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The term \"kratom\" refers to a plant species formally known as  Kratom is composed of over 40 alkaloids, a type of organic compound that contains nitrogen. These compounds work primarily via binding to opioid receptors expressed on neurons, where they stimulate signal transduction mechanisms involving the activation of G proteins. Kratom has been shown to cause both a stimulant-like effect and a sedative effect in humans. These studies have shown that use is highest among European-American, middle-class men living in suburban areas. Additionally, individuals who have a history of opioid misuse are also more likely to take kratom. Kratom is used by many different people in the US for numerous different reasons. Some of the most often cited reasons include treating chronic pain conditions, depression, and anxiety. Individuals who used kratom for these reasons typically consumed kratom daily at a dose of 1-3 grams, with the kratom extracted into a powder to be consumed in a capsule. Additionally, there have been reports of kratom being used to treat opioid withdrawal symptoms, as kratom can bind to some of the same receptors as opioids. This manuscript specifically describes trends regarding the use of kratom in the US, pharmacokinetic and pharmacodynamic properties of kratom, potential therapeutic uses of kratom, adverse events caused by kratom, and case studies in the literature regarding patients using kratom.

Xylazine exacerbates the respiratory depression induced by fentanyl. Because xylazine is a non-opioid, it is resistant to reversal by opioid receptor antagonists such as naloxone (e.g., Narcan ), thereby complicating attempts at treatment of fentanyl overdose. Antagonists of large-conductance potassium BK (big potassium) channels (BK ) in the carotid bodies reverse drug-induced hypoxia (decreased pO ) and hypercapnia (increased pCO ). In animals and human volunteers, the selective BK antagonist ENA-001 reverses the respiratory depression induced by opioids and non-opioids, i.e., it is an \"agnostic\" respiratory reversal agent. Given the seriousness of xylazine plus fentanyl combination (XFC) overdose, the present pilot study in rats was designed to evaluate the potential of a single intravenous bolus of ENA-001 to mitigate the acute respiratory depression induced by a prior intravenous bolus infusion of an XFC. XFC-induced respiratory depression was manifested as a decrease in pO and an increase in pCO . ENA-001, but not the vehicle, rapidly reversed these XFC-induced changes. Based on the results of this pilot study, the \"agnostic\" nature of ENA-001 respiratory stimulation appears to extend to XFC-induced overdose. Given the urgent clinical need, additional study seems warranted.

Although clinical trials demonstrate the superior effectiveness of medication for opioid use disorder (MOUD) compared with nonpharmacologic treatment, national data on the comparative effectiveness of real-world treatment pathways are lacking. To examine associations between opioid use disorder (OUD) treatment pathways and overdose and opioid-related acute care use as proxies for OUD recurrence. This retrospective comparative effectiveness research study assessed deidentified claims from the OptumLabs Data Warehouse from individuals aged 16 years or older with OUD and commercial or Medicare Advantage coverage. Opioid use disorder was identified based on 1 or more inpatient or 2 or more outpatient claims for OUD diagnosis codes within 3 months of each other; 1 or more claims for OUD plus diagnosis codes for opioid-related overdose, injection-related infection, or inpatient detoxification or residential services; or MOUD claims between January 1, 2015, and September 30, 2017. Data analysis was performed from April 1, 2018, to June 30, 2019. One of 6 mutually exclusive treatment pathways, including (1) no treatment, (2) inpatient detoxification or residential services, (3) intensive behavioral health, (4) buprenorphine or methadone, (5) naltrexone, and (6) nonintensive behavioral health. Opioid-related overdose or serious acute care use during 3 and 12 months after initial treatment. A total of 40 885 individuals with OUD (mean [SD] age, 47.73 [17.25] years; 22 172 [54.2%] male; 30 332 [74.2%] white) were identified. For OUD treatment, 24 258 (59.3%) received nonintensive behavioral health, 6455 (15.8%) received inpatient detoxification or residential services, 5123 (12.5%) received MOUD treatment with buprenorphine or methadone, 1970 (4.8%) received intensive behavioral health, and 963 (2.4%) received MOUD treatment with naltrexone. During 3-month follow-up, 707 participants (1.7%) experienced an overdose, and 773 (1.9%) had serious opioid-related acute care use. Only treatment with buprenorphine or methadone was associated with a reduced risk of overdose during 3-month (adjusted hazard ratio [AHR], 0.24; 95% CI, 0.14-0.41) and 12-month (AHR, 0.41; 95% CI, 0.31-0.55) follow-up. Treatment with buprenorphine or methadone was also associated with reduction in serious opioid-related acute care use during 3-month (AHR, 0.68; 95% CI, 0.47-0.99) and 12-month (AHR, 0.74; 95% CI, 0.58-0.95) follow-up. Treatment with buprenorphine or methadone was associated with reductions in overdose and serious opioid-related acute care use compared with other treatments. Strategies to address the underuse of MOUD are needed.

