Methamphetamine Overdose Research Articles

Emergency Room Utilization and Methamphetamine Overdose Symptoms Among Syringe Services Program Participants in Washington State

Background Methamphetamine overdose can cause severe psychological and physical health issues including psychosis, heart attack, and death. People who use methamphetamine (PWUM) who experience methamphetamine overdose symptoms (MOS) are advised to seek emergency healthcare; however, factors related to seeking care are not well characterized. Methods This study used data from the 2021 Washington State Syringe Services Program (SSP) Health Survey, a cross-sectional survey administered to participants at 21 SSPs in Washington (N = 955). Participants answered questions related to substance use including emergency department/room (ER) utilization for methamphetamine use and whether they experienced psychological and physical MOS. Using Poisson regression, we assessed the association between ER utilization for methamphetamine use, non-fatal opioid overdose, and other key covariates among PWUM who experienced MOS. Results Methamphetamine use in the last three months was reported by 86% of participants. Among PWUM, 31% reported psychological MOS, 19% reported physical MOS, and 37% reported ≥1 MOS in the prior three months. Non-fatal opioid overdose (adjusted prevalence ratio [APR] = 2.04, 95% CI = 1.38–3.03), main drug of goofball (heroin and methamphetamine combined) (APR = 1.98, 95% CI = 1.34–2.92) and recent blood infection/sepsis (APR = 2.07, 95% CI = 1.24–3.46) were associated with ER utilization for MOS. Conclusion Among people who use SSPs in Washington State, methamphetamine use remains high, and MOS are common. Recent non-fatal opioid overdose was positively associated with ER utilization for methamphetamine use among PWUM who experienced MOS. Patients in the ER for MOS should be screened for opioid use disorder and linked with harm reduction supplies like naloxone and medications for opioid use disorder.

Methamphetamine Overdose with Acute Kidney Injury and Rhabdomyolysis

Methamphetamine Overdose with Acute Kidney Injury and Rhabdomyolysis

The intersection of methamphetamine and violence in the United States: a county-level assessment of methamphetamine overdose mortality and violent crime

ABSTRACT Objective This study sought to investigate the correlation between community methamphetamine use, gauged by overdose mortality rates, and incidence of violent crime. Method We carried out a descriptive, cross-sectional analysis of county-level data from multiple public sources, involving all 3147 US counties. Methamphetamine overdose rates for the year 2019 were derived from CDC WONDER, while violent crime rates were collected from NIBRS. Results Our data set contained 522 counties with complete information, largely metro (92.72%). Overdose data was suppressed for 2625 counties—697 (26.55%) metro, and 1928 (73.45%) non-metro, hence multiple imputation was utilized for comprehensive results. The analysis showed significant correlations between methamphetamine overdose and all violent crime, and specifically robbery (F = 5.55, P = .005 and F = 47.60, P <.001, respectively). Conclusion Our study suggests that communities with higher methamphetamine overdoses likely face increased rates of crime, specifically robbery, which could impact costs associated with law enforcement, prosecution, and healthcare. The study offers valuable insights for law enforcement and policymakers, and underlines the need for further research to fully understand the dynamics of methamphetamine use and violence at the community level.

Liver damage in a mouse model of methamphetamine overdose.

Currently, the incidence of death due to methamphetamine (METH) overdose is increasing rapidly in the US. Liver damage is a consequence of METH overdose. Our objective was to produce acute METH-induced hepatotoxicity observable by the clinical serum biomarker alanine aminotransferase (ALT).&#x0D; In this study, 9 week old male CD-1 IGS mice (n=6-7/group) were administered 0 (saline), 10, or 20 mg/kg intraperitoneal (ip) METH every 2 hours for a total of 4 doses. One day after the first METH dose, mice were weighed and 30 minutes of spontaneous locomotor activity was measured. Immediately afterward, serum was collected for the determination of ALT.&#x0D; Both the 10 and 20 mg/kg METH regimens increased animal stress as measured by a significant reduction in spontaneous locomotor activity and weight loss (p&lt;.05), but there were no significant differences between the two doses. While the 10 mg/kg regimen did not produce any significant elevations in ALT compared to saline control, the 20 mg/kg METH regimen significantly increased ALT compared to both saline and the 10 mg/kg METH regimen (p&lt;.05).&#x0D; In conclusion, this 20 mg/kg METH overdose regimen produced acute hepatotoxicity in mice. It will be used in the future development of pharmacotherapies protective against METH-induced liver damage.

