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Methamphetamine and cardiovascular pathology: A review of the evidence
Abstract
To examine the literature pertaining to the cardiovascular effects of methamphetamine and discuss the implications for methamphetamine users.
Relevant literature was identified through comprehensive MEDLINE and EMBASE searches.
There is sufficient clinical and experimental evidence to suggest that methamphetamine can have adverse and potentially fatal effects on the cardiovascular system. The existing literature suggests that: (1) methamphetamine users are at elevated risk of cardiac pathology; (2) risk is not likely to be limited to the duration of their methamphetamine use, because of the chronic pathology associated with methamphetamine use; (3) the risk of cardiac pathology is greatest among chronic methamphetamine users; (4) pre-existing cardiac pathology, due to methamphetamine use or other factors, increases the risk of an acute cardiac event; and (5) methamphetamine use is likely to exacerbate the risk of cardiac pathology from other causes, and may therefore lead to premature mortality.
... In the deceased, nephrosclerotic lesions were noted, raising the possibility of a correlation with extended methamphetamine usage over time. Individuals who chronically use methamphetamine may exhibit histopathological changes in their myocardium, particularly fibrosis, with myocardial fiber hypertrophy being one of these changes (Akhgari 2017;Kaye et al. 2007;Schürer 2017). In the cardiac histopathology of the presented case, focal contraction band necrosis and congestion were detected, which could not be attributed to chronic use. ...
... Methamphetamine exerts profound impacts on the cardiovascular system, giving rise to increased blood pressure, atherosclerosis, vasospasm, and the remodeling of cardiac tissue that can lead to arrhythmias and heart failure. There is evidence that methamphetamine is associated with the prolongation of QT intervals, consequently increasing the risk of initiating ventricular arrhythmias (Cruickshank and Dyer 2009; Al-Asmari 2021; Darke et al. 2017;Kevil et al. 2019;Nagasawa et al. 2018;Kaye et al. 2007). Potassium channel dysfunction in cardiac muscle cells is in question in acquired prolonged QT syndrome due to drug use. ...
... The use of multiple stimulant substances further increases the cardiac burden. If central nervous system depressants such as alcohol or opioids are taken together, it will be difficult to meet the increased need for cardiac oxygen demand associated with methamphetamine because they depress respiration, and the occasion for cardiac arrhythmia will be ready again (Darke et al. 2017;Kaye et al. 2007). ...
... This group of substances have a stimulating effect on the central nervous system with symptoms such as elevated blood pressure, heart rate and body temperature [2]. The use of stimulants is associated with cardiovascular problems such as arrhythmias, acute myocardial infarction, cardiomyopathy [3][4][5] and cerebrovascular events such as stroke [6,7]. The use is furthermore associated with numerous psychological effects such as paranoia, risk-taking behaviour, acute psychosis and suicide [2,8,9]. ...
... We examined organ weights that alone are of interest in the setting of acute or chronic drug intake, as such the lungs and brain are of interest [50], and in the perspective of chronic disease, the heart is of interest [3][4][5]21]. ...
Aims
To investigate the individual characteristics, causes and circumstances around deaths in stimulant use, and to examine how individuals who died with stimulants in their body differ from individuals who died with opioids in their body.
Methods
This study includes individuals who died during the years 2000–2018 and underwent a forensic autopsy at Forensic Medicine in Lund, Skåne County, Sweden. All individuals over 18 years of age with stimulants (n = 310), opioids (n = 2,039) or both stimulants and opioids (n = 385) in the body at the time of death, were included. The three groups were assessed regarding gender, age, place of death, BMI, other substances detected in forensic toxicological analysis, organ weights and underlying and contributing causes of death. The data were analysed by frequency and proportion calculations, cross-tabulations and comparisons of medians.
Results
The median age at death of the study population (n = 2,734) was 45.5 years (interquartile range ☯IQR] 32–60 years) and 73.2% were men. The most common cause of death in the stimulant group was suicide (26.8%), higher proportion compared to the opioid group (20.8%) (p = 0.017) and in the polysubstance group accidental poisoning (38.2%), higher proportion compared to the opioid group (18.0%) (p<0.001). Death by transport accidents was significantly associated with the stimulant group (p<0.001) as well as death by other accidents (p = 0.016).
Conclusions
Individuals who died with stimulants in their body died at a higher rate from suicide, transport accidents and other accidents, compared to individuals who died with opioids in their body. This study indicates the need to identify and prevent psychiatric conditions, elevated suicide risk, and risk-taking behaviors among people who use stimulants.
... Patients with psychiatric disorders are three-fold more likely to smoke (5) and have a higher burden of cardiometabolic risk factors including diabetes mellitus, hypertension, dyslipidemia, and obesity (6,7), and frequently have a dual diagnosis that refers to substance use disorder (SUD) (8). Substance abuse significantly increases morbidity and mortality, especially among cocaine, heroin, and amphetamine users (8)(9)(10)(11). During the past decade, there has been an increase in the number of patients with drug overdose who were fixated in the United States (US) (12). ...
... Approximately half of the patients with schizophrenia have a lifetime diagnosis of SUD (33). According to the literature, traditionally most CV mortality is caused by cocaine, heroin, and amphetamine use (8)(9)(10)(11). However, opioid overdose contributed to the decrease in the life expectancy of Americans from 78.8 to 78.5 between 2014 and 2017. ...
Introduction
Patients with mental disorders are at increased risk of cardiovascular events. We aimed to assess the cardiovascular mortality trends over the last two decades among patients with mental and behavioral co-morbidities in the US.
Methods
We performed a retrospective, observational study using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) Multiple Cause of Death dataset. We determined national trends in age-standardized mortality rates attributed to cardiovascular diseases in patients with and without mental and behavioral disorders, from 1999 to 2020, stratified by mental and behavioral disorders subtype [ICD10 codes F], age, gender, race, and place of residence.
Results
Among more than 18.7 million cardiovascular deaths in the United States (US), 13.5% [2.53 million] were patients with a concomitant mental and behavioral disorder. During the study period, among patients with mental and behavioral disorders, the age-adjusted mortality rate increased by 113.9% Vs a 44.8% decline in patients with no mental disorder (both p<0.05). In patients with mental and behavioral disorders, the age-adjusted mortality rate increased more significantly among patients whose mental and behavioral disorder was secondary to substance abuse (+532.6%, p<0.05) than among those with organic mental disorders, such as dementia or delirium (+6.2%, P− nonsignificant). Male patients (+163.6%) and residents of more rural areas (+128–162%) experienced a more prominent increase in age-adjusted cardiovascular mortality.
Discussion
While there was an overall reduction in cardiovascular mortality in the US in the past two decades, we demonstrated an overall increase in cardiovascular mortality among patients with mental disorders.
... The MA, known as a sympathomimetic agent, acts rigorously on the central and peripheral nervous systems and the cardiovascular system (7,8). The clinical signs depend on the duration, dose, and route of drug use. ...