3,4-Methylenedioxymethamphetamine (MDMA), commonly called ecstasy, is a synthetic stimulant popular among young adults. Although its psychoactive effects are sought after, MDMA can lead to serious complications, including neurological and cardiovascular crises. Severe toxicity, although uncommon, may result in cerebral edema, hyponatremia, seizures, or death. We describe the case of a 21-year-old woman who collapsed after taking MDMA and drinking large volumes of water. On arrival at the hospital, she was found to have significant cerebral edema and low sodium. After endotracheal intubation and transfer to a tertiary center, she was managed with intracranial pressure (ICP) monitoring and careful correction of hyponatremia. She made a full recovery and was discharged from intensive care within four days. This report highlights how ICP-guided management can help optimize care and reduce risks in patients with MDMA-related cerebral edema.

Kratom is a partial mu-opioid receptor agonist that has gained popularity as an alternative to opioids for self-treatment of pain, anxiety, and opioid withdrawal. Despite its perceived safety, kratom use is associated with numerous adverse effects, including potentially life-threatening complications. We present the case of a 69-year-old male patient with a history of kratom abuse who developed Hinchey stage IV diverticulitis. Kratom's dose-dependent effects, including gastrointestinal disturbances such as constipation, likely contributed to our patient's condition. Understanding what kratom is, including its uses and potential risks, is essential for physicians to provide informed guidance, recognize kratom-related complications, and ensure patient safety.

We report a case of a 40-year-old male who presented to the emergency department with central cyanosis, altered mental status, and hypoxia that was refractory to supplemental oxygen following ingestion of an alkyl nitrite product called \"Liquid Gold\". Arterial blood gas and co-oximetry confirmed a diagnosis of severe methemoglobinemia with a methemoglobin (MetHb) level in excess of 30%. The patient was treated with intravenous methylene blue and responded quickly both clinically and biochemically. This case further highlights the need to consider the dangers of recreational nitrite toxicity, the pitfalls of standard pulse oximetry in the setting of dyshemoglobinemia, and the value of prompt antidote therapy when faced with toxicological cases.

Opioid use disorder (OUD) is a chronic, relapsing condition with significant health and social consequences. Buprenorphine-naloxone (BUP-NX) and extended-release naltrexone (XR-NTX) are two primary medications used for OUD treatment. A systematic review and meta-analysis were conducted. PubMed, Embase, and Cochrane databases were searched to identify randomized controlled trials (RCTs) comparing BUP-NX and XR-NTX for OUD treatment. Studies were included based on predefined inclusion and exclusion criteria, including patient population, intervention, comparator, outcome measures, and study design. Pooled analyses were performed to assess differences in abstinence time, days of opioid use, negative urine samples, quality of life, and adverse effects. No significant difference was found between BUP-NX and XR-NTX in terms of abstinence time. However, XR-NTX demonstrated a significant advantage in reducing the number of days of opioid use. No significant differences were observed in terms of the number of negative urine samples or quality of life. Adverse effects were comparable between the two treatments. While both medications appear effective for OUD treatment, the choice between BUP-NX and XR-NTX may depend on individual patient factors. Further research is needed to clarify the long-term effects of these medications and to identify optimal treatment strategies for different patient populations.