\u201cIt\u2019s called overamping\u201d: experiences of overdose among people who use methamphetamine

BackgroundThe USA is experiencing increases in methamphetamine use and methamphetamine-related or attributed deaths. In the current study, we explore qualitative narratives of methamphetamine overdose and strategies used by people who use drugs to reduce the undesirable effects associated with methamphetamine use.MethodsWe conducted 21 qualitative interviews with people over the age of 18 who reported using methamphetamine in the previous 3 months in Nevada and New Mexico. Interviews were recorded, transcribed, and analyzed using qualitative thematic analysis.ResultsRespondents described a constellation of psychological and physical symptoms that they characterized as “overamping,” experienced on a continuum from less to more severe. Reports of acute, fatal methamphetamine overdose were rare. Few reported seeking medical attention for undesirable effects (usually related to psychological effects). General self-care strategies such as sleeping and staying hydrated were discussed.ConclusionsWhen asked directly, our respondents claimed that acute, fatal methamphetamine overdose is rare or even impossible. However, they described a number of undesirable symptoms associated with overconsumption of methamphetamine and had few clinical or harm reduction strategies at their disposal. Addressing this current wave of drug-related deaths will require attention to the multiple factors that structure experiences of methamphetamine “overdose,” and a collaborative effort with PWUDs to devise effective harm reduction and treatment strategies.

Naltrexone-Bupropion Combination May Reduce Methamphetamine Use

Naltrexone-Bupropion Combination May Reduce Methamphetamine Use

Methamphetamine Overdose Deaths in the US by Sex and Race and Ethnicity

This cross-sectional study examines the extent to which methamphetamine overdose deaths vary by sex and race and ethnicity in the US.

Opioid, Cocaine and Methamphetamine Overdose Crisis and Deaths in 2021

Opioid, Cocaine and Methamphetamine Overdose Crisis and Deaths in 2021

M100907 and BD 1047 attenuate the acute toxic effects of methamphetamine

There are no Food and Drug Administration approved pharmacotherapies for methamphetamine (METH) overdose, thus identifying novel drug targets to prevent this devastating adverse event is a public-health imperative. Previous research suggests that serotonin and sigma receptors may contribute to the adverse effects of METH. The present study assessed whether pretreatment with the 5-HT2A receptor antagonist M100907 or the sigma 1 (σ1) receptor antagonist BD 1047 attenuated METH-induced lethality, hyperthermia, convulsions, and seizures. Male, Swiss-Webster mice received intraperitoneal injections of M100907 (1 and 10 mg/kg), BD 1047 (10 mg/kg), or a combination of M100907 (1 mg/kg) and BD 1047 (10 mg/kg) prior to treatment with METH (78 mg/kg). Convulsions and lethality were assessed by observation, core body temperature was assessed by surgically implanted telemetric probes, and seizures were assessed by electroencephalography. M100907 reduced METH-elicited lethality from 67% to 33%, BD1047 reduced METH-elicited lethality from 67% to 50%, and combined administration of both agents eliminated lethality in all mice tested. Similarly, both agents and their combination reduced METH-elicited seizures and convulsions. None of the treatments decreased METH-induced hyperthermia. This research suggests that reducing METH-induced seizures is an important factor in reducing lethality associated with METH overdose. However, future studies should examine whether M100907 and BD 1047 modulate METH-induced hypertension and other adverse effects that may also contribute to METH overdose. Our data support the continued investigation of compounds that target 5-HT2A and σ1 receptors in METH-induced overdose, including their potential to yield emergency reversal agents.