... The vagus nerve is known as the major part of the autonomic nervous system and involves in the maintenance of homeostasis by the regulation of the neuroendocrineimmune axis and cardiovascular system (20,21). The disturbance of the balance between the sympathetic and parasympathetic nervous systems and overactivation of the sympathetic and immune systems have been reported in MUD (8,9). The current study hypothesizes the role of potential neuroprotective mechanisms of noninvasive vagus nerve stimulation (VNS) and the neurobiological pathways underlying the processes in the treatment of MUD. ...
: Methamphetamine (MA) use and the mortality it causes are increasing worldwide. The neurobiological mechanisms underlying the destructive effects of MA use are complex; however, there is much evidence that MA induces the dysfunction of monoaminergic transmission and causes oxidative stress, neuroinflammation, gliosis, and apoptosis. These toxic effects are associated with cardiotoxicity and neurotoxicity and with an imbalance in the autonomic nervous system, which altogether manifest themselves in clinical symptoms, such as neuropsychiatric disorders and cardiovascular diseases. There is no approved treatment for methamphetamine use disorder (MUD) despite all efforts made to date. The behavioral and pharmacological approaches currently used for the treatment of MUD are not completely effective. In this study, it is hypothesized that the stimulation of the vagus nerve and biological pathways underlying the processes of this stimulation might be effective as adjunctive therapy. Despite the potential effects of vagus nerve stimulation (VNS) to improve MUD, no study has yet examined the clinical potential effects of VNS in patients with the disorder. Therefore, further studies, including experimental and clinical trials, are needed to examine the effects of VNS on MUD.
... With overdose deaths escalating 1789% from 1999 to 2017 (Clink, 2017), the potent psychostimulant methamphetamine (METH) potentiates multiple mechanisms that lead to abuse potential and health harm. METH pushes biologic systems into hyperactivation, creating a spiral of dysfunction afflicting not only the central nervous system (CNS) (Kish, 2008) but also multiple cell and tissue types in the periphery (Martin et al., 1971;Kaye et al., 2007). Thereby, METH users experience a constellation of impairments ( Fig. 1) associated with the CNS and peripheral immune dysfunction, cardiovascular disease (Kaye et al., 2007), and immune dysregulation (Gaskill et al., 2014) involved in amplifying transmission of infectious disease (Galindo et al., 2012;Salamanca et al., 2015). ...
... METH pushes biologic systems into hyperactivation, creating a spiral of dysfunction afflicting not only the central nervous system (CNS) (Kish, 2008) but also multiple cell and tissue types in the periphery (Martin et al., 1971;Kaye et al., 2007). Thereby, METH users experience a constellation of impairments ( Fig. 1) associated with the CNS and peripheral immune dysfunction, cardiovascular disease (Kaye et al., 2007), and immune dysregulation (Gaskill et al., 2014) involved in amplifying transmission of infectious disease (Galindo et al., 2012;Salamanca et al., 2015). Direct effects of methamphetamine by self-evaluation include arousal, acute improvement of mood and cognition, increased blood pressure, and respiratory rate (Harris et al., 2003;Newton et al., 2005;Mendelson et al., 2006). ...
Methamphetamine (METH) is a potent psychostimulant that increases extracellular monoamines such as dopamine and norepinephrine and affects multiple tissue and cell types. The reinforcing properties of METH underlie its significant abuse potential and dysregulation of peripheral immunity and central nervous system functions. Together, the constellation of METH's effects on cellular targets and regulatory processes have shown to lead to immune suppression and neurodegeneration in METH addicts and animal models of METH exposure. Here we extensively review many of the cell types and mechanisms of METH-induced dysregulation of the central nervous system and peripheral immune system. Significance Statement Emerging research has begun to show that methamphetamine not only regulates dopaminergic neuronal activity, it also affects non-neuronal brain cells, such as microglia and astrocytes as well immunological cells of the periphery. The bi-directional communication between dopaminergic neurons in the CNS and peripheral immune cells becomes dysregulated by a constellation of dysfunctional neuronal and cell types revealing multiple targets that must be considered at the interface between basic and clinical neuroscience.
... The pathologic changes in the heart is well known in chronic methamphetamine abuse, including hypertrophy, interstitial fibrosis and microvascular disease [2][3][4][5]. Coronary artery disease and myocardial infarction, pulmonary hypertension, cardiomyopathy, or aortic dissection can occur in methamphetamine abusers, which can be fatal pathological findings to explain the cause of death. The pathophysiology is that catecholamine toxicity indirectly mediated by methamphetamine would cause endothelial and smooth muscle injuries, resulting in intimal hyperplasia of the coronary artery and myocardial injury as well as a direct effect on the cardiomyocytes [2,5]. ...
... These effects of methamphetamine also accelerate heart disease [2]. In case 1, the deceased had a hypertrophied heart with remodeling and coronary intimal fibrosis, a potentially fatal pathologic substrate that can lead to sudden death [2][3][4]. In case 2, focal interstitial and perivascular fibrosis was also observed in the myocardium, which could not be explained by other findings of the heart, including the normal heart weight and only mild stenosis of the coronary artery without any other medical history. ...
We present two cases of death associated with chronic methamphetamine abuse. Several findings were observed in chronic methamphetamine abuse; pathologic changes in the heart and coronary artery, pulmonary embolism by foreign materials (drug materials), small scars on the subcutaneous vein on the arms with skin infection and sepsis, and so on. These complications can be fatal pathological findings that explain sudden death. The toxicological test results should be carefully interpreted; the presence of methamphetamine in the toxicological results should not automatically be interpreted as acute intoxication. A meticulous postmortem examination with review of the scene, circumstances and past history is crucial in identifying these findings and interpreting them appropriately.
... In fact, prior research indicates that methamphetamine use may reduce traditional cardiovascular risk factors (e.g., obesity, cholesterol) due to its effects on appetite suppression [54]. However, methamphetamines are known to have cardiotoxic effects [55]. For example, methamphetamine use has direct and indirect effects on cardiovascular health through inflammatory and immunologic pathways and is associated with cellular and structural changes of the heart-increasing risk of for cardiac arrhythmias and cardiac myopathy [54]. ...
Background
Important gaps exist in our understanding of loneliness and biobehavioral outcomes among sexual minority men (SMM), such as faster HIV disease progression. At the same time, SMM who use methamphetamine are approximately one-third more likely than non-users to develop cardiovascular disease. This study examined associations of loneliness, stimulant use, and cardiovascular risk in SMM with and without HIV.
Method
Participants were enrolled from August 2020 to February 2022 in a 6-month prospective cohort study. The study leveraged self-report baseline data from 103 SMM, with a subset of 56 SMM that provided a blood sample to measure markers of cardiovascular risk.
Results
Loneliness showed negative bivariate associations with total cholesterol and LDL cholesterol in the cardiometabolic subsample ( n = 56). SMM with methamphetamine use ( t (101) = 2.03, p < .05; d = .42) and those that screened positive for a stimulant use disorder ( t (101) = 2.07, p < .05; d = .46) had significantly higher mean loneliness scores. In linear regression analyses, negative associations of loneliness with LDL and total cholesterol were observed only among SMM who used methamphetamine.
