Midlife and Older Age Methamphetamine Poisoning Deaths in Hawai'i.

Unintentional and undetermined intent drug overdose fatality records from the State Unintentional Drug Overdose Reporting System (SUDORS) for Hawai'i from July 1, 2020, to December 31, 2021 revealed that 58.2% of decedents were aged 50-75. The main substance associated with cause of death for those aged 50-75 years was methamphetamine, followed by a combination of mixed drugs. Of those aged 50 and older, 25.5% died from cardiovascular or neurological complications which were likely to be associated with chronic, long-term methamphetamine use. Based on death investigator narrative reports, 76.5% of the older decedents had a history of substance abuse, suggesting possible long-term substance use starting at a young age. The trajectory of substance use over the life course is often influenced by life events and transitions, which can be stressors. Hawai'i kupuna (older adults) should be screened for substance use and dependence to ensure that there is treatment if needed, for the entirety of this use trajectory.Also, barriers to kupuna seeking treatment, such as stigma towards drug use should be addressed.

Systematic review protocol to determine the most effective pharmacological and non-pharmacological interventions for the management of acute methamphetamine toxicity.

INTRODUCTION: This study describes the protocol for a systematic review. The systematic review will address experiences of managing methamphetamine intoxication, specifically violence and agitation related to intoxication, in the emergency department (ED). METHODS AND ANALYSIS: This study uses the Grading of Recommendations Assessment, Development and Evaluation system to guide the methods in this section. The primary objective of the review is to identify experimental studies assessing the effectiveness of both pharmacological and non-pharmacological strategies to manage acute methamphetamine intoxication in patients presenting violently in the ED. Our secondary objectives will be to assess the impact of specific strategies on the time it takes to achieve de-escalation and/or sedation, the length of stay in the ED, frequency of admission, mortality and provider satisfaction with the intervention. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Conjoint Health Research Ethics Board REB21-1387. Results will be published in a peer-reviewed journal and presented at healthcare conferences in Canada. TRIAL REGISTRATION NUMBER: The protocol is registered through the International Prospective Register of Systematic Reviews (identification number: CRD42020157938) and will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extensions for systematic review protocols.

Cardiotoxicity After Synthetic Cathinone Use; Two Cases, A Case Series and Scoping Review.

The cardiotoxic effects of synthetic cathinones remain largely unknown. In this study, we present two cases, a case series and a scoping review, to explore synthetic cathinone associated cardiotoxicity. Case 1 involved a 28-year-old male with non-ST-elevation myocardial infarction after ingesting a substance containing 4-methylmethcathinone (4-MMC), 3-methylmethcathinon (3-MMC), and methcathinone. Case 2 involved a 49-year-old male with ventricular fibrillation after 4-methylmethcathinone ingestion, who was diagnosed with severe three-vessel disease. A retrospective analysis was performed on self-reported synthetic cathinone poisonings reported to the Dutch Poisons Information Centre from 2012 to 2022. A total of 222 mono-intoxications with cardiotoxicity were included, mostly involving 3-methylmethcathinon (63%). Often tachycardia, hypertension, palpitations, and chest pain were reported. A comprehensive literature search was performed on PubMed to identify the studies reporting cardiac arrest, myocardial infarction, cardiac inflammation, cardiomyopathy, and life-threatening arrhythmias following synthetic cathinone use. A total of 30 articles reporting 40 cases were included. The reported complications included cardiac arrest (n = 28), ventricular tachycardia (n = 4), supraventricular tachycardia (n = 1), ST-elevation myocardial infarction (n = 2), non-ST-elevation myocardial infarction (n = 2), cardiomyopathy (n = 1), and myocarditis (n = 2). A total of ten different associated synthetic cathinones were identified. Cardiac arrest, myocardial infarction, and ventricular arrhythmias have been reported following the use of synthetic cathinones, underscoring the importance of obtaining a detailed recreational drug use history from patients presenting with syncope, chest pain, or palpitations.