Serotonin 2A and Sigma 1 Receptor Antagonists Synergize to Block the Acute Toxicity of Methamphetamine

Currently there are no Food and Drug Administration approved pharmacotherapies for methamphetamine (METH) overdose, thus identifying novel drug targets to prevent this devastating adverse event is a public‐health imperative. Previous research suggests that serotonin and sigma receptors may contribute to the adverse effects of METH.Determine whether antagonism of serotonin 2A (5‐HT2A) and sigma 1 (σ1) alone or in combination attenuates METH‐induced lethality, hyperthermia, convulsions, and seizures.Male, Swiss Webster mice received intraperitoneal injections of the selective 5‐HT2A receptor antagonist M100907 (1–10 mg/kg), the selective σ1 receptor antagonist BD 1047 (10–30 mg/kg), and a combination of M100907/BD 1047 (1:10 mg/kg) prior to treatment with METH (78 mg/kg ‐ LD67). Convulsions and lethality were assessed by observation, core body temperature was assessed by surgically implanted telemetric probes, and seizures were assessed by electroencephalography.M100907 and BD 1047 administered alone had no significant effect on METH‐induced lethality. However, combined antagonism of 5‐HT2A and σ1 receptors eliminated lethality in all mice tested (a reduction from LD67 to LD0). Similarly, only the combination of 5‐HT2A and σ1 receptor antagonism eliminated seizure activity. All three treatments decreased tonic‐clonic convulsions as measured on a modified Racine scale. None of the treatments decreased METH‐induced hyperthermia.This research suggests that reducing METH‐induced seizures may be critical for reducing METH‐induced lethality. These data support the continued investigation of the role of 5‐HT2A and σ1 receptors in METH overdose, including their potential to yield emergency reversal agents.Support or Funding InformationThese studies were supported by the National Institutes on Drug Abuse [NS100512] and by funding from the Mercer University College of Pharmacy (Murnane KS‐ Principal Investigator; Canal CE– Principal Investigator)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Leakage of the blood-brain barrier followed by vasogenic edema as the ultimate cause of death induced by acute methamphetamine overdose.

Methamphetamine (METH) is a potent CNS stimulant that is widely used as a recreational drug. Due to its ability to increase bodily heat production and diminish heat loss due to peripheral vasoconstriction, METH is able to increase brain and body temperature. The hyperthermic effects of METH are potentiated when the drug is used under conditions of psycho-physiological activation and in warm ambient temperatures. In this short review, we present and discuss our data on the effects of METH on brain temperature and a number of neural parameters that characterize permeability of the blood-brain barrier (albumin immunoreactivity), glial activity (GFAP immunoreactivity), brain tissue water content, and structural abnormalities of brain cells. We demonstrate that the extent of these neural alterations strongly depends on METH-induced brain temperature elevation and they all dramatically increase following exposure to METH in warm (29°C) vs. standard (23°C) ambient temperatures. Based on these data we consider possible pathophysiological mechanisms underlying acute METH toxicity, suggesting the critical role of drug-induced brain hyperthermia, temperature-dependent leakage of the blood-brain barrier (BBB), and the development of vasogenic edema that could finally result in decompensation of vital functions and death.

Brain Histamine N-Methyltransferase as a Possible Target of Treatment for Methamphetamine Overdose

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Effects of acute and chronic systemic methamphetamine on respiratory, cardiovascular and metabolic function, and cardiorespiratory reflexes.

Methamphetamine (METH) abuse is escalating worldwide, with the most common cause of death resulting from cardiovascular failure and hyperthermia; however, the underlying physiological mechanisms are poorly understood. Systemic administration of METH in anaesthetised rats reduced the effectiveness of some protective cardiorespiratory reflexes, increased central respiratory activity independently of metabolic function, and increased heart rate, metabolism and respiration in a pattern indicating that non-shivering thermogenesis contributes to the well-described hyperthermia. In animals that showed METH-induced behavioural sensitisation following chronic METH treatment, no changes were evident in baseline cardiovascular, respiratory and metabolic measures and the METH-evoked effects in these parameters were similar to those seen in saline-treated or drug naïve animals. Physiological effects evoked by METH were retained but were neither facilitated nor depressed following chronic treatment with METH. These data highlight and identify potential mechanisms for targeted intervention in patients vulnerable to METH overdose. Methamphetamine (METH) is known to promote cardiovascular failure or life-threatening hyperthermia; however, there is still limited understanding of the mechanisms responsible for evoking the physiological changes. In this study, we systematically determined the effects on both autonomic and respiratory outflows, as well as reflex function, following acute and repeated administration of METH, which enhances behavioural responses. Arterial pressure, heart rate, phrenic nerve discharge amplitude and frequency, lumbar and splanchnic sympathetic nerve discharge, interscapular brown adipose tissue and core temperatures, and expired CO2 were measured in urethane-anaesthetised male Sprague-Dawley rats. Novel findings include potent increases in central inspiratory drive and frequency that are not dependent on METH-evoked increases in expired CO2 levels. Increases in non-shivering thermogenesis correlate with well-described increases in body temperature and heart rate. Unexpectedly, METH evoked minor effects on both sympathetic outflows and mean arterial pressure. METH modified cardiorespiratory reflex function in response to hypoxia, hypercapnia and baroreceptor unloading. Chronically METH-treated rats failed to exhibit changes in baseline sympathetic, cardiovascular, respiratory and metabolic parameters. The tonic and reflex cardiovascular, respiratory and metabolic responses to METH challenge were similar to those seen in saline-treated and drug naive animals. Overall, these findings describe independent and compound associations between physiological systems evoked by METH and serve to highlight that a single dose of METH can significantly impact basic homeostatic systems and protective functions. These effects of METH persist even following chronic METH treatment.