Conclusion
We observed lower cholesterol in SMM reporting loneliness and methamphetamine use. Thus, in addition to the observed associations of loneliness with cholesterol, there are important medical consequences of methamphetamine use including cardiovascular risk, higher HIV acquisition risk and progression, as well as stimulant overdose death. This cross-sectional study underscores the need for clinical research to develop and test interventions targeting loneliness among SMM with stimulant use disorders.
... In contrast, no overdose reversal medication is FDA-approved for psychostimulant or cocaine overdoses. Despite the lower mortality rates of methamphetamine and cocaine overdoses, these substances increase the risk of overdoses when used in combination with opioids by increasing the risk for cardiac arrest [29,30]. These biological influences may help explain why methamphetamine and cocaine use is associated with increased risk for overdoses among people who use opioids [31,32]. ...
Background
Over the past decade in the USA, increases in overdose rates of cocaine and psychostimulants with opioids were highest among Black, compared to White, populations. Whether fentanyl has contributed to the rise in cocaine and psychostimulant overdoses in Ohio is unknown. We sought to measure the impact of fentanyl on cocaine and psychostimulant overdose death rates by race in Ohio.
Methods
We conducted time series and spatiotemporal analyses using data from the Ohio Public Health Information Warehouse. Primary outcomes were state- and county-level overdose death rates from 2010 to 2020 for Black and White populations. Measures of interest were overdoses consisting of four drug involvement classes: (1) all cocaine overdoses, (2) cocaine overdoses not involving fentanyl, (3) all psychostimulant overdoses, and (4) psychostimulant overdoses not involving fentanyl. We fit a time series model of log standardized mortality ratios (SMRs) using a Bayesian generalized linear mixed model to estimate posterior median rate ratios (RR). We conducted a spatiotemporal analysis by modeling the SMR for each drug class at the county level to characterize county-level variation over time.
Results
In 2020, the greatest overdose rates involved cocaine among Black (24.8 deaths/100,000 people) and psychostimulants among White (10.1 deaths/100,000 people) populations. Annual mortality rate ratios were highest for psychostimulant-involved overdoses among Black (aRR = 1.71; 95% CI (1.43, 2.02)) and White (aRR = 1.60, 95% CI (1.39, 1.80)) populations. For cocaine not involving fentanyl, annual mortality rate ratios were similar among Black (aRR = 1.04; 95% CI (0.96,1.16)) and White (aRR = 1.02; 95% CI (0.87, 1.20)) populations. Within each drug category, change over time was similar for both racial groups. The spatial models highlighted county-level variation for all drug categories.
Conclusions
Without the involvement of fentanyl, cocaine overdoses remained constant while psychostimulant overdoses increased. Tailored harm reduction approaches, such as distribution of fentanyl test strips and the removal of punitive laws that influence decisions to contact emergency services, are the first steps to reduce cocaine overdose rates involving fentanyl among urban populations in Ohio. In parallel, harm reduction policies to address the increase in psychostimulant overdoses are warranted.
... Methamphetamine is cardiotoxic and increases heart rate and blood pressure when taken, resulting in a huge demand on the cardiovascular system [11]. Thus, the two most serious sequelae of methamphetamine use, cardiovascular and cerebrovascular complications, occur regardless of which delivery method is used [12][13][14][15]. Cumulative damage from long-term methamphetamine use significantly increases the risk of myocardial infarction in patients as they age [11]. ...
Methamphetamine addiction is a brain disease that causes abnormalities in the structure and function of the brain. EEG, a common signal acquired based on the noninvasive brain-computer interface, can reflect the altered brain activity associated with methamphetamine addiction. EEG-based analysis methods provide a perspective to explore the neural mechanisms of methamphetamine addiction and the effects on brain activity. This paper reports the results of a review of EEG-based assessment and classification of methamphetamine addiction. Current methods commonly used in EEG-based methamphetamine addiction research include traditional resting-state EEG analysis, brain network analysis, and analysis of event-related potentials. A small number of studies have classified methamphetamine addiction and healthy individuals based on resting state EEG features or event-related potentials. EEG is one of the common tools used to examine the effects of methamphetamine on brain function. In follow-up studies, new methods for analyzing resting-state EEG and event-related potentials may help to investigate the neural mechanisms of methamphetamine addiction.
... In the United States, this has been marked by a 50-fold increase in the number of overdose deaths involving amphetamines and a 5.6-fold increase in those involving cocaine over the past two decades [1]. Consistently ranked among the most harmful substances both to individuals and society [2,3], methamphetamine and cocaine have cardio-and neurotoxic properties [4][5][6][7] that substantially increase individuals' risks of experiencing physical and mental illness, including myocardial infarction, stroke, psychosis, and cognitive decline [8,9]. ...
Stimulant use among unstably housed individuals is associated with increased risks of psychiatric co-morbidity, violence, HIV transmission, and overdose. Due to a lack of highly effective treatments, evidence-based policies targeting the prevention of stimulant use disorder are of critical importance. However, little empirical evidence exists on risks associated with initiating or returning to stimulant use among at-risk populations. In a longitudinal cohort of unstably housed women in San Francisco (2016–2019), self-reported data on stimulant use, housing status, and mental health were collected monthly for up to 6 months, and factors associated with initiating stimulants after a period of non-use were identified through logistic regression. Among 245 participants, 42 (17.1%) started using cocaine and 46 (18.8%) started using methamphetamine. In analyses adjusting for demographics and socio-structural exposures over the preceding month, experiencing street homelessness was associated with initiating cocaine use (AOR: 2.10; 95% CI: 1.04, 4.25) and sheltered homelessness with initiating methamphetamine use (AOR: 2.57; 95% CI: 1.37, 4.79). Other factors—including race, income, unmet subsistence needs, mental health, and treatment adherence—did not reach levels of significance, suggesting the paramount importance of policies directed toward improving access to permanent supportive housing to prevent stimulant use among unstably housed women.
... An unbalanced Firmicutes/Bacteroidetes ratio is indicative of gut dysbiosis and is associated with various chronic diseases, such as obesity (Magne et al., 2020), inflammation (Stojanov et al., 2020), and hypertension (Yang et al., 2015). Interestingly, MUD patients are also a high-risk population for these diseases (Kaye et al., 2007;J Edge and Gold, 2011;Davidson et al., 2022). Even though it is challenging to determine a causal relationship, future studies should consider the potential role of the gut microbiota in the increased susceptibility to chronic illnesses among MUD patients. ...
Background
Methamphetamine use disorder (MUD) poses a considerable public health threat, and its identification remains challenging due to the subjective nature of the current diagnostic system that relies on self-reported symptoms. Recent studies have suggested that MUD patients may have gut dysbiosis and that gut microbes may be involved in the pathological process of MUD. We aimed to examine gut dysbiosis among MUD patients and generate a machine-learning model utilizing gut microbiota features to facilitate the identification of MUD patients.