Amphetamine-type drug-related fatalities in the context of 8 years of methamphetamine use measured by wastewater analysis in South Australia.

Methamphetamine is the illicit stimulant of choice in Australia. Countless initiatives have been employed to reduce methamphetamine use and drug-related harm. Wastewater analysis (WWA) has been used effectively as an objective measure of drug use at a population level and can be compared to indicators of harm, such as the number of drug-related fatalities. This paper attempts to describe methamphetamine use in the context of changes in levels measured in wastewater in South Australia whilst recognising considerable interventions over an 8-year period. Validated liquid chromatography-mass spectrometry methods were used to determine methamphetamine (and MDMA) levels in wastewater over an 8-year interval. The number of drug-induced deaths and driver fatalities involving methamphetamine (and MDMA) was presented and described in the context of changes in use measured by WWA. A rise in methamphetamine use according to WWA was evident up to 2017, followed by a gradual decrease to 2020 back to 2015 levels. Both driver fatalities and drug-induced deaths correlated well with use measured by WWA over the 8-year period. Multiple initiatives to curb supply, distribution and harm within the state and nationally have been implemented. The decrease in methamphetamine use after 2017 suggests that timely interventions have successfully reduced overall drug use and has led to fewer fatalities. This study shows that the response to increasing methamphetamine use in South Australia has resulted in a reversal of the upward trend in consumption and fewer drug-related fatalities.

Fire deaths in Cape Town, South Africa: A retrospective review of medico-legal and toxicological findings (2006 - 2018).

BACKGROUND: In South Africa, fire-related deaths are common, particularly within dense informal housing settlements. Published data on deaths from fire incidents in Cape Town is sparse. Additionally, little emphasis has been placed on the role of toxicological investigations in these deaths, despite the known risk of alcohol and drug impairment to burn injury. METHODS: A retrospective, descriptive analysis of post-mortem case reports from Salt River Mortuary was conducted to investigate all deaths in which fires were involved in the west metropole of Cape Town, between 2006 to 2018. Demographic, circumstantial, and toxicological data were analyzed using R software. RESULTS: In total 1370 fire deaths occurred over 13 years, with a mean of 106 (SD ± 18) cases per annum (≈3% of the annual caseload and a mortality rate of 5.5 per 100,000). Males (70.4%), adults (mean=30.7 years), and toddlers (1-4 years old) were notably at risk. Deaths typically occurred in the early morning (00h00 - 06h00) (45.7%), during winter (32.1%), and in lower socioeconomic areas with highly dense informal settlements (65.6%), with 29% of deaths occurring in multi-fatality incidents. Ethanol was detected (≥0.01 g/100 mL) in 55.1% of cases submitted for analysis (71.5%), with a mean of 0.18 g/100 mL, and with 93.8% of positive cases > 0.05 g/100 mL. Carboxyhaemoglobin (COHb) analysis was requested in 76.4% of cases, with 57% of cases having a %COHb of ≥ 20%. Toxicology results (for drugs other than ethanol) from the national laboratory were outstanding in 34.4% of the cases at the conclusion of the study. BAC and %COHb were significantly higher in deaths from burns and smoke inhalation (usually accidents) than deaths from combined trauma and burns (typically homicides). Fire deaths with high COHb levels were more likely to display cherry-red discoloration (OR=3.1) and soot in the airways (OR=2.7) at autopsy. CONCLUSION: This article provides an updated description of fire deaths in the west metropole of Cape Town. The importance of BAC and COHb testing in these cases was noted, and the authors call for an investigation of the role of drug impairment (specifically frequently misused drugs methamphetamine and methaqualone) as a risk factor in these deaths. Areas of high-density informal settlements, where open flames are used to heat, light, and cook, were noted as high risk.

Inpatient Complications and Outcomes for Burn Patients Admitted With Methamphetamine Intoxication.