Brain Histamine N-Methyltransferase As a Possible Target of Treatment for Methamphetamine Overdose.

Stereotypical behaviors induced by methamphetamine (METH) overdose are one of the overt symptoms of METH abuse, which can be easily assessed in animal models. Currently, there is no successful treatment for METH overdose. There is increasing evidence that elevated levels of brain histamine can attenuate METH-induced behavioral abnormalities, which might therefore constitute a novel therapeutic treatment for METH abuse and METH overdose. In mammals, histamine N-methyltransferase (HMT) is the sole enzyme responsible for degrading histamine in the brain. Metoprine, one of the most potent HMT inhibitors, can cross the blood–brain barrier and increase brain histamine levels by inhibiting HMT. Consequently, this compound can be a candidate for a prototype of drugs for the treatment of METH overdose.

Pretreatment or Posttreatment with Aripiprazole Attenuates Methamphetamine-induced Stereotyped Behavior in Mice

Aripiprazole is a third-generation atypical antipsychotic and a dopamine D2 receptor partial agonist. In the present study, we investigated whether a single administration of aripiprazole to mice, either as a pretreatment or as a posttreatment, would affect stereotypy induced by methamphetamine (METH). Pretreatment of male ICR mice with aripiprazole (1 or 10 mg/kg, i.p.) attenuated the incidence of METH-induced stereotypical behavior in a dose-dependent manner. Pretreatment of mice with 1 mg/kg aripiprazole produced an increase in the locomotor activity in mice treated with METH compared with mice treated with vehicle plus METH and with 10 mg/kg aripiprazole plus METH. This increase in locomotion is indicative of a rightward shift in the dose–response curve for METH, consistent with a shift in the type of stereotypical behavior observed from biting to sniffing. Aripiprazole posttreatment, after METH-induced stereotypical behavior, was fully expressed and also significantly attenuated overall stereotypy in an aripiprazole dose-dependent manner. These data suggest that the antagonism of METH effects by aripiprazole should be investigated as a potential treatment for acute METH overdose.

Development of a GC–MS method for methamphetamine detection in Calliphora vomitoria L. (Diptera: Calliphoridae)

Entomotoxicology is the study of using insects for the detection of drugs and other chemical substances in decomposing tissues. One research aspect in particular is the effects of these substances on arthropod development and morphology, and their consequences on the post mortem interval estimation. Since methamphetamine (MA) is becoming commonplace as an illegal recreational drug, a GC–MS method for the detection of MA in Calliphora vomitoria L. (Diptera: Calliphoridae) was developed and validated. Furthermore, the effect of MA on the development, growth rates and survival of the blowfly was investigated. Larvae were reared on liver substrates homogeneously spiked with measured amounts of MA (5ng/g and 10ng/g) based on typical concentrations found in human tissue in cases of death caused by MA overdose. The experimental results demonstrated that (i) MA produced a significant increase in the developmental time from egg to adult in C. vomitoria, (ii) approximately 60% of larvae exposed to either dose of MA died during the pupation period and (iii) the resultant lengths of larvae and pupae were on average significantly larger than the controls.