Method
Fecal samples from 78 MUD patients and 50 sex- and age-matched healthy controls (HCs) were analyzed by 16S rDNA sequencing to identify gut microbial characteristics that could help differentiate MUD patients from HCs. Based on these microbial features, we developed a machine learning model to help identify MUD patients. We also used public data to verify the model; these data were downloaded from a published study conducted in Wuhan, China (with 16 MUD patients and 14 HCs). Furthermore, we explored the gut microbial features of MUD patients within the first three months of withdrawal to identify the withdrawal period of MUD patients based on microbial features.
Results
MUD patients exhibited significant gut dysbiosis, including decreased richness and evenness and changes in the abundance of certain microbes, such as Proteobacteria and Firmicutes. Based on the gut microbiota features of MUD patients, we developed a machine learning model that demonstrated exceptional performance with an AUROC of 0.906 for identifying MUD patients. Additionally, when tested using an external and cross-regional dataset, the model achieved an AUROC of 0.830. Moreover, MUD patients within the first three months of withdrawal exhibited specific gut microbiota features, such as the significant enrichment of Actinobacteria. The machine learning model had an AUROC of 0.930 for identifying the withdrawal period of MUD patients.
Conclusion
In conclusion, the gut microbiota is a promising biomarker for identifying MUD and thus represents a potential approach to improving the identification of MUD patients. Future longitudinal studies are needed to validate these findings.
... In fact, current use of either cannabis or METH is associated with conditions known to be associated with poorer COVID-19 outcomes such as tobacco smoking (Yen and Chong 2006;Badiani et al. 2015) and pulmonary conditions. Substance-specific risk factors include hesitancy to receive COVID-19 vaccine among cannabis users (Wolff et al. 2021;Schauer et al. 2021;Stack et al. 2021;Bolinski et al. 2022), and altered immune response to infection among METH users, rendering them subject to more severe and prolonged illness (Courtney and Ray 2014;Kaye et al. 2007;Kolaitis et al. 2021;Prakash et al. 2017). In contrast, a recent study reported that current cannabis users hospitalized with COVID-19 (n = 69) had better clinical outcomes compared with non-users, including a decreased need for ICU admission and mechanical ventilation (Shover et al. 2022). ...
Background
Poor outcomes of COVID-19 have been reported in older males with medical comorbidities including substance use disorder. However, it is unknown whether there is a difference in COVID-19 treatment outcomes between patients who are current cannabis users, excessive alcohol drinkers and those who use a known hazardous stimulant such as methamphetamine (METH).
Methods
Electronic medical records (EMR) of COVID-19 patients with current METH ( n = 32), cannabis ( n = 46), and heavy alcohol use ( n = 44) were reviewed. COVID-19 infection was confirmed by positive SARS-CoV-2 PCR test, current drug use was confirmed by positive urine drug testing, and alcohol use was identified by a blood alcohol concentration greater than 11 mg/dl.
Multivariate linear regression models as well as the firth logistic regression models were used to examine the effect of substance use group (METH, cannabis, or alcohol) on treatment outcome measures.
Results
A total of 122 patients were included in this analysis. There were no significant differences found between drug groups in regards to key SARS-CoV-2 outcomes of interest including ICU admission, length of stay, interval between SARS-CoV-2 positive test and hospital discharge, delirium, intubation and mortality after adjusting for covariates. About one-fifth (21.9% in METH users, 15.2% in cannabis users, and 20.5% in alcohol users) of all patients required ICU admission. As many as 37.5% of METH users, 23.9% of cannabis users, and 29.5% of alcohol users developed delirium ( P = 0.4). There were no significant differences between drug groups in COVID-19 specific medication requirements. Eight patients in total died within 10 months of positive SARS-CoV-2 PCR test. Two patients from the METH group (6.3%), two patients from the cannabis group (4.3%), and four patients from the alcohol group (9.1%) died.
Discussion
The study outcomes may have been affected by several limitations. These included the methodology of its retrospective design, relatively small sample size, and the absence of a COVID-19 negative control group. In addition, there was no quantification of substance use and many covariates relied on clinical documentation or patient self-report. Finally, it was difficult to control for all potential confounders particularly given the small sample size.
Conclusion
Despite these limitations, our results show that current METH, cannabis, and heavy alcohol users in this study have similar treatment outcomes and suffer from high morbidity including in-hospital delirium and high mortality rates within the first-year post COVID-19. The extent to which co-morbid tobacco smoking contributed to the negative outcomes in METH, cannabis, and alcohol users remains to be investigated.
... Methamphetamine (MA) is reported to be one of the most widely used drugs in the world, after cannabis, opium and other stimulants (UNODOC, 2019) and an increasing number of Chinese are using MA, with approximately more than half of all drug users were MA dependent patients in China (Commission, 2017). MA is highly addictive, and its abuse can lead to a variety of diseases including increased risk of HIV infection due to syringe sharing (Montoya et al., 2013;Parsons et al., 2013), cardiovascular disease (Kaye et al., 2007), cognitive impairment (Scott et al., 2007), and it can also lead to problems such as MAinduced psychosis due to oxidative stress and neurotoxicity (Trt Rungnirundorn et al., 2021). Currently, there are no effective methods to prevent and treat methamphetamine use disorder (MUD), suggesting that this critical public health issue requires further understanding. ...
Background
In patients with methamphetamine use disorder (MUD), antisocial personality disorder (ASPD) and alexithymia increase the risk of drug craving, but the relationship between the three of them is unclear. Therefore, this study explored the mediating role of alexithymia in the relationship between ASPD and drug craving.
Methods
We recruited 524 MUD patients at a drug rehabilitation center in Sichuan Province, China, and assessed ASPD with the Mini International Neuropsychiatric Interview (M.I.N.I.), methamphetamine craving with the Desire for Drugs Questionnaire (DDQ), and alexithymia with the Toronto Affective Disorder Scale (TAS-20).
Results
Compared with MUD patients without ASPD, MUD patients with ASPD had higher DDQ-desire and intention, DDQ-negative reinforcement and DDQ-total scores, as well as TAS-total and their subscale scores (all p < 0.05). Correlation analyses revealed a significant positive correlation between ASPD, alexithymia and drug craving. Mediating effect analysis further indicated that the relationship between ASPD and drug craving was mediated by alexithymia.
Conclusions
Our study demonstrates for the first time that alexithymia mediates the relationship between ASPD and drug craving, which may provide a new entry point for treating MUD with comorbid ASPD.
... The average age of 36 at the time of burn injury in this data signifies a low degree of comorbidities and risk factors for individuals developing ARDS, allowing isolation of amphetamine use and ARDS interaction. Most literature reports on the various cardiovascular effects of amphetamine [8] , but this study reviews an association with lung injury and amphetamine use. A lower APACHE II score and lower incidence of inhalational injury should correlate with lower ARDS. ...
Unlabelled:
A high incidence of adult respiratory distress syndrome (ARDS) is observed in patients with a history of amphetamine use with limited studies addressing this exact topic. The authors sought to understand and compare the clinical features of patients experiencing amphetamine-associated lung injury with features of similar patients naïve to amphetamines, in a population of burn patients. Patients in this population tend to be young with few comorbidities offering a unique opportunity to study the relationship between amphetamine use and ARDS.