Methamphetamine intoxication frequently complicates inpatient burn admissions. While single-institution studies describe adverse outcomes during resuscitation, little is known about the risks of amphetamine intoxication on inpatient complications and perioperative management. The US National Trauma Data Bank was queried for burn encounters between 2017 and 2021. Amphetamine intoxication was identified on admission. Primary outcomes included death, stroke, and myocardial infarction (MI). Secondary outcomes included organ failure and surgical management. Multivariable regressions modeled outcomes adjusting for available covariates including demographics, TBSA burned, and inhalation injury. Bonferroni adjustments were applied. Our study identified a total of 73,968 primary burn encounters with toxicology screens. Among these, 800 cases (1.1%) were found to have positive methamphetamine drug screens upon admission. Methamphetamine users were significantly older (41.7 vs 34.9 years, P < .001), had a greater percentage of males (69.6 vs 65.4, P = .045), were more likely to have inhalation injury (P < .001), and had larger %TBSA burns (16% vs 13%, P < .001). Methamphetamine users were no more likely to die, experience MI, or experience stroke during admission. In contrast, methamphetamine users were significantly more likely to have alcohol withdrawal (P = .019), acute kidney injury (AKI) (P < .001), deep vein thrombosis (P = .001), pulmonary embolism (PE) (P = .039), sepsis (P = .026), and longer intensive care unit (ICU) stays (P < .001). Methamphetamine use was associated with a longer number of days to the first procedure (P = .005). Of all patients who required surgery (15.0%), methamphetamine users required significantly more total debridements and reconstructive procedures (P < .001). While not associated with mortality, methamphetamine intoxication was associated with an increased risk of many complications including PE, deep vein thrombosis, AKI, sepsis, and longer ICU stays. Methamphetamine intoxication was associated with delays in surgical care.

The motives and methods of methamphetamine and 'heroin' co-use in West Virginia.

BACKGROUND: Opioid and methamphetamine co-use is increasing across the USA with overdoses involving these drugs also rising. West Virginia (WV) has led the US in opioid overdose death rates since at least 2013 and rising co-use of methamphetamine with opioids has played a greater role in deaths over the last 5 years. METHODS: This study used rapid ethnography to examine methods and motivations behind opioids and methamphetamine co-use from the viewpoint of their consumers. Participants (n = 30) were people who injected heroin/fentanyl also using methamphetamine who participated in semi-structured interviews. RESULTS: We found multiple methods of co-using opioids and methamphetamine, whether alternately or simultaneously and in varying order. Most prioritized opioids, with motives for using methamphetamine forming three thematic categories: 'intrinsic use', encompassing both inherent pleasure of combined use greater than using both drugs separately or for self-medication of particular conditions; 'opioid assisting use' in which methamphetamine helped people manage their existing heroin/fentanyl use; and 'reluctant or indifferent use' for social participation, reflecting methamphetamine's low cost and easy availability. CONCLUSIONS: Methamphetamine serves multiple functions among people using opioids in WV. Beliefs persist that methamphetamine can play a role in preventing and reversing opioid overdose, including some arguments for sequential use being protective of overdose. 'Reluctant' uptake attests to methamphetamine's social use and the influence of supply. The impact on overdose risk of the many varied co-use patterns needs further investigation.

Methamphetamine-related forensic autopsy cases in a Japanese prefecture over a 7-year period: Characteristics of deaths and blood concentrations.

