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Background: Over the past two decades methamphetamine-related harms have increased in Australia. Previous analysis of methamphetamine-related deaths has covered limited timeframes, and largely focused on drug-toxicity deaths. This paper examines long-term trends in methamphetamine-related deaths over 20 years, including deaths due to a range of specific causes., Methods: Descriptive analyses were conducted on Australian methamphetamine-related deaths (2001-2023) by cause, extracted from the National Coronial Information System, an online database containing deaths reported to coroners in Australia and New Zealand. Joinpoint trend analyses were used to assess changes over time between 2001 and 2020 (with data from 2021 to 2023 likely incomplete and thus excluded)., Results: Unintentional drug toxicity was the cause of 49.8 % of methamphetamine-related deaths, intentional self-harm (including toxicity) 23.3 %, unintentional injury 15.1 %, natural causes 9.6 %, and assaults 2.3 %. Between 2001 and 2020, joinpoint analysis showed three trend change points among all-cause methamphetamine-related mortality rates, resulting in four distinct periods: two periods where they increased (2001-2006 - annual percentage change (APC) = 15.4 %; 2009-2016 - APC 25.5 %), and two where they decreased (2006-2009 - APC = -11.8 %; 2017-2020 - APC = -2.9 %). Similar patterns were evident among rates of intentional self-harm and unintentional injury. Deaths caused by unintentional drug toxicity saw two trend change points (2011, 2016), and rates increased across all three periods. Natural cause deaths had three trend change points (2007, 2010, 2015), and rates continued to rise after 2015, largely driven by increases in circulatory diseases., Conclusion: Cause-specific models highlighted diverse trends. Recent trends show unintentional drug toxicity deaths have slightly increased, intentional self-harm stabilised, and unintentional injury and assault deaths have declined. Deaths from natural causes involving methamphetamine continued to increase, highlighting a public health concern and a potential need for early circulatory disease screening among people who use methamphetamine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Importance: Mortality associated with methamphetamine use has increased markedly in the US. Understanding patterns of methamphetamine use may help inform related prevention and treatment., Objective: To assess the national trends in and correlates of past-year methamphetamine use, methamphetamine use disorder (MUD), injection, frequent use, and associated overdose mortality from 2015 to 2019., Design, Setting, and Participants: This cross-sectional study analyzed methamphetamine use, MUD, injection, and frequent use data from participants in the 2015 to 2019 National Surveys on Drug Use and Health (NSDUH). Mortality data were obtained from the 2015 to 2019 National Vital Statistics System Multiple Cause of Death files., Exposures: Methamphetamine use., Main Outcomes and Measures: Methamphetamine use, MUD, injection, frequent use, and overdose deaths., Results: Of 195 711 NSDUH respondents aged 18 to 64 years, 104 408 were women (weighted percentage, 50.9%), 35 686 were Hispanic individuals (weighted percentage, 18.0%), 25 389 were non-Hispanic Black (hereafter, Black) individuals (weighted percentage, 12.6%), and 114 248 were non-Hispanic White (hereafter, White) individuals (weighted percentage, 60.6%). From 2015 to 2019, overdose deaths involving psychostimulants other than cocaine (largely methamphetamine) increased 180% (from 5526 to 15 489; P for trend <.001); methamphetamine use increased 43% (from 1.4 million [95% CI, 1.2-1.6 million] to 2.0 million [95% CI, 1.7-2.3 million]; P for trend = .002); frequent methamphetamine use increased 66% (from 615 000 [95% CI, 512 000-717 000] to 1 021 000 [95% CI, 860 000-1 183 000]; P for trend = .002); methamphetamine and cocaine use increased 60% (from 402 000 [95% CI, 306 000-499 000] to 645 000 [95% CI, 477 000-813 000]; P for trend = .001); and MUD without injection increased 105% (from 397 000 [95% CI, 299 000-496 000] to 815 000 [95% CI, 598 000-1 033 000]; P for trend = .006). The prevalence of MUD or injection surpassed the prevalence of methamphetamine use without MUD or injection in each year from 2017 to 2019 (60% to 67% vs 37% to 40%; P for trend ≤.001). Adults with MUD or using injection were more likely to use methamphetamine frequently (52.68%-53.84% vs 32.59%; adjusted risk ratio, 1.62-1.65; 95% CI, 1.35-1.94). From 2015 to 2019, the adjusted prevalence of MUD without injection more than tripled among heterosexual women (from 0.24% to 0.74%; P < .001) and lesbian or bisexual women (from 0.21% to 0.71%; P < .001) and more than doubled among heterosexual men (from 0.29% to 0.79%; P < .001) and homosexual or bisexual men (from 0.29% to 0.80%; P = .007). It increased over 10-fold among Black individuals (from 0.06% to 0.64%; P < .001), nearly tripled among White individuals (from 0.28% to 0.78%; P < .001), and more than doubled among Hispanic individuals (from 0.39% to 0.82%; P < .001). Risk factors for methamphetamine use, MUD, injection, and frequent use included lower educational attainment, lower annual household income, lack of insurance, housing instability, criminal justice involvement, comorbidities (eg, HIV/AIDS, hepatitis B or C virus, depression), suicidal ideation, and polysubstance use., Conclusions and Relevance: This cross-sectional study found consistent upward trends in overdose mortality, greater risk patterns of methamphetamine use, and populations at higher risk for MUD diversifying rapidly, particularly those with socioeconomic risk factors and comorbidities. Evidence-based prevention and treatment interventions are needed to address surges in methamphetamine use and MUD.

Aims: To investigate liver-related and all-cause mortality among amphetamine users with hepatitis C virus (HCV) infection and compare this with opioid users with HCV infection and the uninfected general population., Methods: In this national register study of mortality in persons notified with HCV infection 1990-2015 and a substance-related diagnosis in Sweden, amphetamine users (n = 6,509) were compared with opioid users (n = 5,739) and a matched comparison group without HCV infection/substance use (n = 152,086)., Results: Amphetamine users were observed for 91,000 years and 30.1% deceased. Crude liver-related mortality was 1.8 times higher in amphetamine users than opioid users (crude mortality rate ratio 1.78, 95% CI 1.45-2.19), but there was no significant difference when adjusting for age and other defined risk factors. An alcohol-related diagnosis was associated with liver-related death and was more common among amphetamine users. Crude and adjusted liver-related mortality was 39.4 and 5.8 times higher, respectively, compared with the uninfected group. All-cause mortality was lower than in opioid users (adjusted mortality rate ratio 0.78, 95% CI 0.73-0.84), but high compared with the uninfected group. External causes of death dominated in younger ages whereas liver-related death was more common among older individuals., Conclusions: This national register study presents a higher crude risk of liver-related death among HCV-infected amphetamine users compared with opioid users or the uninfected general population. The higher risk of liver-related death compared with opioid users may be explained by lower competing death risk and higher alcohol consumption. Treatment of HCV infection and alcohol use disorders are needed to reduce the high liver-related mortality., Competing Interests: I have read the journal´s policy and the authors of this manuscript have the following competing interests: AH holds a position at Lund University which is sponsored by the Swedish state-owned gambling operator AB Svenska Spel. He also disposes research grants from the research councils of AB Svenska Spel, the state-owned alcohol monopoly Systembolaget, and from the research council of the Swedish Enforcement Agency and the Swedish Sports Federation. He is involved in a clinical research study receiving non-financial support from the commercial body Kontigo Care in the area of digital follow-up tools in the treatment of addictive disorders. He is also the national principal investigator of a prior pharmaco-epidemiological survey study conducted by the US research institute Research Triangle Institute and sponsored by the pharmaceutical company Shire, which supported the conduct of the study but did not provide personal fees to the individual researcher. The present competing interests are not involved in – and did not have any influence on – the present research project. OD has received research funding from Abbvie, MSD, and Gilead. MK has received honoraria for lectures/consultancy from AbbVie, Gilead, MSD, and has received research grants from Gilead. AD has given lectures with honoraria and/or been consultant for AbbVie, Gilead, and MSD. SA has received honoraria for lectures/consultancy from AbbVie, BMS, Gilead, MSD, and has received research grants from AbbVie and Gilead. CG, AJ, and HH declare no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The term 'amphetamine' refers to a class of synthetic drugs which includes methamphetamine. The latter is a globally popular drug of abuse which induces euphoria, affecting cognitive/psychomotor performance and sleep. It also provokes risk taking and violent behaviour. The central effects of methamphetamine are due to the overproduction of neurotransmitters, resulting in high levels of dopamine. In recent years, there have been significant increases in cases of methamphetamine abuse in North and South America, Australia and Asia due to its ready availability and low cost. The following review examines changing trends in methamphetamine use and problems that arise diagnostically in medico-legal cases in determining the significance of post-mortem blood levels, the relationship of these to ante-mortem levels, the possible effects on physical and psychological behaviours and the possible contribution of the drug to a lethal episode.

