrease cell viability after 48h of exposure-except for 100 µM LINS01018, which was discontinued from the study. Likewise, MTT, LDH, and fluorescent dyes staining showed no difference is cell viability for LINS compounds at 10 µM. When incubated with 2.5 mM cocaine (lethal concentration 50) for 48h, 10 µM of each LINS compound, metoclopramide (D2R antagonist) and haloperidol (D2R/D3R antagonist), ameliorated cocaine-induced neurotoxicity. However, only metoclopramide, haloperidol, and LINS01011 compound significantly decreased LDH released in the culture medium, suggesting that this new synthetic compound presents a more robust effect. This preliminary in vitro neurotoxicity study suggests that LINS01 compounds are not neurotoxic, and that they play a promising role in preventing cocaine-induced neurotoxicity.

Thymic involution caused by repeated cocaine administration includes apoptotic cell loss followed by ectopic adipogenesis.

Cocaine abuse has a negative impact on the immune system. To investigate the adverse effects of binge cocaine administration on lymphoid organs such as thymus and spleen, we examined the effects of repeated intravenous (i.v.) administration of cocaine on rats. Sprague Dawley rats (male, 8 weeks old) received 20 mg/kg body weight of cocaine hydrochloride per day for 7 or 14 days. In addition to a significant loss in the weight of the spleen, consistent with our previous intraperitoneal (i.p.) injection model of binge cocaine abuse (50 mg/kg cocaine for 7 days), we also found a significant loss of weight as well as apparent shrinkage of the thymus in the cocaine group. Transcriptome analysis of the thymus revealed increased expressions of genes involved in apoptosis, such as Ifi27 and Traf2, as well as decreased expressions of several genes related to lipid metabolism, such as Cd36, Adipoq, Scd1, and Fabp4, in the thymus of the cocaine group (7 days), suggesting an apoptotic loss of thymic cells as well as alterations in lipid metabolism. Paradoxically, cocaine activates PPARγ, a key transcriptional factor activating lipid metabolism, although ectopic adipogenesis was scarcely observed in the thymus. Further analysis of rats administered 20 mg/kg cocaine for 14 days revealed ectopic adipogenesis, which was accompanied with the activation of PPARγ as well as increased expression of Adipoq and Fabp4, in the thymus. Taken together, these results indicate that repeated cocaine administration induces thymic involution, which is initiated by the loss of thymic cells through apoptosis and subsequent ectopic adipocyte development.

Prognosis in substance abuse-related acute toxic leukoencephalopathy: A scoping review.

OBJECTIVES: Abuse of opiates, cocaine, and lipophilic inhalants (e.g., toluene) can damage brain myelin and cause acute toxic leukoencephalopathy (TL), but little is known about recovery or prognosis in this condition. In light of the ongoing opiate epidemic in the United States, it is important to understand the natural history of patients who have acute neurological complications from illicit drug exposure. Our aim was to conduct a scoping review of the literature regarding prognosis in described cases of substance abuse-related TL. METHODS: A strategic search of PubMed, Ovid, Cumulative Index to Nursing, and Allied Health Literature (CINAHL) databases yielded adult cases of acute TL from opiates, cocaine, or inhalants. Cases and case series were eligible for inclusion if they described acute leukoencephalopathy with a clear temporal association with opiate, cocaine, or inhalant abuse. Inclusion was contingent on availability of clinical descriptions until death or ≥ 4 weeks follow-up with neuroimaging consistent with TL. RESULTS: Among 52 cases from 14 articles, 21 (40.4%) individuals died with mean time to death of 28.2 days; with mean follow-up of 12.8 months, 10 (19.2%) survived with no recovery, 17 (32.7%) had partial recovery, and 4 (7.7%) individuals had full recovery. CONCLUSION: Substance abuse-related acute TL often has a poor prognosis, but partial or even full recovery is possible in a subgroup of individuals over months to years.

Differential biochemical and behavioral responses induced by cocaine and benzoylecgonine exposure to the red swamp crayfish Procambarus clarkii.