Understanding the actual conditions of methamphetamine (MA)-related death is important from the perspectives of criminal justice and public health. In this report, we review 104 cases of MA-related death handled by our departments between January 2014 and December 2020. Based on information from police and autopsy examinations, we classified the cases into the following categories: "accidental intoxication" ("MA only" and "multiple drugs or alcohol"), "fatal disease" ("definitively MA-related," "possibly MA-related," and "unlikely MA-related"), "accident," "suicide," "homicide," and "undetermined." The total number and annual trends for each category and their respective femoral blood concentrations were investigated. "Fatal disease" was the most common category (48 cases), followed by "suicide" (25 cases), "accidental intoxication" (14 cases), and "accident" (11 cases). "Definitively MA-related" in which MA may have played a role in their onset or exacerbation accounted for the majority of "fatal disease": 12 cases of heart disease, 4 cases of aortic dissection, 12 cases of cerebral hemorrhage, and 4 cases of subarachnoid hemorrhage. Cases classified as "definitively MA-related" died with lower femoral blood concentrations of MA compared with "MA only." Cases with "fatal disease" might have been misdiagnosed as "death by natural causes" if a proper autopsy and toxicology examinations were not performed. In death investigations, it is necessary to keep in mind that there are some MA-related deaths, and efforts should be made to increase awareness about the risk of death in using this drug.

The rise of illicit fentanyls, stimulants and the fourth wave of the opioid overdose crisis.

PURPOSE OF REVIEW: This review provides an update on recently published literature on the rise of illicit fentanyls, risks for overdose, combinations with other substances, e.g. stimulants, consequences, and treatment. RECENT FINDINGS: Overdose due to illicit synthetic opioids (e.g. fentanyl and fentanyl analogs) continues to rise in the US both preceding and during the COVID-19 pandemic. Fentanyl-related overdose is rising in new geographic areas e.g. the western USA. Stimulant-related overdose is also increasing nationwide driven by methamphetamine and cocaine. Polysubstance use, e.g. the use of a stimulant along with an opioid is driving stimulant-related overdose. Other medical consequences of injection drug use are rising including HIV and hepatitis C infections. Medication approaches to treating opioid use disorder remain the standard of care and there are new promising pharmacological approaches to treating methamphetamine use disorder. SUMMARY: A 'fourth wave' of high mortality involving methamphetamine and cocaine use has been gathering force in the USA. Availability and use of illicit fentanyls are still the major drivers of overdose deaths and the current rise in stimulant-related deaths appears entwined with the ongoing opioid epidemic.

Methamphetamine-related postmortem cases in Jeddah, Saudi Arabia.

A more than 500% increase in the number of deaths involving methamphetamine occurred between 2016 and 2018 in Jeddah, Saudi Arabia. As such, this report employed a validated liquid chromatography tandem mass spectrometry method to quantify methamphetamine and its metabolites in bodily fluids from 47 postmortem cases in which methamphetamine was involved. The mean age of the deceased was 33 years old (median: 30, range: 16-63), and 94% were male. Methamphetamine was co-ingested with another drug in 32 of the cases (68%); however, the deaths were only due to the combined toxicity of methamphetamine and another drug in 15 of the cases (32%). Of note, 13 of these deaths (28% of all deaths) involved heroin. When methamphetamine was the sole cause of death (32% of the studied cases), the median concentrations of methamphetamine and amphetamine were 527 and 128 ng/mL. When methamphetamine was combined toxicity with another drug, the median concentrations of methamphetamine and amphetamine decreased to 161 and 53 ng/mL. When deaths were unrelated to methamphetamine, the median concentrations of methamphetamine and amphetamine were 130 and 44 ng/mL, respectively. The highest median methamphetamine concentration was found in urine (5281 ng/mL), followed by stomach contents (878 ng/mL), bile (762 ng/mL), vitreous humor (3 ng/mL), and blood (208 ng/mL). Almost 40% of the studied cases involved violence, 61% were accidental, 21% were suicides, 17% were homicides, and 2% were natural deaths. Methamphetamine is highly addictive. Increases in deaths have been seen in various countries. More awareness, education and treatment programs are required to reduce the likelihood of addiction, crimes, suicide, and other fatalities resulting from methamphetamine abuse.

Methamphetamine exposures reported to United States poison control centers, 2000-2019.