Methamphetamine use has emerged as a risk factor for intracerebral hemorrhage (ICH). We aim to investigate the clinical characteristics and outcomes of methamphetamine-associated ICH (Meth-ICH) versus Non-Meth-ICH. Patients with ICH between January 2011 and December 2017 were studied. Meth-ICH and Non-Meth-ICH were defined by history of abuse and urine drug screen (UDS). The clinical features of the 2 groups were explored. Among the 677 consecutive patients, 61 (9.0%) were identified as Meth-ICH and 350 as Non-Meth ICH. Meth-ICH was more common in Hispanics (14.6%) and Whites (10.1%) as compared to Asians (1.2%). Patients with Meth-ICH were more often younger (51.2 vs. 62.2 years, p < 0.001), male (77.0% vs. 61.4.0%, p < 0.05), and smokers (44.3% vs. 13.4%, p < 0.001). Non-Meth-ICH was more likely to have history of hypertension (72.61% v. 59%, p < 0.05) or antithrombotic use (10.9% vs. 1.6%, p < 0.05). There was no significant difference in clinical severity, hospital length of stay (LOS), rate of functional independence (29.5% vs. 25.7%, p = 0.534), or mortality (18.0% vs. 24.6%, p = 0.267) between the 2 groups. Methamphetamine use was not an independent predictor of poor outcome. Despite difference in demographics, Meth-ICH is similar to Non-Meth ICH in hospital course and outcome.

Anecdotal cases of reversible methamphetamine-associated cardiomyopathy (rMAC) have been reported, but not well understood. This study sought to determine the clinical characteristics, outcomes and predictors of reversibility among patients with rMAC as compared with patients with persistent MAC (pMAC). We retrospectively studied adult MAC patients with left ventricular ejection fraction (LVEF) ≤40% at a single center between 2004 and 2018. rMAC was defined as increase in LVEF by ≥20 points or to ≥50%. Those with persistent LVEF ≤40% constituted the pMAC group. 357 MAC cases were identified: 250 patients had pMAC and 107 had rMAC. After a median follow-up of 45 months (interquartile range 27 to 70), LVEF increased by 28.3 ± 6.9% in rMAC (p <0.001), whereas it was unchanged in pMAC (Δ: -0.5 ± 8.7%, p = 0.350). Heart failure hospitalizations and New York Heart Association Class III/IV heart failure were both significantly reduced for rMAC than the pMAC group. All-cause mortality was 21.6% overall, 28% in pMAC and 6.5% in the rMAC group (p <0.001). Kaplan-Meier survival curves demonstrated significantly higher cumulative survival for rMAC (Log Rank p <0.001). Multivariable logistic regression identified MA cessation (odds ratio/OR: 4.23, 95% confidence interval/CI: 2.47 to 7.38, p <0.001) and baseline right ventricular end systolic area (OR: 0.92, 95% CI: 0.87 to 0.97, p = 0.001) as strongly predictive of MAC reversal. In conclusion, MAC reversal is not uncommon and is associated with significant clinical improvement including reduced mortality. It can be facilitated by MA cessation when the cardiac chambers, especially the right ventricle, are not severely dilated., (Copyright © 2019 Elsevier Inc. All rights reserved.)

3,4-Methylenedioxymethamphetamine (MDMA), more commonly known as "ecstasy," is a semi-synthetic entactogenic phenylethylamine. In recent years it has gained popularity as a recreational drug whose use has registered an upward trend especially among adolescents and young adults. Despite its unwarranted reputation of being a "safe" drug, the actual scientific data denote that it actually leaves a trail of cardio-toxicity, above and beyond its neurotoxicity and other somatic effects. Both experimental and clinical data, in fact, indicate that ecstasy can alter cardiac function leading to rhythm disturbances, myocardial infarction, and even sudden cardiac death. We reviewed and summarized the bio-medical literature on the cardiovascular response to MDMA both in humans and laboratory animals. The aim was to elucidate the various pathophysiological mechanisms involved, as well as the clinical, autoptic, and experimental findings underlying MDMA-induced cardio-toxicity. Finally, an illustrative case report of ecstasy-induced adolescent death due to acute cardio-toxicity was described so as to highlight some key features.

Background and Aims: Amphetamines are the second most commonly used class of illicit drugs. We aimed to produce pooled estimates of mortality risks among people with regular or dependent use of amphetamines, with a focus upon all-cause mortality as well as specific causes of death., Design: Systematic review and meta-analysis of cohorts of people with problematic use or dependence on amphetamines with data on all-cause or cause-specific mortality., Setting and Participants: Of 4240 papers, 30 were eligible, reporting on 25 cohorts that measured all-cause mortality, drug poisoning, suicide, accidental injuries, homicide and cardiovascular mortality. Cohorts (n = 35-74 139) were in North America, several Nordic countries and Asia Pacific., Measurement: Titles/abstracts were independently screened by one reviewer and excluded those reviewed by a second reviewer. Full-text screening was by two reviewers with discrepancies resolved via a third reviewer. We extracted data on crude mortality rates (CMR) per 100 person-years (py), standardized mortality ratios (SMRs). We imputed SMRs where possible if not reported by study authors. We also calculated mortality relative risks. Data were pooled using random-effects models; potential reasons for heterogeneity were explored using subgroup analyses and meta-regressions., Findings: Twenty-three cohorts contributed data for the pooled all-cause CMR: 1.14 per 100 py [95% confidence interval (CI) = 0.92-1.42]. Pooled cause-specific mortality rates were: drug poisoning, 0.14 per 100 py (95% CI = 0.06-0.34); cardiovascular disease, 0.13 per 100 py (95% CI = 0.06-0.29); suicide, 0.20 per 100 py (95% CI = 0.07-0.55); accidental injury, 0.20 per 100 py (95% CI = 0.08-0.47) and homicide, 0.03 per 100 py (95% CI = 0.02-0.06). There was substantial heterogeneity for all pooled CMR estimates except homicide. The pooled all-cause SMR was 6.83 (95% CI = 5.27-8.84). Pooled cause-specific SMRS were: poisoning, 24.70 (95% CI = 16.67, 36.58); homicide, 11.90 (95% CI = 7.82-18.12); suicide, 12.20 (95% CI = 4.89-30.47); cardiovascular disease, 5.12 (95% CI = 3.74-7.00) and accidental injury, 5.12 (95% CI = 2.88-9.08)., Conclusions: People with regular or dependent amphetamine use are at elevated risk of a range of causes of mortality compared with people without regular or dependent amphetamine use., (© 2019 Society for the Study of Addiction.)