Cocaine (COC) and its main metabolite, the benzoylecgonine (BE), are the main illicit drugs measured in aquatic system worldwide, with concentrations up to hundreds of ng/L. Although their current environmental concentrations are low these molecules can induce adverse effects at sub-individual level in non-target organisms. In contrast, the information at individual and behavioral level are still scant. The present study aimed at investigating biochemical and behavioral effects induced by 14-days exposure to environmentally relevant concentrations (50 ng/L and 500 ng/L) of COC and BE towards Procambarus clarkii. At sub-individual level, the activity of antioxidant and detoxifying (superoxide dismutase - SOD, catalase - CAT, glutathione peroxidase - GPx and glutathione S-transferases - GST) enzymes, as well as the levels of lipid peroxidation (LPO), were measured as oxidative stress-related endpoints. We also measured the acetylcholinesterase (AChE) activity to check for neurotoxic effect of COC and BE. At individual level, the modulation of some behavioral tasks (i.e., response to external stimuli, changes in feeding activity and exploration of a new environment) were assessed. Although both COC and BE exposure did not induce an oxidative stress situation, a significant inhibition of AChE activity was noted, resulting in behavioral changes in crayfish exposed to COC only. Crayfish exposed to the higher COC concentration showed an increase in the boldness and a decrease in the feeding activity, suggesting that COC may act according to its psychotropic mode of action.

Acute Cardiovascular Toxicity of Cocaine.

Cocaine is one of the most commonly abused drugs and represents a major public health concern. Cocaine users frequently present to the emergency department, with chest pain being the most common presenting complaint. The incidence of acute myocardial infarction in patients with cocaine-associated chest pain is often quoted as 6%, but it is highly variable depending on the included population. Risk assessment can be challenging in these patients; serial assessment of electrocardiograms and troponins is often required. This review focuses on the assessment and management of patients presenting with cocaine-associated chest pain and cardiotoxicity. Specific treatments are discussed, including benzodiazepines, nitroglycerin, calcium channel blockers, and phentolamine, and how treatment priorities differ from patients with noncocaine presentations. The use of beta-blockers in this population remains controversial, and the literature around its use is reviewed. The most recent literature and recommendations for the use of percutaneous coronary intervention and fibrinolytics in cocaine-associated myocardial infarction is discussed as well. Cocaine-associated dysrhythmias are suggested to be the cause of sudden cardiac death in some users. The pathophysiology and evidence-based treatments for dysrhythmias are reviewed. This review provides evidence-based recommendations for the assessment and management of patients presenting with cocaine-associated cardiovascular toxicity.

Methemoglobinemia due to use of poppers: a case report.

BACKGROUND: Methemoglobinemia is an excess of oxidized hemoglobin in the blood, affecting oxygen transportation. It is characterized by central cyanosis that does not respond to oxygen therapy. Prognosis is excellent when treated adequately and rapidly. We present a case report of a 38-year-old Caucasian man suffering from methemoglobinemia due to the use of poppers. CASE PRESENTATION: A 38-year-old Caucasian man known as a smoker and addicted to cocaine was admitted to the emergency department with dyspnea, agitation, and central cyanosis that started approximately 3 hours before admission. The persistent hypoxia despite high-flow oxygen therapy and a history of poppers use helped to reveal a condition known as methemoglobinemia. CONCLUSIONS: Our case highlighted a typical clinical presentation of methemoglobinemia. This possible life-threatening condition can occur after ingestion or inhalation of poppers, commonly sold in sex shops for recreational purposes. This can be easily confirmed by the methemoglobin level of the blood gases, provided the emergency physician considers this diagnosis. Rapid treatment with intravenous methylene blue is effective and leads to a favorable prognosis.

Role of Mitochondrial Dynamics in Cocaine's Neurotoxicity.

The dynamic balance of mitochondrial fission and fusion maintains mitochondrial homeostasis and optimal function. It is indispensable for cells such as neurons, which rely on the finely tuned mitochondria to carry out their normal physiological activities. The potent psychostimulant cocaine impairs mitochondria as one way it exerts its neurotoxicity, wherein the disturbances in mitochondrial dynamics have been suggested to play an essential role. In this review, we summarize the neurotoxicity of cocaine and the role of mitochondrial dynamics in cellular physiology. Subsequently, we introduce current findings that link disturbed neuronal mitochondrial dynamics with cocaine exposure. Finally, the possible role and potential therapeutic value of mitochondrial dynamics in cocaine neurotoxicity are discussed.