OBJECTIVE: To investigate characteristics and trends of methamphetamine exposures reported to United States (US) poison control centers. METHODS: Data from the National Poison Data System were analyzed. RESULTS: From January 1, 2000 through December 31, 2019, US poison control centers managed 54,199 cases involving methamphetamine as the first-ranked substance. Adults 20-39 years old accounted for more than half (56.3%) of cases. There were 1,291 deaths, of which 43.0% involved multiple-substance exposures. Among multiple-substance exposures in which methamphetamine was the first-ranked substance, stimulants and street drugs (excluding methamphetamine) were most commonly also present (22.7%), followed by opioids (19.0%). The substance class associated with the most fatalities was opioids (n = 243, 26.6%). The rate of methamphetamine exposures per 100,000 US population increased from 0.6 to 1.1 from 2000-2005, then decreased from 1.1 to 0.4 from 2005-2007, followed by an increase from 0.4 to 2.6 from 2007-2019. From 2007-2019, the rate significantly increased in all US regions, and among all age groups, except among 6-12-year-olds. Also, the rates of single-substance and multiple-substance exposures each increased significantly (both p < 0.0001) from 2007-2019, as did the overall methamphetamine fatality rate per 100,000 US population (0.0036 to 0.022, p < 0.0001). From 2000-2019, the proportions of cases resulting in admission to a health care facility and serious medical outcome increased from 30.2% to 47.8% (p < 0.0001) and from 37.6% to 54.0% (p < 0.0001), respectively. CONCLUSIONS: The rate of exposure to methamphetamine in the US declined initially following passage of the Combat Methamphetamine Epidemic Act of 2005. However, since 2007, the rate and severity of exposures to methamphetamine have increased, primarily driven by individuals 20 years or older. Increased prevention efforts are needed, including prevention of methamphetamine initiation among adolescents and young adults, improved access to effective treatment for co-occurring mental health and substance use disorders, and prevention of unintentional exposures among children.

Methamphetamine-associated pulseless electrical activity in a young child.

This is a case report of a 19-month-old female who presented to the emergency department in cardiac arrest after methamphetamine exposure. Prior to presentation, she had seizure-like activity and then became unresponsive. On arrival, she had dilated pupils, intermittent clonus, and pulseless electrical activity. She was found to have full thickness circumferential burns of her bilateral lower extremities. She received 12 doses of epinephrine, cardiopulmonary resuscitation, and volume resuscitation after which she had return of spontaneous circulation and was transferred to the intensive care unit on an epinephrine drip. Initial laboratory studies showed a mixed metabolic and respiratory acidosis and hyperglycemia. An initial urine immunoassay for drugs of abuse was negative, however, 5 h later, a second urine immunoassay was positive for amphetamine. The first specimen was also sent for liquid chromatography-mass spectrometry analysis that later returned positive for methamphetamine and amphetamine. In retrospect, the initial urine screen was found to have evidence of amphetamine below the threshold for positivity (500 ng/mL), and the second urine specimen was highly positive, with an amphetamine level of >1450 ng/mL. In this case, what turned out to be a sub-threshold rather than undetectable level was clinically significant, highlighting the challenges of urine screening in cases of suspected poisoning syndromes with atypical presentations. Our case also suggests the possibility of PEA as a presentation of methamphetamine toxicity in a child.

Stimulant storm - state health department psychostimulant age-adjusted mortality rate correlates with psychostimulant-based Michigan Poison Center case exposures over time.