Background: To better characterize mortality among methamphetamine users, we estimated rates of all-cause mortality by HIV serostatus and smoking history in gay and bisexual men (GBM) treated for methamphetamine dependence, and explored associated clinical and socio-behavioral characteristics., Methods: We searched public records to identify deaths among men screened between 1998-2000 for a trial of outpatient therapy for GBM with methamphetamine dependence. Crude mortality rates (CMRs) were calculated, and standardized mortality ratios (SMRs) estimated, comparing data with historical information from CDC WONDER. Associations of mortality with HIV infection, tobacco use, and other factors were explored using Kaplan-Meier survival analysis and Cox proportional hazards models., Results: Of 191 methamphetamine-dependent GBM (median age 35 years; majority Caucasian), 62.8% had HIV infection, and 31.4% smoked tobacco at baseline. During the 20-year follow-up period, 12.6% died. Relative to controls, methamphetamine-dependent GBM had a three-fold higher 20-year SMR: 3.39, 95% CI: 2.69-4.09. Especially high mortality was observed among participants reporting tobacco use (adjusted HR 3.48, 95% CI: 1.54-7.89), club drug use prior to starting methamphetamine (2.63, 1.15-6.00), or other clinical diagnoses at baseline (3.89, 1.15-13.22). At 20 years, the CMR for HIV infected participants (7.7 per 1000 PY) was 1.5 times that for men without HIV (5.2 per 1000 PY; p = 0.22) and there was a 5-fold difference in CMRs for HIV infected tobacco smokers (16.9 per 1000 PY) compared to non-smokers (3.4 per 1000 PY; p < 0.01)., Conclusion: In our sample of methamphetamine-dependent GBM, concomitant HIV infection and tobacco use were associated with dramatic increases in mortality., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective and Background: Methamphetamine (Meth) is one of the most important central nervous system (CNS) stimulant abuse drugs that cause long-term or permanent damage to different regions of the brain, particularly hippocampus, by neuronal apoptosis and inflammation. In this study, we evaluated Nod-like Receptor Protein 3(NLRP3) and Nod-like Receptor Protein1 (NLRP1) Inflammasome Activation in the Hippocampal Region of postmortem Meth Chronic User., Methods: Molecular and histological analyses were conducted on the brain of 14 non-addicted and 11 Meth users separately. The expression level of NLRP1, NLRP3 was measured using western blotting and immunohistochemistry (IHC) techniques. Histopathological assessment was performed with stereological Cell Counting of hippocampal cells stained with hematoxylin and eosin (H et E). Moreover, Tunel staining was carried out in order to detect any kind of DNA damage., Results: Based on our findings using western blotting and immunohistochemistry assay, overexpression of NLRP1 and NLRP3 proteins in the hippocampal region of Meth addicts was observed. The stereological analysis in the hippocampus of the human brain revealed increased neurodegeneration. Furthermore, the increased rate of apoptosis and cell death were significant and confirmed by Tunel assay in the hippocampus of Meth groups., Conclusion: Chronic Meth abuse could result in increases of NLRP1 and NLRP3 and induction of inflammation and apoptosis in the hippocampus in Meth groups (Tab. 1, Fig. 9, Ref. 40).

Importance: Despite indications of increasing amphetamine availability and psychostimulant deaths in the United States, evidence across data sources is mixed, and data on amphetamine-related hospitalizations are lacking., Objective: To clarify trends in amphetamine-related hospitalizations and their clinical outcomes and costs in the United States., Design, Setting, and Participants: This repeated, cross-sectional study used hospital discharge data from the Healthcare Cost and Utilization Project National Inpatient Sample. The nationally representative sample included US adults (n = 1 292 300) who had amphetamine-related hospitalizations between January 1, 2003, and December 31, 2015. Multivariable logistic and Poisson regression models were used to examine in-hospital mortality and length of stay. Analysis of these data was conducted from November 2017 to August 2018., Exposure: Amphetamine dependence or abuse or amphetamine poisoning., Main Outcomes and Measures: Annual hospitalizations, in-hospital mortality, length of stay, transfer to another facility, and costs., Results: Over the 2003 to 2015 study period, there were 1 292 300 weighted amphetamine-related hospitalizations. Of this population, 541 199 (41.9%) were female and 749 392 (58.1%) were male, with a mean age of 37.5 years (95% CI, 37.4-37.7 years). Amphetamine-related hospitalizations, compared with other hospitalizations, were associated with age younger than 65 years (98.0% vs 58.0%; P < .001), male sex (60.3% [95% CI, 59.7%-60.8%] vs 41.1% [95% CI, 40.9%-41.3%]), Medicaid coverage (51.2% [95% CI, 49.8%-52.7%] vs 17.8% [95% CI, 17.5%-18.1%]), and residence in the western United States (58.5% [95% CI, 55.9%-61.0%] vs 18.9% [95% CI, 18.0%-19.8%]). Amphetamine-related hospitalizations declined between 2005 and 2008, and then increased from 55 447 hospitalizations (95% CI, 44 936-65 959) in 2008 to 206 180 hospitalizations (95% CI, 95% CI, 189 188-223 172) in 2015. Amphetamine-related hospitalizations increased to a greater degree than hospitalizations associated with other substances. Adjusted mean length of stay (5.9 [95% CI, 5.8-6.0] vs 4.7 [95% CI, 4.7-4.8] days; P < .001), transfer to another facility (26.0% [95% CI, 25.3%-26.8%] vs 18.5% [95% CI, 18.3%-18.6%]; P < .001), and mean in-hospital mortality (28.3 [95% CI, 26.2-30.4] vs 21.9 [95% CI, 21.6-22.1] deaths per 1000 hospitalizations; P < .001) were higher for amphetamine-related than other hospitalizations. Annual hospital costs related to amphetamines increased from $436 million (95% CI, $312 million-$559 million) in 2003 to $2.17 billion (95% CI, $1.95 billion-$2.39 billion) by 2015., Conclusions and Relevance: Given that amphetamine-related hospitalizations and costs substantially increased between 2003 and 2015, pharmacologic and nonpharmacologic therapies for amphetamine use disorders and a coordinated public health response are needed to curb these rising rates.

Characteristics of death attributed solely to methamphetamine toxicity (MT, n = 93) by forensic pathologists were examined and compared to cases of multiple drug toxicity (MDT, n = 634). The mean age of MT cases was 36.7 years, and 86.0% were male. Strenuous activity was reported in 12.9%. The most common witness observations were: collapse (60.3%), difficulty in breathing (36.2%), and hyperthermia (27.6%). MT cases had higher blood methamphetamine (0.54 vs. 0.11 mg/L) and amphetamine (0.04 vs. 0.02 mg/L) concentrations and lower likelihoods for opioids (12.5% vs. 80.9%), hypnosedatives (27.3 vs. 60.7%), antidepressants (14.8 vs. 29.8%), and antipsychotics (9.1 vs. 19.7%). MT cases had significantly heavier hearts than MDT cases (423.4 vs. 385.8 g) and were more likely to have cardiomegaly (37.1 vs. 20.4%) and replacement fibrosis (25.7 vs. 14.5%). The clinical picture was of a sudden cardiac event in a middle-aged man with a high methamphetamine concentration. Cardiovascular signs of heavy methamphetamine use are frequently seen., (© 2017 American Academy of Forensic Sciences.)