Materials and methods:
A total of 188 patients age 18 and older with total body surface area (TBSA) between 20 and 60% were sampled over 5 years. To capture the moderate to severe burn population, a lower limit of 20% was chosen while 60% was used as the upper limit to exclude patients likely to die from the burns alone. Patients eligible to be include in the study had to meet the TBSA criteria. Demographic data was ascertained. Patients were placed into two cohorts: the amphetamine positive group (AmPOS), the amphetamine negative group (AmNEG). Key endpoints included hospital mortality, length of ICU stay, development of ARDS, and cardiac output parameters. Nonparametric data was evaluated with the Mann-Whitney test and categorical variables were compared using χ 2.
Results:
Data from 49 patients with ARDS were collected retrospectively out of the 188 patients in this TBSA range. The incidence of amphetamine abuse in these burn patients is 14.9%. The average age of AmPOS and AmNEG patients was 36 and 34 and the average TBSA of burns in the AmPOS and AmNEG group was 51.8 and 45.2%. The mean onset of ARDS was 2.2 days for the AmPOS versus 3.3 days for the AmNEG (P=0.19). At admission, patients with amphetamine use exhibited less inhalational injury and a lower Acute Physiology and Chronic Health Evaluation II (APACHE II) score. In AmPOS, 64% developed ARDS compared to 19% in AmNEG (P<0.001). Mortality, time on a ventilator, ICU days, packed Red Blood Cell, Fresh Frozen Plasm, platelets transfused, and initial cardiac parameters all were not statistically significant. On the initial date of ARDS diagnosis, there was no statistically significant difference with PaO2/FiO2 and compliance (P=0.67), but positive end expiratory pressure requirements was higher in AmPOS (P=0.018).
Conclusions:
Amphetamine Use was associated with increased risk of developing ARDS in the burn population. This is despite having a better APACHE II and lower incidence of inhalational injury in the AmPOS group, supporting amphetamine as an independent risk factor for ARDS.
... Infections such as bacterial, mycobacterial, fungal, syphilitis, lyme, septic emboli, mycotic aneurysm, HIV may cause CAAs with the mechanisms of direct invasion to arterial wall or induction of inflammatory response [16][17][18][19][20]. Use of drugs such as cocaine, amphetamine, protease inhibitors have been shown to be associated with CAAs. Presence of hypertension crisis and vasoconstriction by use of cocaine may lead to endothelial injury and aneurysmal formation [21,22]. In fibromascular dysplasia involvement of intimal, medial, adventitial, and periarterial layers in CAAs were evident [23]. ...
The terms coronary artery ectasia and coronary artery aneurysm are used to describe aneurysmal dilation of coronary arteries. Coronary artery aneurysms and ectasia are uncommon and frequently incidental finding in patients advised Coronary Angiography for coronary artery disease evaluation. Aneurysmal dilation of coronary arteries is observed in up to 5% of patients undergoing coronary angiography and are usually describe a localised dilatation of a coronary artery segment more than 1.5-fold compared with adjacent normal segments. Aneurysms and ectasia are associated with a vast group of disorders, and the evaluation and characterization of coronary aneurysms and ectasia represent a great diagnostic task with clinical and therapeutic implications. The underlying etiology is variable and includes degenerative, congenital, inflammatory, infectious, toxic, and traumatic causes. Causative factors include atherosclerosis, Takayasu arteritis, congenital disorders, Kawasaki disease (KD), and percutaneous coronary intervention. Due to their poorly elucidated underlying mechanisms, their variable presentations, and the lack of large scale outcome data on their various treatment modalities, coronary artery aneurysms and coronary ectasia pose a challenge to the managing clinician. Unlike aneurysms, ectasia is more frequently seen in association with atherosclerosis or as a compensatory mechanism in those cases in which a proximal stenosis is noted in the opposite coronary artery; ectasia is also seen in some coronary artery anomalies, such as anomalous origin from the pulmonary artery, or as a result of a high-flow state, as seen in coronary artery fistulas. The natural history of CAAs remains unclear; however, several recent studies have postulated the underlying molecular mechanisms of CAAs, and genome-wide association studies have revealed several genetic predispositions to CAA. Controversies persist regarding the. The diagnostic approach depends on the clinical scenario, and nowadays, noninvasive evaluation with multidetector computed tomography is possible. The purpose of this review is to summarize the present knowledge of CAAs and collate the recent advances regarding the epidemiology, etiology, pathophysiology, diagnosis, and to provide a succinct review of aneurysmal coronary disease, with a special emphasis on the challenges associated with its interventional treatment.
... 6 Chronic cardiovascular effects include methamphetamineassociated heart failure (MethHF). [6][7][8] Patient and societal impact of MethHF are increasingly recognised and reported in the literature. Compared with patients with heart failure (HF) without a history of MU (nonMethHF), patients with MethHF are younger with higher polysubstance use and psychiatric disorders. ...
Objective
To conduct a systematic review of observational studies on methamphetamine-associated heart failure (MethHF) .
Methods
Six databases were searched for original publications on the topic. Title/abstract and included full-text publications were reviewed in duplicate. Data extraction and critical appraisal for risk of bias were performed in duplicate.
Results
Twenty-one studies are included in the final analysis. Results could not be combined because of heterogeneity in study design, population, comparator, and outcome assessment. Overall risk of bias is moderate due to the presence of confounders, selection bias and poor matching; overall certainty in the evidence is very low. MethHF is increasing in prevalence, affects diverse racial/ethnic/sociodemographic groups with a male predominance; up to 44% have preserved left-ventricular ejection fraction. MethHF is associated with significant morbidity including worse heart failure symptoms compared with non-methamphetamine related heart failure. Female sex, methamphetamine abstinence and guideline-directed heart failure therapy are associated with improved outcomes. Chamber dimensions on echocardiography and fibrosis on biopsy predict the extent of recovery after abstinence.
Conclusions
The increasing prevalence of MethHF with associated morbidity underscores the urgent need for well designed prospective studies of people who use methamphetamine to accurately assess the epidemiology, clinical features, disease trajectory and outcomes of MethHF. Methamphetamine abstinence is an integral part of MethHF treatment; increased availability of effective non-pharmacological interventions for treatment of methamphetamine addiction is an essential first step. Availability of effective pharmacological treatment for methamphetamine addiction will further support MethHF treatment. Using harm reduction principles in an integrated addiction/HF treatment programme will bolster efforts to stem the increasing tide of MethHF.
... Although the efficacy of any particular treatment for managing psy- of chronic diseases such as heart disease [72] and pulmonary hypertension [73], overdose [3] and major psychiatric illness such as psychosis [74,75]. ...