BACKGROUND: Deaths attributable to psychostimulants with abuse potential have increased in the United States (US) in recent years. Methamphetamine use, in particular, has risen sharply. We evaluated the correlation between amphetamine- and methamphetamine-related case exposures reported to the Michigan Poison Center (MiPC) coinciding with psychostimulant age-adjusted mortality rates from the Michigan Department of Health and Human Services (MDHHS). METHODS: We compared amphetamine and methamphetamine exposures reported to the MiPC from 2012 to 2018, queried from ToxSentry® database, to MDHHS reports on resident death certificates with attributed death due to "overdose, regardless of intent" and related cause of death attributed to psychostimulants with abuse potential. Linear regression assessed goodness-of-fit. Slope with standard error and adjusted R2 were reported. Psychostimulants included methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), dextroamphetamine, levoamphetamine, and methylphenidate. RESULTS: Psychostimulant deaths reported by MDHHS increased from 17 to 165 between 2012 and 2018. The average age-adjusted rate of psychostimulant-involved overdose deaths per 100,000 state residents rose from 0.2 to 1.8. Linear regression of MiPC amphetamine exposure rates with state health department-reported age-adjusted psychostimulant mortality rates yielded a slope of 1.93, SE 0.5, p value 0.035, and adjusted R2 0.55. Linear regression of MiPC methamphetamine exposure rates with state health department-reported age-adjusted psychostimulant mortality rates yielded a slope of 0.78, SE 0.27, p value 0.012, and adjusted R2 0.70 suggesting a strong correlation. CONCLUSION: Psychostimulant use and associated deaths in the US are increasing, representing an evolving public health threat. Michigan demonstrates consistency with national trends and data from the MiPC correlates strongly with state-reported age-adjusted psychostimulant mortality rates. Strengthening collaboration between poison centers and state health departments is critical for detection and mitigation efforts and can thereby inform resource allocation.

Non -fatal overdose among people who inject drugs in Tehran, Iran.

BACKGROUND: With increasing frequencies of non-fatal overdose in people who inject drugs (PWID), it is essential to improve our knowledge about associated risk factors for overdose to inform overdose prevention and assistance programs. The aim of present study was to determine the prevalence of non-fatal overdose and the associated risk factors among PWID in Tehran, Iran. METHODS: Snowball sampling was used to collect data from 465 participants in Tehran using a cross-sectional survey. Consenting participants who reported drug injecting in the past month and were able to speak and comprehend Farsi enough to respond to survey questions were interviewed. The endpoint of interest was non-fatal overdose in the previous 6 months, or answering "Yes" to the question: "In the last six months, have you ever overdosed by accident? (at least once)". We used STATA v. 14 for this analysis. Statistical significance was defined as p < 0.05 for all analyses. RESULTS: Of 465 PWIDs who participated in this study, all were male, and about half had less than a high school education. The prevalence of self-reported non-fatal overdose in the past 6 months was 38% (CI95%: 34, 43%). Our findings indicate that characteristics and behaviors that were associated with an increased risk of experiencing an overdose in the past 6 months were drug use initiation under 22 years (AOR =2.2, P < 0.05), using methamphetamine (AOR =2.8, P < 0.05), and using multiple drugs at the same time (AOR =2.1, P < 0.05). Also, more recent initiates to injecting (< 2 years) had an increased risk of experiencing an overdose in the past 6 months. The odds of experiencing a non-fatal overdose among PWIDs who regularly attended NSP were 0.6 times less than for those who did not attend regularly (OR = 0.6,95% CI: 0.2-0.9). CONCLUSION: Methamphetamine and alcohol use were the most significant association for non-fatal overdose among PWIDs. Our results indicate that intervention and prevention initiatives seeking to reduce overdoses among PWIDs should not only be focused on the primary drug used but also the use of alcohol and poly-drug use.

Fatal hemorrhage complicated with methamphetamine poisoning and its post-mortem CT features.