Background: Opioids and stimulants (e.g., cocaine or methamphetamine/amphetamine [MAMP]) are major contributors to acute substance toxicity deaths. Causes of stimulant death have received little attention. We sought to characterize and compare causes of death and significant contributing conditions among persons who died from acute opioid, cocaine, or MAMP toxicity., Methods: We identified all opioid, cocaine, or MAMP deaths in San Francisco from 2005 to 2015 through the California Electronic Death Reporting System. Multivariable logistic regression analyses were used to estimate associations between acute substance toxicity deaths (opioid versus stimulant; cocaine versus MAMP), additional reported causes of death, and significant contributing conditions most often linked to opioid and stimulant use., Results: From 2005-2015, there were 1252 opioid deaths and 749 stimulant deaths. Cocaine accounted for most stimulant deaths. Decedents with cardiac or cerebral hemorrhage deaths had higher adjusted odds of death due to acute stimulant toxicity versus acute opioid toxicity (aOR = 4.79, 95%CI = 2.88-7.96, p < 0.01; aOR = 58.58, 95%CI = 21.06-162.91, p < 0.01, respectively); no statistically significant associations were found for cocaine compared to MAMP deaths. Significant contributing cardiac conditions were associated with higher adjusted odds of stimulant compared to opioid (aOR = 1.46, 95%CI = 1.19-1.79, p < 0.01) and cocaine compared to MAMP death (aOR = 1.66, 95%CI = 1.13-2.45, p = .01)., Conclusions: Stimulant compared to opioid deaths tended to involve cardiac or cerebrovascular causes of death, and cocaine deaths were more likely than MAMP deaths to involve significant contributing cardiac conditions. Mounting evidence suggests that stimulant use be considered a cardio/cerebrovascular risk factor and clinical care be adjusted to address this heightened risk., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: To (1) assess trends in the number and mortality rates of methamphetamine-related death in Australia, 2009-15; (2) assess the characteristics and the cause, manner and circumstances of death; and (3) assess the blood methamphetamine concentrations and the presence of other drugs in methamphetamine-related death., Design: Analysis of cases of methamphetamine-related death retrieved from the National Coronial Information System (NCIS)., Setting: Australia., Cases: All cases in which methamphetamine was coded in the NCIS database as a mechanism contributing to death (n = 1649)., Measurements: Information was collected on cause and manner of death, demographics, location, circumstances of death and toxicology., Findings: The mean age of cases was 36.9 years, and 78.4% were male. The crude mortality rate was 1.03 per 100 000. The rate increased significantly over time (P < 0.001), and at 2015 the mortality rate was 1.8 [confidence interval (CI) = 1.2-2.4] times that of 2009. Deaths were due to accidental drug toxicity (43.2%), natural disease (22.3%), suicide (18.2%), other accident (14.9%) and homicide (1.5%). In 40.8% of cases, death occurred outside the major capital cities. The median blood methamphetamine concentration was 0.17 mg/l, and cases in which only methamphetamine was detected had higher concentrations than other cases (0.30 versus 0.15 mg/l, P < 0.001). The median blood methamphetamine concentration varied within a narrow range (0.15-0.20 mg/l) across manner of death. In the majority (82.8%) of cases, substances other than methamphetamine were detected, most frequently opioids (43.1%) and hypnosedatives (38.0%)., Conclusions: Methamphetamine death rates doubled in Australia from 2009 to 2015. While toxicity was the most frequent cause, natural disease, suicide and accident comprised more than half of deaths., (© 2017 Society for the Study of Addiction.)

Background: Amphetamine-associated cardiomyopathy (AAC) is becoming an increasingly recognised entity. The characteristics and outcomes of these patients are poorly understood., Methods: Thirty patients admitted with heart failure and echocardiographic evidence of cardiomyopathy between 2005 and 2014 and who had a documented history of amphetamine abuse that was considered an important factor in the causation of their cardiomyopathy were retrospectively identified., Results: Mean age at presentation was 40±10 years with a male predominance (n=25, 83%). The majority were of indigenous Maori ethnicity. At presentation, four patients were in cardiogenic shock. Five patients required intensive care unit (ICU) admission for inotropic support and mechanical ventilation. Fifteen had severe left ventricular (LV) dilation (mean LV end-diastolic dimension 6.8±1.0cm) and all patients had severe LV dysfunction (mean LV ejection fraction 22±8%). Despite optimal heart failure therapy, LV size remained significantly dilated with minimal improvement in LV function. During median follow-up of 18 months, five patients died from end-stage heart failure and 17 had at least one readmission with decompensated heart failure., Conclusion: Amphetamine-associated cardiomyopathy was seen predominantly in young indigenous Maori men. They presented with severe cardiomyopathy, often requiring ICU admission. Severe LV dilation and significant LV dysfunction persisted despite treatment and mortality was high., (Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Context: Lisdexamfetamine is a pro-drug stimulant that requires the enzymatic hydrolysis of lysine from dexamphetamine for pharmacologic effects. There is limited information comparing non-therapeutic lisdexamfetamine and dextroamphetamine exposures., Objective: The objective was to compare lisdexamfetamine exposures with dextroamphetamine/amphetamine extended release and dextroamphetamine/amphetamine immediate release., Methods: A retrospective observational case series of single-substance exposures to lisdexamfetamine, dextroamphetamine/amphetamine extended release, or dextroamphetamine/amphetamine immediate release reported to the National Poison Data System from 2007 to 2012 was performed. Data were analyzed for demographics, reason, clinical effects, management site, and outcomes., Results: There were 23,553 exposures: lisdexamfetamine (7,113), dextroamphetamine/amphetamine extended release (6,245), and dextroamphetamine/amphetamine immediate release (10,195). The most frequent clinical effects observed for lisdexamfetamine, dextroamphetamine/amphetamine extended release, and dextroamphetamine/amphetamine immediate release were agitation (19.8%, 21.7%, and 25.1%, respectively) and tachycardia (19.2%, 22.8%, and 23.9%, respectively). The reason was most often exploratory (93.4%) in children < 6 years and therapeutic error (65.6%) in children aged 6-12 years. In adolescents and adults most common reasons were suicide attempts (28.4%) followed by abuse (19.5%) and therapeutic errors (18.8%). Overall, 61.6% of cases were managed in a health care facility, with the majority treated in the emergency department only. The majority of cases (76.0%) experienced no or minor effects. More serious outcomes (moderate/major/death) occurred in 21.2% of lisdexamfetamine, 24.7% of dextroamphetamine/amphetamine extended release, and 25.5% of dextroamphetamine/amphetamine immediate release. There were 4 deaths (1 dextroamphetamine/amphetamine extended release and 3 dextroamphetamine/amphetamine immediate release). In patients aged 6 years and more, abuse/misuse was more frequently reported for dextroamphetamine/amphetamine immediate release (32.5%) and dextroamphetamine/amphetamine extended release (23.0%) than that for lisdexamfetamine (13.5%). The odds of abuse/misuse was 2.3 (95% confidence interval [CI]: 2.0-2.4) times higher for dextroamphetamine/amphetamine immediate release than that for lisdexamfetamine and dextroamphetamine/amphetamine extended release combined; the odds of dextroamphetamine/amphetamine extended release abuse/misuse was 1.9 (95% CI: 1.7-2.2) times higher than lisdexamfetamine. In 2011, the number of lisdexamfetamine abuse/misuse cases exceeded dextroamphetamine/amphetamine extended release by approximately 26% and plateaued in 2012, but was significantly lower (∼75%) than dextroamphetamine/amphetamine immediate release., Conclusions: Toxic effects were similar for all three drugs. Although the majority of cases were treated at health care facilities, the majority of patients experienced no effects or minor toxicity. Serious outcomes occurred in approximately 21% of lisdexamfetamine and 25% of dextroamphetamine/amphetamine extended release and dextroamphetamine/amphetamine immediate release. Lisdexamfetamine may have less abuse potential, especially compared with the immediate-release dextroamphetamine/amphetamine formulation.

This study examines causes of death, years of life lost, and health and drug use characteristics associated with mortality over an 8 to 10 year period in a sample of methamphetamine users who had and had not received substance use disorder treatment (N = 563). Decedents reported initiating their methamphetamine use for different reasons than surviving methamphetamine users, and some of these differences varied by treatment status. Study findings provide additional detail on long-term health and mortality outcomes in a diverse sample of methamphetamine users, which may inform public health strategies targeting the comparable and divergent needs of treated and untreated populations.