It is estimated that a majority of people who use psychostimulants, particularly methamphetamine (MA) and cocaine, experience withdrawal upon abstinence from sustained use. This review of clinical research reports the evidence regarding biomedical and behavioral treatments for psychostimulant withdrawal symptoms. It provides a framework for clinicians and scientists to increase impact on attenuating MA and cocaine withdrawal during initial and sustained abstinence. Articles reviewed included reports of controlled clinical trials (randomized or non‐randomized) reporting at least one withdrawal symptom among the outcomes or specifically studying patients in withdrawal. Potential efficacy for MA withdrawal is noted for a few medications (mirtazapine, naltrexone, bupropion) and repetitive transcranial magnetic stimulation during acute (first week), early protracted (weeks 2‐4) and late protracted (>4 weeks) withdrawal phases. Topiramate shows mixed evidence of efficacy for cocaine withdrawal. In general, there is inconsistent signal for biomedical and behavioral treatments on MA and cocaine withdrawal.
... HR and BP were highest at baseline in our sample, and reduced throughout the admission. While a treatment approach utilising LDX has risks of short term excursions in SBP and HR, the benefit toward reducing future high-dose MA use outweighs these relatively minor risks (Kaye et al., 2007). ...
Background
There is no effective treatment for methamphetamine withdrawal. This study aimed to determine the feasibility and safety of a tapering dose of lisdexamfetamine for the treatment of acute methamphetamine (MA) withdrawal.
Methods
Open-label, single-arm pilot study, in an inpatient drug and alcohol withdrawal unit assessing a tapering dose of oral lisdexamfetamine dimesylate commencing at 250 mg once daily, reducing by 50 mg per day to 50 mg on Day 5. Measures were assessed daily (days 0-7) with 21-day telephone follow-up. Feasibility was measured by the time taken to enroll the sample. Safety was the number of adverse events (AEs) by system organ class. Retention was the proportion to complete treatment. Other measures included the Treatment Satisfaction Questionnaire for Medication (TSQM), the Amphetamine Withdrawal Questionnaire and craving (Visual Analogue Scale).
Results
Ten adults seeking inpatient treatment for MA withdrawal (9 male, median age 37.1 years [IQR 31.7 to 41.9]), diagnosed with MA use disorder were recruited. The trial was open for 126 days; enrolling one participant every 12.6 days. Eight of ten participants completed treatment (Day 5). Two participants left treatment early. There were no treatment-related serious adverse events (SAEs). Forty-seven AEs were recorded, 17 (36%) of which were potentially causally related, all graded as mild severity. Acceptability of the study drug by TSQM was rated at 100% at treatment completion. Withdrawal severity and craving reduced through the admission.
Conclusion
A tapering dose regimen of lisdexamfetamine was safe and feasible for the treatment of acute methamphetamine withdrawal in an inpatient setting.
... 27 Some of the conditions contributing to methamphetamine-related deaths include cardiovascular complications (eg, stroke, cardiomyopathy), HIV/AIDS, overdose, cancer and homicide. [28][29][30][31] There are also significant psychiatric consequences of methamphetamine use, namely higher risk of depression, anxiety, psychosis and suicide, especially among chronic users. 4 The impact of methamphetamine use on the health system extends from the health outcomes described previously. ...
Introduction
Rising use of methamphetamine is causing significant public health concern in Canada. The biological and behavioural effects of methamphetamine range from wakefulness, vigour and euphoria to adverse physical health outcomes like myocardial infarction, haemorrhagic stroke, arrhythmia and seizure. It can also cause severe psychological complications such as psychosis. National survey data point to increasing rates of methamphetamine use, as well as increasing ease of access and serious methamphetamine-related harms. There is an urgent need for evidence to address knowledge gaps, provide direction to harm reduction and treatment efforts and inform health and social policies for people using methamphetamine. This protocol describes a study that aims to address this need for evidence.
Methods
The study will use linked, whole population, de-identified administrative data from the Manitoba Population Research Data Repository. The cohort will include individuals in the city of Winnipeg, Manitoba, who came into contact with the health system for reasons related to methamphetamine use from 2013 to 2021 and a comparison group matched on age, sex and geography. We will describe the cohort’s sociodemographic characteristics, calculate incidence and prevalence of mental disorders associated with methamphetamine use and examine rates of health and social service use. We will evaluate the use of olanzapine pharmacotherapy in reducing adverse emergency department outcomes. In partnership with Indigenous co-investigators, outcomes will be stratified by First Nations and Métis identity.
Ethics and dissemination
The study was approved by the University of Manitoba Health Research Ethics Board, and access datasets have been granted by all data providers. We also received approval from the First Nations Health and Social Secretariat of Manitoba’s Health Information Research Governance Committee and the Manitoba Métis Federation. Dissemination will be guided by an ‘Evidence 2 Action’ group of public rightsholders, service providers and knowledge users who will ensure that the analyses address the critical issues.
... An estimated 29 million people, or 0.7% of the world's population aged between 15-64 years old, consumed amphetamine or methamphetamine (MA) in 2017 (hereafter referred to collectively as MA to reflect the most recent data on the context of the Australian market [1,2]). The use of MA has been associated with depression and anxiety, psychosis, suicidal behaviour, cardiovascular, respiratory and dermatological conditions, blood borne virus transmission, nonfatal injury as well as overdose and death [3][4][5][6]. The global, age-standardised rate of MA/ amphetamine dependence is estimated to be 96 people per 100,000 [7]. ...
Introduction
Methamphetamine (MA) use disorder is an important public health concern. MA withdrawal is often the first step in ceasing or reducing use. There are no evidence-based withdrawal treatments, and no medication is approved for the treatment of MA withdrawal. Lisdexamfetamine (LDX) dimesilate, used in the treatment of attention deficit hyperactivity disorder and binge eating disorder has the potential as an agonist therapy to ameliorate withdrawal symptoms, and improve outcomes for patients.
Methods
A single arm, open-label pilot study to test the safety and feasibility of LDX for the treatment of MA withdrawal. Participants will be inpatients in a drug and alcohol withdrawal unit, and will receive a tapering dose of LDX over five days: 250mg LDX on Day 1, reducing by 50mg per day to 50mg on Day 5. Optional inpatient Days 6 and 7 will allow for participants to transition to ongoing treatment. Participants will be followed-up on Days 14, 21 and 28. All participants will also receive standard inpatient withdrawal care. The primary outcomes are safety (measured by adverse events, changes in vital signs, changes in suicidality and psychosis) and feasibility (the time taken to enrol the sample, proportion of screen / pre-screen failures). Secondary outcomes are acceptability (treatment satisfaction questionnaire, medication adherence, concomitant medications, qualitative interviews), retention to protocol (proportion retained to primary and secondary endpoints), changes in withdrawal symptoms (Amphetamine Withdrawal Questionnaire) and craving for MA (visual analogue scale), and sleep outcomes (continuous actigraphy and daily sleep diary).
Discussion
This is the first study to assess lisdexamfetamine for the treatment of acute MA withdrawal. If safe and feasible results will go to informing the development of multi-centre randomised controlled trials to determine the efficacy of the intervention.