The purpose of this study was to assess the incidence of fatal hemorrhage complicated with methamphetamine (MA) poisoning and to examine the postmortem computed tomography (PMCT) features of fatal intracerebral hemorrhage (ICH) with and without MA poisoning. The study also attempted to determine the differences in PMCT between those two groups. Consecutive medicolegal autopsy data from November 2011 to February 2018 were searched for 3044 cases. First, the incidence and distribution of all cases of nontraumatic fatal hemorrhage with various causes were examined. Second, cases of ICH on the basal ganglia and brain stem were extracted. The PMCT findings were compared with respect to nine parameters: volume of hematoma, ventricular perforation, midline shift distance, aortic calcification, calcification of aortic valve, calcification of coronary artery, cardiothoracic ratio, circumference of ascending aorta, and volume of bladder contents. Of the 3044 cases, 97 were nontraumatic fatal hemorrhage; of these 97 cases, 20 were classified as MA poisoning with 9 ICH cases, and 60 cases were classified as non-MA poisoning with 14 ICH cases. A statistically significant difference in ages was observed between the two groups. On PMCT comparison of ICH, statistically significant differences were evident in the midline shift distance and calcification of the aortic valve. Forensic radiologists should be aware of the possibility of ICH with MA poisoning if fatal hemorrhage is detected on PMCT. Younger age, less calcification of the aortic valve, and a remarkable midline shift may be the keys to recognition.

Accidental Overdose Deaths in Oklahoma, 2002-2017: Opioid and Methamphetamine Trends.

To evaluate trends related to accidental overdose deaths in Oklahoma, with a focus on opioids and methamphetamine. All accidental drug overdose deaths in the state of Oklahoma from 2002 to 2017 were reviewed. Opioids were grouped into the following categories: all opioids, prescription opioids, synthetic opioids and heroin. Age-adjusted death rates for methamphetamine and each opioid category were calculated and analyzed. Accidental overdoses accounted for 9,936 deaths during the study period. Of these, opioids were seen in 62.9%, with prescription opioids comprising 53.8%, synthetic opioids 10.3% and heroin 2.8%. Synthetic opioids, despite a recent upward nationwide trend, showed a slight overall decrease (-6.8%) from 2009 to 2017. In contrast, methamphetamine showed a 402.2% increase from 2009 to 2017 and an overall increase of 1,526.7%. Methamphetamine was involved in the most overdoses (1,963), followed by oxycodone (1,724). Opioid-related deaths were most common among white individuals (90.3%) and showed a slight male predilection (56.9%). With the intent of assessing the opioid epidemic as it relates to accidental overdoses in Oklahoma, this study suggests that opioid-related overdoses have slowed in recent years amidst a sharp increase in methamphetamine deaths.

LC3 and ATG5 overexpression and neuronal cell death in the prefrontal cortex of postmortem chronic methamphetamine users.

Methamphetamine (METH) abuse is accompanied by oxidative stress, METH-induced neurotoxicity, and apoptosis. Oxidative stress has devastating effects on the structure of proteins and cells. Autophagy is an evolutionarily conserved intracellular regulated mechanism for orderly degradation of dysfunctional proteins or removing damaged organelles. The precise role of autophagy in oxidative stress-induced apoptosis of dopaminergic neuronal cells caused by METH has not clarified completely. In this study, we sought to evaluate the effects of METH abuse on autophagy in the prefrontal cortex of postmortem users, mainly focusing on the ATG5 and LC3 during neuroinflammation. Postmortem molecular and histological examination was done for two groups containing 12 non-addicted and 14 METH addicted cases. ATG5 and LC3 expression were analyzed by real-time PCR and immunohistochemistry (IHC) methods. Histopathological analysis was performed by stereological cell counting of neuronal cells using Hematoxylin and Eosin (H & E) staining technique. In order to detect DNA damage in the prefrontal lobe, Tunnel staining was performed. Real-time PCR and IHC assay showed overexpression of ATG5 and LC3 protein in the prefrontal cortex of Meth users. The cell death and neuronal degeneration were increased significantly based on Tunel assay and the stereological analysis in the Prefrontal cortex. Chronic METH exposure probably induces ATG5 and LC3 overexpression and neuronal cell death in the Prefrontal cortex of the postmortem cases.