This study examined mortality and predictors of death in 1,396 primary amphetamine users (85% males) who were interviewed with the Addiction Severity Index in the Swedish criminal justice system during 2000-2006 and followed through 2008. Forty-nine clients deceased (standardized mortality ratio 4.1 [3.0-5.4]), at least 84% of deaths were violent or drug-related (12% suicides), and Cox regression analysis indicated that death was associated with frequent use of sedatives and less frequent use of amphetamine. No female deaths were observed; death and male gender were associated in binary analysis. Implications for diagnostics and treatment are discussed.

For nearly 30 years, there has been a steady flow of research papers highlighting the dangers of MDMA and the implications for ecstasy users. After such a long time, it would be reasonable to expect that these dangers would be obvious due to the large number of ecstasy users. The available evidence does not indicate that there are millions of ecstasy users experiencing any problems linked to their ecstasy use. The "precautionary principle" suggests that, in the absence of knowing for certain, "experts" should argue that MDMA be avoided. However, this may have been taken too far, as the dire warnings do not seem to be reducing with the lack of epidemiological evidence of clinically relevant problems. The "ecstasy paradigm" is one way of articulating this situation, in that the needs of research funders and publication bias lead to a specific set of subcultural norms around what information is acceptable in the public domain. By digging a little deeper, it is easy to find problems with the evidence base that informs the public debate around MDMA. The key question is whether it is acceptable to maintain this status quo given the therapeutic potential of MDMA.

Background: Understanding the mortality rate of methamphetamine users, especially in relation to other drug users, is a core component of any evaluation of methamphetamine-related harms. Although methamphetamine abuse has had a major impact on United States (U.S.) drug policy and substance-abuse treatment utilization, large-scale cohort studies assessing methamphetamine-related mortality are lacking., Methods: The current study identified cohorts of individuals hospitalized in California from 1990 to 2005 with ICD-9 diagnoses of methamphetamine- (n=74,139), alcohol- (n=582,771), opioid- (n=67,104), cannabis- (n=46,548), or cocaine-related disorders (n=48,927), and these groups were followed for up to 16 years. Age-, sex-, and race-adjusted standardized mortality rates (SMRs) were generated., Results: The methamphetamine cohort had a higher SMR (4.67, 95% CI 4.53, 4.82) than did users of cocaine (2.96, 95% CI 2.87, 3.05), alcohol (3.83, 95% CI 3.81, 3.85), and cannabis (3.85, 95% CI 3.67, 4.03), but lower than opioid users (5.71, 95% CI 5.60, 5.81)., Conclusions: Our study demonstrates that individuals with methamphetamine-use disorders have a higher mortality risk than those with diagnoses related to cannabis, cocaine, or alcohol, but lower mortality risk than persons with opioid-related disorders. Given the lack of long-term cohort studies of mortality risk among individuals with methamphetamine-related disorders, as well as among those with cocaine- or cannabis-related conditions, the current study provides important information for the assessment of the comparative drug-related burden associated with methamphetamine use., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: For adults in general population community settings, data regarding long-term course and outcomes of illicit drug use are sparse, limiting the formulation of evidence-based recommendations for drug use screening of adults in primary care., Objective: To describe trajectories of three illicit drugs (cocaine, opioids, amphetamines) among adults in community settings, and to assess their relation to all-cause mortality., Design: Longitudinal cohort, 1987/88-2005/06., Setting: Community-based recruitment from four cities (Birmingham, Chicago, Oakland, Minneapolis)., Participants: Healthy adults, balanced for race (black and white) and gender were assessed for drug use from 1987/88-2005/06, and for mortality through 12/31/2008 (n = 4301), Measurements: Use of cocaine, amphetamines, and opioids (last 30 days) was queried in the following years: 1987/88, 1990/91, 1992/93, 1995/96, 2000/01, 2005/06. Survey-based assessment of demographics and psychosocial characteristics. Mortality over 18 years., Results: Trajectory analysis identified four groups: Nonusers (n = 3691, 85.8%), Early Occasional Users (n = 340, 7.9%), Persistent Occasional Users (n = 160, 3.7%), and Early Frequent/Later Occasional Users (n = 110, 2.6%). Trajectories conformed to expected patterns regarding demographics, other substance use, family background and education. Adjusting for demographics, baseline health status, health behaviors (alcohol, tobacco), and psychosocial characteristics, Early Frequent/Later Occasional Users had greater all-cause mortality (Hazard Ratio, HR = 4.94, 95% CI = 1.58-15.51, p = 0.006)., Limitations: Study is restricted to three common drugs, and trajectory analyses represent statistical approximations rather than identifiable "types". Causal inferences are tentative., Conclusions: Four trajectories describe illicit drug use from young adulthood to middle age. Two trajectories, representing over one third of adult users, continued use into middle age. These persons were more likely to continue harmful risk behaviors such as smoking, and more likely to die.

Paramethoxymethamphetamine (PMMA) is an emerging and prevalent psychoactive drug with a structure analogous to amphetamine and related psychostimulants. However, the neurobehavioral effect is only studied in experimental animals and is barely mentioned in human. The authors report the antemortem neurobehavioral manifestations in 8 patients with PMMA use. There were 2 different antemortem presentations. The first group of patients showed delirium, hypertalkativity, and incoherence speech and then turned into convulsion and death. They did not exhibit the typical hyperdopaminergic movement disorder. The second group of patients gradually fell asleep and then suffered respiratory or cardiovascular collapse. The heart blood PMMA level was higher in the second group than in the first group of patients. Forensic autopsy showed variable findings, ranging from no remarkable change to significant pathological damage similar to serotonin syndrome in both groups of patients. PMMA seems to enhance serotoninergism than dopaminergism, and exerts a concentration-related dual effect on human.

Introduction and Aims: Methamphetamine use leads to increased likelihood of premature death. The authors investigated the causes of death and risk of mortality in a large cohort of patients with methamphetamine dependence., Design and Methods: A cohort of 1254 subjects with methamphetamine dependence, admitted to a psychiatric centre in Taiwan from January 1990 to December 2007, was retrospectively studied. Diagnostic and sociodemographic data for each subject were extracted from the medical records based on a chart review process. Mortality data were obtained by linking to the National Death Certification System and standardised mortality ratios (SMRs) were estimated. The risk and protective factors for all-cause deaths were explored by means of survival analyses., Results: During the study period, 130 patients died. Of them, 63.1% died unnatural deaths, while the remaining 36.9% died natural deaths. The 1 year cumulative rates for unnatural and natural deaths were 0.018 and 0.006, respectively, and the 5 year rates were 0.046 and 0.023, respectively. The cohort had excessive mortality (SMR = 6.02), and women had a higher SMR for unnatural deaths than men (26.19 vs. 9.82, P = 0.001). For all-cause deaths, comorbidity with other substance use disorders was associated with increased risk of death, despite that being married was associated with a reduced risk., Discussion and Conclusions: A substantial proportion of the deceased died natural deaths, but most died unnatural deaths. The findings show significant evidence to provide valuable insight into premature deaths among methamphetamine-dependent users. This information is valuable for development of prevention and intervention programs., (© 2010 Australasian Professional Society on Alcohol and other Drugs.)