... Endothelial dysfunction is a hallmark prerequisite of cardiovascular complications including atherosclerosis, hypertension, myocardial infarction, and diabetes. METH can have adverse and potentially fatal effects on arteries and blood vessels, which contribute to increased blood pressure, inflammation and cardiovascular dysfunction including atherosclerosis [5][6][7]. METH also induces pro-inflammatory signaling responses and increases the production of reactive oxygen species that are detrimental to the cardiovascular system [8]. Thus, METH may lead to cardiovascular disease with endothelial dysfunction as a chief pathological mediator. ...
Methamphetamine (METH) is an addictive illicit drug used worldwide that causes significant damage to blood vessels resulting in cardiovascular dysfunction. Recent studies highlight increased prevalence of cardiovascular disease (CVD) and associated complications including hypertension, vasospasm, left ventricular hypertrophy, and coronary artery disease in younger populations due to METH use. Here we report that METH administration in a mouse model of ‘binge and crash’ decreases cardiovascular function via cystathionine gamma lyase (CSE), hydrogen sulfide (H2S), nitric oxide (NO) (CSE/H2S/NO) dependent pathway. METH significantly reduced H2S and NO bioavailability in plasma and skeletal muscle tissues co-incident with a significant reduction in flow-mediated vasodilation (FMD) and blood flow velocity revealing endothelial dysfunction. METH administration also reduced cardiac ejection fraction (EF) and fractional shortening (FS) associated with increased tissue and perivascular fibrosis. Importantly, METH treatment selectively decreased CSE expression and sulfide bioavailability along with reduced eNOS phosphorylation and NO levels. Exogenous sulfide therapy or endothelial CSE transgenic overexpression corrected cardiovascular and associated pathological responses due to METH implicating a central molecular regulatory pathway for tissue pathology. These findings reveal that therapeutic intervention targeting CSE/H2S bioavailability may be useful in attenuating METH mediated cardiovascular disease.
... Electrocardiography (ECG) Given the association of MA with autonomic nervous system dysfunction (74) and the significant difference in heart rate between drug-cue and neutral-cue in the cue-induced craving paradigm (75), ECG (BIOPAC ECG module, with sampling rate of 1,000 Hz) will be recorded in this experiment as an indicator of physiological changes. In addition, changes in the heart rate interval can reflect abnormalities of autonomic nervous function (76). ...
Background
Craving associated with drug-related memory is one of the key factors that induce the relapse of methamphetamine (MA). Disruption or modulation of the reconsolidation of drug-related memory may serve as an option for clinical treatment of MA addiction. This protocol proposes to use virtual reality (VR) to retrieve drug-associated memory and then use transcranial magnetic stimulation (TMS) at the neural circuit that encodes the reward value of drug cues to provide a non-invasive intervention during reconsolidation. We aim to evaluate the effectiveness of TMS treatment after VR retrieval on the reduction of cue reactivity and craving of MA.
Methods
This is a randomized, double-blind, sham-controlled, parallel group trial, targeting participants with MA use disorder aged from 18 to 45 years old. Forty-five eligible volunteers in Shanxi Drug Rehabilitation Center will be recruited and be randomly allocated into three parallel groups, receiving either 1) MA-related cues retrieval in VR combined with active TMS (MA VR scene + TBS) or 2) sham TMS (MA VR scene + sham TBS), or 3) neutral cues retrieval in VR combined with active TMS (neutral VR scene + TBS). Two sessions of post-VR-retrieval TBS will be scheduled on two separate days within 1 week. The primary outcome will detect the memory-related activity by the electroencephalography (EEG) reactivity to drug cues in VR scenes. Secondary outcomes are the self-reported MA craving in VR scene, the physiological parameter (cue-induced heart rate) and the scores of psychological questionnaires including anxiety, depression, and mood. All primary and secondary outcomes will be assessed at baseline, 1-week, and 1-month post-intervention. Assessments will be compared between the groups of 1) MA VR scene + TBS, 2) MA VR scene + sham TBS and 3) neutral VR scene + TBS.
Discussion
This will be the first study to examine whether the TMS modulation after VR retrieval can reduce self-reported craving and drug-related cue reactivity. It will promote the understanding of the neural circuit mechanism of the reconsolidation-based intervention and provide an effective treatment for MA use disorder patients.
Clinical Trial Registration
[Chinese Clinical Trial Registry], identifier [ChiCTR1900026902]. Registered on 26 October 2019.
... Of these four adolescents (Table 4), three had a larger HR increase between ECG intox and ECG reference than the mean HR increase (~40 bpm versus 12 bpm). In all four adolescents, there was an additional factor for QTc prolongation, namely, hypokalaemia (n = 1), hypocalcaemia (n = 2), hypernatremia (n = 1), acidosis (n = 2), metoclopramide (n = 1), and (meth)amphetamine intoxication [38]. Content courtesy of Springer Nature, terms of use apply. ...
In adults, alcohol intoxication is associated with prolongation of the QT interval corrected for heart rate (QTc). The QTc is influenced by age and sex. Although alcohol intoxication is increasingly common in adolescents, there are no data on the prevalence of QTc prolongation in adolescents with alcohol intoxication. This study aimed to determine the prevalence of QTc prolongation in adolescents with alcohol intoxication and identify at-risk adolescents. In this observational study including adolescents aged 10–18 years, heart rate and QT interval were automatically assessed from an electrocardiogram (ECG) at alcohol intoxication using a validated algorithm. The QTc was calculated using both the Bazett formula (QTc B ) and Fridericia formula (QTc F ). If present, an ECG recorded within 1 year of the date of admission to the emergency department was obtained as a reference ECG. A total of 317 adolescents were included; 13.3% had a QTc B and 7.9% a QTc F longer than the sex- and age-specific 95th-percentile. None of the adolescents had a QTc B or QTc F > 500 ms, but 11.8% of the adolescents with a reference ECG had a QTc B prolongation of > 60 ms, while no adolescents had a QTc F prolongation of > 60 ms. QTc prolongation was mainly attributable to an increase in heart rate rather than QT prolongation, which underlies the differences between QTc B and QTc F . Male sex and hypokalaemia increased the likelihood of QTc prolongation.
Conclusion : QTc prolongation was seen in approximately 10% of the adolescents presenting with alcohol intoxication, and although no ventricular arrhythmias were observed in this cohort, QTc prolongation increases the potential for malignant QT-related arrhythmias. Clinicians must be aware of the possibility of QTc prolongation during alcohol intoxication and make an effort to obtain an ECG at presentation, measure the QT interval, and give an adequate assessment of the findings. We advocate admitting adolescents with alcohol intoxication and QTc prolongation. During hospital admission, we recommend limiting exposure to QTc-prolonging medication, increasing potassium levels to a high-normal range (4.5–5.0 mmol/L) and obtaining a reference ECG at discharge.
What is Known: • One out of five deaths in adolescents is alcohol-related. Alcohol intoxication has been related to cardiac arrhythmias and sudden cardiac death . •In adults, alcohol intoxication is associated with QTc prolongation .