Methemoglobinemia is an uncommon yet potentially life-threatening condition that results from the oxidation of iron from the ferrous (Fe²⁺) to the ferric (Fe³⁺) state, rendering hemoglobin unable to effectively transport oxygen. This translates into a state of functional hypoxia despite adequate arterial oxygen tension. Among the various causes of acquired methemoglobinemia, recreational inhalation of alkyl nitrites, widely known as \"poppers,\" is a notable but underrecognized trigger. Timely diagnosis and treatment are essential, as the condition can rapidly deteriorate without intervention. We describe the case of a 59-year-old man who presented to the emergency department with collapse, confusion, and prominent central cyanosis following the inhalation of poppers. Interestingly, his pulse oximetry readings were within the normal range, registering between 95 and 98% on room air, which was incongruent with his clinical appearance. This prompted a thorough evaluation, including arterial blood gas analysis, which revealed a markedly elevated methemoglobin level of 29%. Routine blood tests were otherwise unremarkable, and no other contributing toxic exposures were identified. Management involved immediate administration of high-flow supplemental oxygen and intravenous methylene blue at a dose of 1 mg/kg. The patient responded rapidly with the resolution of cyanosis and restoration of normal mental status. Follow-up testing demonstrated a significant decline in methemoglobin levels, and the patient was discharged in full recovery with no residual complications. This case highlights the diagnostic challenges associated with methemoglobinemia, particularly as standard pulse oximetry is unreliable in detecting dyshemoglobinemias and often fails to reflect the true degree of tissue hypoxia. Clinicians should maintain a high index of suspicion when faced with unexplained cyanosis, especially in the context of normal PaO₂ values and possible recreational drug use. Methylene blue remains the gold-standard antidote, functioning as an electron donor that facilitates the reduction of methemoglobin to its oxygen-carrying ferrous state. Early recognition and prompt treatment of methemoglobinemia are vital for preventing serious morbidity or mortality. Moreover, public awareness campaigns addressing the potential toxicological consequences of poppers use are essential to reduce the recurrence of such preventable emergencies. This case underscores the need for emergency physicians and frontline clinicians to consider methemoglobinemia in the differential diagnosis of collapse, unexplained cyanosis, or altered mental status, even when conventional oxygen measurements appear reassuring.

An electrical storm (ES) represents one of cardiology's most formidable and life-threatening crises, marked by relentless ventricular arrhythmias within a 24-hour period. While stimulant cardiotoxicity is an escalating concern, the devastating role of methamphetamine in triggering refractory ES and its deleterious outcomes in advanced cardiomyopathy, particularly within the critical care setting, remains profoundly underreported and poorly understood. We present the urgent case of a 44-year-old male with end-stage dilated cardiomyopathy and chronic, heavy methamphetamine abuse, who spiraled into incessant ventricular tachycardia (VT) storm following acute methamphetamine use. Despite aggressive anti-arrhythmic therapy including over 35 defibrillation shocks, he developed profound cardiogenic shock, intractable arrhythmias, and a rapid progression to multi-organ failure. Maximal support with both extracorporeal membrane oxygenation (ECMO) and intra-aortic balloon pump (IABP) was required, alongside continuous renal replacement therapy (CRRT) for escalating hyperkalemia and renal failure. Despite heroic multidisciplinary efforts, his course was complicated by recurring sepsis and ultimately culminated in progressive multi-organ dysfunction, leading to withdrawal of care on hospital day 16. This critical case study illuminates the therapeutic challenges posed by methamphetamine-induced VT storm in advanced cardiomyopathy. It vividly underscores the imperative for immediate recognition, rapid initiation of a multidisciplinary approach, and aggressive supportive care for such catastrophic arrhythmogenic crises. Furthermore, it highlights the devastating, often irreversible synergy between stimulant cardiotoxicity and structural heart disease, demanding urgent awareness among clinicians to mitigate this growing public health emergency.