Background/aims: Despite being amphetamine derivatives, MDMA and its analogues show a number of clinical pharmacological differences with respect to both amphetamine (AMP) and methylamphetamine (METH). We aimed here at reporting and analysing information relating to the socio-demographics and clinical circumstances of the AMP-type stimulant-related deaths for the whole of the UK., Methods: Data (1997-2007) were taken from the National Programme on Substance Abuse Deaths (np-SAD) database, collecting information from UK coroners/procurators fiscal. To calculate rates of fatalities per 100,000 users, appropriate AMP/METH and ecstasy users' numbers were taken from the 2001-2007 British Crime Survey., Results: Overall, 832 AMP/METH- and 605 ecstasy (mostly MDMA and methylenedioxyamphetamine/MDA)-related deaths were respectively identified. In comparison with AMP/METH victims, the ecstasy ones were more likely to be younger (28.3 vs. 32.7 years; p < 0.0001) and less likely to be known as drug users (PR = 1.9; CI 1.5-2.6). Ecstasy was more likely to be identified on its own than AMP/METH (p = 0.0192). Contributory factors were more frequently mentioned by coroners in the 'AMP/METH-only' (106 cases) group than in the 'ecstasy-only' (104 cases) one (p = 0.0043). Both poly- and monodrug AMP/METH fatalities per 100,000 16- to 59-year-old users were significantly more represented than ecstasy fatalities (respectively 17.87 +/- 4.77 deaths vs. 10.89 +/- 1.27; p = 0.000; 2.09 +/- 0.88 vs. 1.75 +/- 0.56; p = 0.0096). However, mono-intoxication ecstasy fatalities per 100,000 16- to 24-year-old users were significantly more represented than AMP/METH fatalities (1.67 +/- 0.52 vs. 0.8 +/- 0.65; p = 0.0007)., Conclusion: With respect to AMP/METH, ecstasy was here more typically identified in victims who were young, healthy, and less likely to be known as drug users. AMP/METH high mortality rates may be explained by users' high levels of physical co-morbidity; excess ecstasy-related fatality rates in young users may be a reason for concern. Although the coroners' response rate was of 90-95%, study limitations include both reporting inconsistency over time and lack of routine information on drug intake levels prior to death., ((c) 2010 S. Karger AG, Basel.)

Aims: To report the results of a comprehensive literature search of studies of mortality among people who use amphetamines., Design and Setting: Three electronic databases were searched (EMBASE, Medline and PsycINFO) and "grey" literature was located. Shortlists of papers were circulated to experts to ascertain whether any important papers had been missed. Papers were hand-searched to retrieve any additional relevant articles., Measurements: Studies meeting inclusion criteria were prospective cohort studies examining mortality risk among dependent and problematic amphetamine users. Crude mortality rates (CMR/100PY) and standardised mortality ratios (SMRs) were the primary outcome measures considered. Data on overall mortality, and rates for specific causes of death, were of interest., Findings: 2187 articles and 9 grey literature sources were obtained. After thorough review, 72 articles were identified as reporting on amphetamine-related mortality, 7 provided data from cohort studies of users. An additional study of Swedish military conscripts was identified by the authors during correspondence with other researchers. The geographic spread of cohorts was restricted to high income countries with the exception of one Thai study; reporting of standard parameters in mortality studies was often sparse. The estimated CMRs ranged from 0 in Australia to 2.95 (1.46-4.59) in Thailand. The Czech cohort reported the only SMR: 6.22 overall, males: 5.87, females: 7.84., Conclusions: Given the widespread use of amphetamines, the known non-fatal adverse effects of use and the mortality rates reported here, cohort studies investigating the morbidity and mortality associated with such drug use should be a research priority.

Aim: To examine the demographic characteristics, circumstances, toxicology and major organ pathology of MDMA-related deaths in Australia., Methods: Retrospective review of cases in which MDMA was a cause of death, as identified from the National Coronial Information System., Results: 82 cases over a 5-year period were identified. The majority of decedents were male (83%), with a median age of 26 years. Deaths were predominantly due to drug toxicity (82%), with MDMA the sole drug causing death in 23% of cases, and combined drug toxicity in 59% of cases. The remaining deaths (18%) were primarily due to pathological events/disease or injury, with MDMA a significant contributing condition. Cardiovascular pathology, typically atherosclerosis, was detected in 58% of decedents, with moderate-severe atherosclerosis in 23% of cases. The prevalence of such pathology is higher than that expected among similarly aged members of the general population. Cerebrovascular pathology, primarily cerebral haemorrhage and hypoxic damage, was present in 12% of cases., Conclusions: MDMA has contributed to a clinically significant number of deaths in Australia. The prevalence of cardiovascular pathology was similar to that among methamphetamine and cocaine fatalities. Whilst cardiovascular pathology may reflect the use of other stimulants, the cardiotoxic properties of MDMA have been well-documented. Future studies examining MDMA-related morbidity and mortality in the context of other risk factors are recommended. Overall, the current study highlights the need to educate users about the potential harms of MDMA use, particularly that in conjunction with other stimulants, opioids and alcohol, which are known to increase overall toxicity.

In the present study, the effects of amphetamine-class drugs were examined in cases reported to the Victorian coroner from 2001 to 2005 to determine if death can occur from the use of amphetamine-class drugs alone. A total of 169 cases were reviewed where a forensic autopsy detected amphetamine(s) in the blood. Pathology, toxicology, and police reports were analyzed in all cases to ascertain the involvement of amphetamine-class drugs in these deaths. In Victoria, methamphetamine (MA) is the principal abused amphetamine-class followed by methylenedioxymethamphetamine (MDMA). There were six cases in which a cerebral hemorrhage caused death and three cases in which serotonin syndrome was established as being caused by the interaction of MDMA and moclobemide. There were 19 cases in which long-term use of amphetamines was associated with heart disease. There were three cases where amphetamine-class drugs alone were regarded as the cause of death, of which two cases exhibited high levels of MDMA and lesser amounts of MA and/or amphetamine. There were no cases in which significant natural disease was absent and death was regarded as caused by the use of MA. There was no correlation between blood concentration of drug and outcome.

Introduction: This investigation utilized spatial scan statistics, geographic information systems, and multiple data sources to assess spatial clustering of statewide methamphetamine-related incidents. Temporal and spatial associations with regulatory interventions to reduce access to precursor chemicals (pseudoephedrine) were also explored., Methods: Four statewide data sources were utilized including regional poison control center statistics, fatality incidents, methamphetamine laboratory seizures, and hazardous substance releases involving methamphetamine laboratories. Spatial clustering of methamphetamine incidents was assessed using SaTScan. SaTScan was also utilized to assess space-time clustering of methamphetamine laboratory incidents, in relation to the enactment of regulations to reduce access to pseudoephedrine., Results: Five counties with a significantly higher relative risk of methamphetamine-related incidents were identified. The county identified as the most likely cluster had a significantly elevated relative risk of methamphetamine laboratories (RR = 11.5), hazardous substance releases (RR = 8.3), and fatalities relating to methamphetamine (RR = 1.4). A significant increase in relative risk of methamphetamine laboratory incidents was apparent in this same geographic area (RR = 20.7) during the time period when regulations were enacted in 2004 and 2005, restricting access to pseudoephedrine. Subsequent to the enactment of these regulations, a significantly lower rate of incidents (RR = 0.111, p = 0.0001) was observed over a large geographic area of the state, including regions that previously had significantly higher rates., Conclusions: Spatial and temporal scan statistics can be effectively applied to multiple data sources to assess regional variation in methamphetamine-related incidents, and explore the impact of preventive regulatory interventions.

Background: The association of methamphetamine exposure and outcomes after trauma is not known., Methods: This study included trauma patients who underwent alcohol and illicit drug screening. Patients who had a screen positive for Methamphetamine only [METH (+)] were compared with patients with a completely negative screen for illicit drugs or alcohol [TOX (-)]. Patients with polysubstance or alcohol abuse were excluded. Logistic regression was used to determine whether METH (+) status was independently associated with injury patterns or outcomes. Associations were further evaluated by patient matching with respect to age, gender, mechanism, injured body area abbreviated injury scores, and injury severity., Results: There were 5,372 patients eligible where 526 (9.8%) were METH (+). On multivariate analysis, the METH (+) group had a significantly higher adjusted rate of intensive care unit (ICU) admission but there was no difference in mortality or complications or ICU stay. On matching, there was no difference in mortality (11.1% vs. 10.9%, p = 0.87), complication rate (5.6% vs. 4.2%, p = 0.40), and lengths of ICU and hospital stay but the METH (+) group had a higher rate of laparotomy., Conclusion: Patients exposed to Methamphetamines do not have increased mortality or complications or lengths of ICU and hospital stay. However, they are more likely to require admission to the ICU.