Gender Difference in the Characteristics among Unintentional Methamphetamine Overdose Patients Referring to Poison Center-an Epidemiologic Survey

Background : Despite a significant increase in the number of persons using Methamphetamine, limited data exist concerning demographic characteristics non-fatal meth ”Shisha” overdoses, seeking for treatment. Methods: Gender differences in socio-demographic characteristics, drug use record and self-harm behaviors related to Methamphetamine “Shisha” overdose were examined among 263 patients (189males, 74 females) admitted to poison center, Loghman hospital. Results: Of the 263 methamphetamine “Shisha” overdose included in this study, 189 (71.9%) were Male and 74 (28.1%) were female with mean of age of 34 years and standard deviation of 12.8. Male “Shisha” users were more likely to be married, middle school educated, and self-employed. History of drug abuse was positive in 73.5% mainly in male. “Shisha” was the main drug used by 24.6% male and 23.1% female subjects. Inhalation was main rout in 174 (66.2%) of cases. Conclusion: There may be gender difference in the characteristics of participants with “Shisha” overdose. The findings suggest that interventional programs are necessary for specific risk reduction strategies.

Sigma receptor antagonists attenuate acute methamphetamine-induced hyperthermia by a mechanism independent of IL-1β mRNA expression in the hypothalamus

Methamphetamine is currently one of the most widely abused drugs worldwide, with hyperthermia being a leading cause of death in methamphetamine overdose situations. Methamphetamine-induced hyperthermia involves a variety of cellular mechanisms, including increases in hypothalamic interleukin-1 beta (IL-1β) expression. Methamphetamine also interacts with sigma receptors and previous studies have shown that sigma receptor antagonists mitigate many of the behavioral and physiological effects of methamphetamine, including hyperthermia. The purpose of the current study was to determine if the attenuation of methamphetamine-induced hyperthermia by the sigma receptor antagonists, AZ66 and SN79, is associated with a concomitant attenuation of IL-1β mRNA expression, particularly in the hypothalamus. Methamphetamine produced dose- and time-dependent increases in core body temperature and IL-1β mRNA expression in the hypothalamus, striatum, and cortex in male, Swiss Webster mice. Pretreatment with the sigma receptor antagonists, AZ66 and SN79, significantly attenuated methamphetamine-induced hyperthermia, but further potentiated IL-1β mRNA in the mouse hypothalamus when compared to animals treated with methamphetamine alone. These findings suggest sigma receptor antagonists attenuate methamphetamine-induced hyperthermia through a different mechanism from that involved in the modulation of hypothalamic IL-1β mRNA expression.

Monoclonal antibodies for treating methamphetamine overdose and addiction

Monoclonal antibodies for treating methamphetamine overdose and addiction

A single high dose of methamphetamine increases cocaine self-administration by depletion of striatal dopamine in rats

Psychostimulant addicts often take high doses of drugs, and high doses of psychostimulants such as methamphetamine (METH) are neurotoxic to striatal dopamine (DA) terminals. Yet, the effects of high doses of METH on drug-seeking and drug-taking behavior have not been examined. In the present study, we found that single high doses of METH in rats (10–20 mg/kg) dose-dependently increased cocaine self-administration under fixed-ratio 2 (FR2) reinforcement conditions, while higher doses (40 mg/kg×1 or 10 mg/kg/2 h×4) caused high mortality among rats maintained on daily cocaine self-administration. The increased cocaine self-administration appeared to be a compensatory response to reduced cocaine reward after METH, because the same doses of METH caused a dose-dependent reduction both in “break-point” levels for cocaine self-administration under progressive-ratio reinforcement and in nucleus accumbens DA response to acute cocaine. Further, METH (10–20 mg/kg) produced large DA release (4000%–6000% over baseline), followed by a significant reduction in striatal DA and 3,4-dihydroxyphenylacetic acid (DOPAC) contents, but without significant changes in striatal DA transporter levels. These findings suggest that the present high doses of METH caused striatal DA depletion or hypofunction without severe damage in DA terminals, which may contribute to the increased cocaine-taking behavior observed in the present study. Provided that the present doses of METH may mimic METH overdose incidents in humans, the present findings suggest that METH-induced DA depletion or neurotoxicity may lead to an increase in subsequent drug-taking and drug-seeking behavior.