Objective: Methamphetamine is a stimulant widely abused in the United States. The objective of this study was to demonstrate an association of methamphetamine use and ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage and to further reveal the underlying vascular pathology using neuroimaging and pathology., Methods: This was a retrospective study based on medical chart review of admissions to the neurovascular service of a tertiary care medical center from January 2003 to July 2007. Cases included patients who used methamphetamine as documented by history or urine toxicology screening., Results: From 1,574 records, 30 cases were identified. The mean age of patients was 43 years and the discharge diagnoses included ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. All subarachnoid hemorrhages were aneurysmal with the majority of the aneurysms located in the anterior circulation. The majority of strokes were located in the anterior circulation. In many cases, radiologic imaging confirmed arterial stenoses in the vascular distribution of the stroke. One patient who presented with ischemic stroke had severe atherosclerosis of bilateral common, internal, and external carotid arteries. On pathology, there was no evidence of inflammation or necrosis to suggest vasculitis as a possible etiology., Conclusions: Methamphetamine use is associated with ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage, especially among young patients. We showed no evidence that the ischemic stroke associated with methamphetamine use is due to an inflammatory etiology but may be due to a process of accelerated atherosclerosis.

Aim: To examine the demographic characteristics, circumstances of death, toxicological results and major organ pathology of methamphetamine-related deaths in Australia., Design: Retrospective review of coronial files., Setting: Australia., Methods: Cases in which methamphetamine was listed as a cause of death were identified from the National Coronial Information System (NCIS)., Findings: A total of 371 cases were identified. The mean age of decedents was 32.7 years; 77% were male and 35% were employed. Route of administration was predominantly by injection (89%). Drugs other than methamphetamine were detected in 89% of cases, most commonly benzodiazepines (41%) and morphine (36%). The median blood methamphetamine concentration was 0.2 mg/l (range 0.02-15.0 mg/l). Deaths were overwhelmingly accidental, with 14% determined to be suicides, and occurred in a private home (71%). Cardiovascular pathology, typically coronary artery atherosclerosis, was detected in 54% of decedents. Cerebrovascular pathology, most commonly cerebral haemorrhage and hypoxia, was present in 20% of cases., Conclusions: Methamphetamine has contributed to a substantial number of deaths in Australia. Users need to be informed of the potential harms of methamphetamine use, particularly those associated with the cardiotoxicity of methamphetamine and the use of methamphetamine in conjunction with other drugs.

Deaths from 1992 through 2003 related to sauna bathing in Sweden were collected from a national computer data base comprising all medicolegal autopsies, generating 77 cases included in this study. Of all deaths, 82% were men, most of them middle-aged. The geographic distribution seemed to be roughly related to the population density. Most bathers died on a weekend, and 84% were found dead in a sauna. In 69 cases, the blood alcohol concentration was determined; 49 (71%) of these tested positive, often with high concentrations. In 65 cases, a major disease/state that could explain death was identified; 34 (44%) of these deaths were related to alcohol and 18 (23%) cardiovascular. Other causes of death were drowning, CO poisoning, O2 deprivation, amphetamine intoxication, and burn injuries. In 13 cases, the cause of death remained undetermined. The results indicate that sauna habits in Sweden are similar to those in Finland but probably less common. The most important risk group is middle-aged men, especially those with heavy alcohol consumption. Among the cases found dead in a sauna, all but 2 were found alone. Obviously, bathing alone is a risk factor that can easily be avoided and should perhaps be emphasized more.

Objective: To identify causes of death among Norwegian drug abusers and to investigate the risk factors for fatal overdose and other causes of death, with specific attention to ageing and duration of abuse., Methods: In a cohort of 501 drug abusers admitted to treatment in the period 1981-1991, mortality has been calculated as incidence rates. The analyses of time to death were conducted as proportional hazard regression models using a competing risk approach., Results: Crude incidence rates for all deaths and overdose deaths did not vary with age. For non-overdose deaths, however, the incidence was significantly higher after the age of 40. Explanatory factors associated with age at fatal overdoses are also associated with age at death by other causes. At every age the risk of death was higher with a long-term abuse of drugs, and more so for fatal overdose than for death by other causes., Conclusions: With respect to fatal overdose duration of abuse, but not ageing, is found to be a risk factor. With respect to death by other causes both ageing and duration of abuse are factors associated with such death.

California Substance Abuse Research Consortium (SARC) meetings have become a mainstay in supporting the exchange of new alcohol and other drug information on research to policy and other initiatives throughout the state. A cornerstone of SARC is a discussion of regional substance abuse patterns and trends. This article provides readers with a brief overview of recently released methamphetamine statistics, as well as a more detailed review of the methamphetamine information presented during the substance abuse epidemiology portion of the September 2005 meeting, as presented for Kern County, Los Angeles County, San Diego County, the San Francisco Bay Area, and the state of California.

In the last decade, a global trend of escalating ecstasy (MDMA, MDA, MDEA, MBDB) use was observed. Mentions on medical death certificates, last year's ecstasy use, number of drug offenders, seizures, prices and dosage levels figures were used for this descriptive and correlational study. Figures (1994-2003) were taken from the UK General Mortality Registers, from the Home Office Statistical Bulletins, from the British Crime Survey and from those reported to both the National Crime Intelligence and Forensic Science Services. A total of 394 ecstasy deaths mentions were here identified from the UK; in 42% of cases ecstasy was the sole drug mentioned. Overall, number of fatalities showed a year-per-year increase and positively correlated with: prevalence of last year's use (p < 0.01); number of offenders (p < 0.01) and number of seizures (p < 0.01) but negatively correlated with ecstasy price (p < 0.05). Price negatively correlated with: prevalence of last year's use (p < 0.001) and number of seizures (p < 0.01); but positively correlated with average MDMA dosage per tablet (p < 0.01). MDA, MDEA and MBDB accounted for a significant proportion of tablets only up to 1997, but not afterwards. Increasing production with a concomitant decrease in ecstasy price may have facilitated an increase in consumption levels and this, in turn, may have determined an increase in number of ecstasy deaths mentions. Only medical death certificates and not coroners' reports at the end of their inquests were here analysed; no data were available in respect of other drugs use and toxicology results.

Previous research has shown that most transitions into abstinence happens in the stages of the drug career quickly after the first treatment episode. Mortality is somewhat reduced for patients who become abstinent, but remains high for patients who remain addicted. However, even among substance abusers who become abstinent, mortality is often higher than in the general population. A consecutive sample of drug users admitted for detoxification was followed for 15 years. Face-to-face interviews were conducted at 5-year follow-up. At 15-year follow-up, 24% were dead. Cox proportional hazard regression was conducted to predict mortality for continuous variables, and Gehan's Wilcoxon test was used to predict mortality for dichotomous variables. Psychiatric status at 5-year follow-up was predictive of 15-year mortality, whereas abstinence was not. Subjects who later died had higher scores on the Symptom Checklist 90 [SCL-90] Global Severity Index, lower meaningfulness on the Sense of Coherence scale, and lower Global Assessment of Functioning [GAF] scores at 5-year follow-up. By contrast, there were no associations between baseline drug use and antisocial personality disorder diagnoses and mortality. Psychiatric treatment, including psychotherapy, may be more life-saving for substance abusers than drug-abuse services.

Abuse of amphetamine (AMP) and its derivatives, such as 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), 3,4-methylenedioxyethylamphetamine (MDEA, MDE), and 3,4-methylenedioxyamphetamine (MDA) is an important public issue. Fatalities following ingestion of these substances are not infrequent in current forensic practice. The aim of this study was twofold. Firstly, considering the wide range of blood levels reported in fatalities, to provide insight into the interpretation of a quantified blood level and, secondly, to examine and discuss possible causes, mechanisms and manners of death. All the medico-legal files between January 1976 and December 2004 were skimmed through to investigate whether amphetamine and/or derivatives were involved in the fatal outcome. Particularly, in addition to overdose cases due to or including amphetamines, all amphetamines-related fatalities were examined. In addition to AMP, MDMA, MDEA, and MDA, two other amphetamine derivatives, namely 4-methylthioamphetamine (4-MTA) and para-methoxyamphetamine (PMA) were considered. In 34 fatalities, amphetamines were involved and the majority were men, under the age of 25 years. A wide range of blood levels was found: e.g. MDMA blood concentrations in cases of 'pure' intoxication were found between 0.27 and 13.51 microg/ml. The age and sex distribution as well as the broad range of quantified amphetamines blood levels were in line with those reported in the literature. In our study group, 'pure' intoxications with amphetamines, polydrug overdoses, and the combination of amphetamines use and polytrauma were the most prominent causes of death. Considering the manner of death in these fatalities, unintentional overdoses were most frequent, though suicides, traffic accidents, and criminal offences associated with amphetamines use also accounted for significant percentages. Acute to subacute cardiopulmonary failure was the most frequent mechanism of death, followed by (poly)trauma, mechanical asphyxia, and hyperthermia, respectively. In conclusion, although amphetamines-related fatalities are only a fraction of the total number of fatalities studied at our Department, their contribution to current forensic practice has been increasing during the last few years. As there is still considerable debate as to what level of amphetamines can be toxic or even potentially lethal, it is strongly advisable to interpret the anatomo-pathological findings and the toxicological results together in arriving at a conclusion. This guideline is important in view of the different possible mechanisms of death which implicate quite different survival times following intake of amphetamine and/or its derivatives (e.g. cardiopulmonary complications, hyperthermia).

Cerebral hemorrhages are rare complications that occur after the consumption of amphetamine; the mortality rate is estimated at 50 %. It is assumed that cerebral hemorrhages are caused by amphetamine-induced hypertensive crises coinciding with pre-existing vascular alterations (congenital vascular malformations, vasculitis). In the present case report, a 40-year-old man, who is said to have regularly consumed hashish, heroin and speed, died of a massive cerebral hemorrhage located in the region of the basal ganglia shortly after the intravenous administration of amphetamine and heroin. In the course of the post-mortem investigation, neither vascular malformations nor vasculitis could be detected in the brain. Even if the evidence for the existence of such alterations was missing, this does not exclude their presence for certain. Other potential amphetamine-induced vascular alterations are discussed.

Rationale: The issue of ecstasy-related fatalities has extensively attracted the attention of both the media and the general public, but less so of the scientific literature., Objectives: The aim of the present review is to focus on the epidemiological, clinical and pharmacological issues related to ecstasy fatalities., Results: Possibly due to a number of different reasons, the rates of ecstasy-related deaths seem to have peaked in recent years. MDMA metabolism is regulated by the levels of CYP2D6 and COMT (both exhibit some genetic polymorphism), and range of activity of these enzymes may account for some inter-individual differences in terms of toxic responses to the drug. A small increase in MDMA dosage can lead to a significant rise in drug plasma concentration. Due to their tolerance to MDMA psychoactive effects, some individuals may binge with dosages that may be the cause of serious concern. In experienced users, a reverse tolerance phenomenon can also be observed. Together with ecstasy, most of the misusers take a number of different compounds and the possible rationale of this style of consumption is commented upon here. Frequently, the lethal complications observed after acute MDMA administration can be the consequence of the occurrence of a serotonin syndrome and/or of sympathomimetic overstimulation (both conditions are exacerbated by environmentally induced overheating)., Conclusions: A number of methodological problems can contribute to making difficult the interpretation of the role played by ecstasy in so-called ecstasy-related deaths, especially so if accurate information is not available.

Objectives: To report the pathology, toxicology, cause, and manner of death in 3,4-methylenedioxymethamphetamine (MDMA)-associated fatalities in the United States. Although use trends are increasing, data regarding the hazards of MDMA are limited., Methods: The authors obtained fatality reports from participating medical examiners in the United States. Cases were identified as "drug-unrelated" when MDMA did not directly cause death (e.g., motor vehicle collision); deaths from drug toxicity were judged "drug-related.", Results: Thirty-eight (8%) of the surveyed medical examiners reported 102 deaths associated with MDMA use from 1999 to 2001. Ten percent of fatalities occurred in 1999 and 90% thereafter, representing a 400% relative increase. Victims tended to be young (mean age = 25), white (n = 87 [85%]), male (n = 70 [69%]), and otherwise healthy. Seventy-one (70%) deaths were drug-related (DR) and 31 (30%) were drug-unrelated (DU). Twenty-four (35%) DR deaths had a mean delay of 6.7 hours (95% CI = 5.1 to 8.2) in activating emergency medical services. Fifty-five DR cases (81%) were found in asystole and pronounced dead at the scene., Conclusions: The MDMA-associated fatal events typically occur in young, otherwise healthy individuals. MDMA's impact on the public health and safety of young adults and teenagers needs further assessment.

Aims: This study compares the hazard of death among opiate and amphetamine using clients who accessed drug treatment with individuals who had no specialist treatment contact between 1985 and 1998., Design, Setting, Participants: This was a retrospective cohort study of 4280 drug-using individuals (2887 opiate users, 1393 amphetamine users) admitted to Perth metropolitan hospitals or Perth psychiatric institutions between 1985 and 1998. Of these, 1469 attended Next Step Specialist Drug and Alcohol Services (928 received methadone and 541 attended counselling or support groups) and 2811 had no contact with this service., Methods: Data from two drug treatment programmes were linked with hospital morbidity, psychiatric services and the mortality database using record linkage., Findings: The results show that people who were currently in drug treatment had a lower hazard of death compared with non-clients and those who had ceased treatment. Those who had ceased treatment more than 6 months ago had 7.0 times the hazard of all-cause death and 8.4 times the hazard of drug-cause death. Opiate users were at 1.4 times the hazard of all-cause death and 2.4 times the hazard of drug-cause death compared with amphetamine users. Males were at 1.79 times the hazard of all-cause death and, unexpectedly, were found to be at 2.69 times the hazard of drug-cause death compared with females., Conclusions: Treatment protected clients from premature death compared with people who did not receive treatment and also those who ceased treatment. While amphetamine users had a lower risk of mortality compared with opiate users, the full extent of the relationship between amphetamine use and mortality needs to be examined further.

The present study reports on all deaths related to taking ecstasy (alone, or in a polydrug combination) occurring in England and Wales in the time frame August 1996-April 2002. Data presented here are based on all information recorded in the National Programme on Substance Abuse Deaths (np-SAD) database. The np-SAD regularly receives all information on drug related deaths in addicts and non addicts from coroners. A total of 202 ecstasy-related fatalities occurred in the chosen time-frame, showing a steady increase in the number of deaths each year. The ratio male:female was 4:1 and 3 of 4 victims were younger than 29. In 17% of cases ecstasy was the sole drug implicated in death and in the remaining cases a number of other drugs (mostly alcohol, cocaine, amphetamines and opiates) have been found. According to toxicology results, MDMA accounted for 86% of cases and MDA for 13% of cases; single deaths were associated with MDEA and PMA. This is the largest sample of ecstasy related deaths so far; possible explanations are given for the observed steady increase in ecstasy-related deaths and a tentative 'rationale' for this polypharmacy combination is then proposed., (Copyright 2003 John Wiley & Sons, Ltd.)