What is New: • Approximately 10% of the adolescents with alcohol intoxication had a QTc longer than the age- and sexspecific cut-off. In contrast to adults, in adolescents with alcohol intoxication, QTc prolongation is attributable to an increase in heart rate, rather than a prolongation of the QT interval. •Especially males and adolescents with hypokalaemia are at risk of QTc prolongation .
... For instance, van der Schoot, Ariens et al. (1962) reported that αethylamphetamine does not affect locomotion in mice, indicating a decreased potency compared to amphetamine. However, N , α-DEPEA may have similar adverse effects as methamphetamine in vivo, such as a high addiction potential, withdrawal symptoms after drug cessation, or cardiovascular and dental toxicity ( Kaye et al., 2007 ;Shetty et al., 2010 ;Simmler et al., 2013 ). Furthermore, N , α-DEPEA is a weak inhibitor of monoamine oxidase A (MAO-A). ...
3,4-methylenedioxyamphetamine (MDA) is a psychoactive compound chemically related to the entactogen MDMA. MDA shares some of the entactogenic effects of MDMA but also exerts stimulant effects and psychedelic properties at higher doses. Here, we examined the pharmacological properties of MDA analogs and related amphetamine-based compounds detected in street drug samples or in sport supplements. We examined the key pharmacological mechanisms including monoamine uptake inhibition and release using human embryonic kidney 293 cells stably transfected with the respective human transporters. Additionally, we assessed monoamine transporter and receptor binding and activation properties. MDA, its fluorinated analogs, as well as the α-ethyl containing BDB and the dimeric amphetamine DPIA inhibited NET with the greatest potency and preferentially inhibited 5-HT vs. dopamine uptake. The β‑methoxy MDA analog 3C-BOH and the amphetamine-based N,α-DEPEA inhibited NET and preferentially inhibited dopamine vs. 5-HT uptake. The test drugs mediated efflux of at least one monoamine with the exception of DPIA. Most compounds bound to 5-HT2A and 5-HT2C receptors (Ki ≤ 10 µM) and several substances activated the 5-HT2A and 5-HT2B receptor as partial or full agonists. Furthermore, several compounds interacted with adrenergic receptors and the trace amine-associated receptor 1 (TAAR1) in the micromolar range. The pharmacological profiles of some fluorinated and nonfluorinated MDA analogs resemble the profile of MDMA. In contrast, 3C-BOH and N,α-DEPEA displayed more pronounced dopaminergic activity similar to amphetamine. Pharmacokinetics and pharmacodynamics studies are necessary to better establish the risks and therapeutic potential of the tested drugs.
... Prescription psychostimulants fulfill many of the criteria for a suitable agonist medication. 9 However, the main concern with their maintenance was related to safety, considering illicit amphetamines use is associated with risk of cardiovascular 10 and neurological 11 events as well as adverse psychotic and mood symptoms. 12 Multiple studies and metanalyses have been conducted in the past decade, evaluating efficacy and safety profile of these medications, with generally favorable results. ...
... The European Monitoring Centre for Drugs and Drug Addiction noted rising rates of stimulant use such as amphetamine and methamphetamines between 2006 and 2014. 1 Stimulant use causes dilated cardiomyopathy via catecholamine-mediated effects such as tachycardia, hypertension, vasoconstriction, and direct cardio-toxic effects. 2,3 Up to one-third of patients with methamphetamineinduced cardiomyopathy have evidence of left ventricular (LV) thrombus formation. 4 However, the use of amphetamine and methamphetamines is associated with a preponderance of haemorrhagic rather than ischaemic stroke. ...
Background
Amphetamine use causes cardiomyopathy via catecholamine-mediated effects such as tachycardia, hypertension, vasoconstriction and direct cardio-toxic effects. Traditionally, an increased risk of haemorrhagic stroke is associated with amphetamine use. However, up to one-third of stimulant-associated cardiomyopathy patients have left ventricular thrombus formation leading to an increased risk of systemic embolization. We report a case of amphetamine induced cardiomyopathy complicated by embolic stroke secondary to left ventricular thrombus.
Case Summary
A 38-year-old man with six-month history of sustained amphetamine use presented to the emergency department with left sided weakness, facial droop and dysarthria. Angiography confirmed right middle cerebral artery thrombus. Prompt mechanical thrombectomy yielded full neurological recovery. Dyspnoea prompted transthoracic echocardiography showing dilated cardiomyopathy with an ejection fraction of 5% and left ventricular thrombus. Anticoagulation was initiated with warfarin as well as pharmacological therapy for heart failure with reduced ejection fraction including bisoprolol, spironolactone, loop diuretic and sacubitril/valsartan. He was discharged successfully following resolution of ventricular thrombus and medical management of heart failure. Clinical recovery was hampered by psychosocial factors resulting in non-adherence to medical therapy and continued amphetamine use.
Conclusion
Sustained amphetamine use can result in severe dilated cardiomyopathy with left ventricular thrombus formation and embolic complications such as ischaemic stroke. Avoidance of amphetamines in conjunction with guideline-directed pharmacological management are key components of therapy. However, psychosocial factors can exert significant influence on recovery.
... High, supra-therapeutic doses in illicit use stimulates microglial activation, neuroinflammation and displacement of dopamine from synaptic vesicles in dendrites, which increases oxidative stress and neuronal damage (Fleckenstein and Hanson G. R, 2009;Fleckenstein et al., 2000;Thomas et al., 2004). Sustained, frequent MA use also corresponds with development of cardiovascular disease (Darke et al., 2017;Kaye et al., 2007;Kevil et al., 2019), acute and chronic renal damage (Isoardi et al., 2019;Jones and Rayner, 2015), hepatic problems (Halpin et al., 2013;Koriem and Soliman, 2014), and psychiatric conditions and neurological alterations (Rusyniak, 2011;Salo et al., 2011;Sekine et al., 2001;Zweben et al., 2004). ...
Objective: This study tested the hypothesis that reported frequency of methamphetamine use is significantly associated with measures of social adversity, sexual risk behaviors, chronic health conditions, bacterial STIs and HIV-related factors among diverse men who have sex with men (MSM).
Methods: Data were 2,428 visits from 515 mSTUDY participants (261 people living with HIV; 254 HIV-negative). mSTUDY is an ongoing longitudinal study of racially/ethnically diverse MSM in Los Angeles County. Logistic regression with random intercepts modeled associations between self-reported past 6-month methamphetamine use (none, monthly or less, weekly or more) with reported adverse social outcomes (unemployment, housing instability, intimate partner violence), sexual risk behaviors, chronic health conditions, and biomarkers of bacterial STIs (chlamydia, gonorrhea, or syphilis) and detectable HIV viral load (among HIV-positive). Models controlled for confirmed HIV-serostatus.
Results: Prevalence of reported monthly or less methamphetamine use was 19%; weekly or more use was 18%. Multivariable models showed escalating odds of adverse social outcomes and sexual risk behaviors (p’s <.001) with increased methamphetamine use frequency. Frequency of methamphetamine use associated with increased odds of a positive bacterial STI test (p <.001), detectable viral load (in HIV-positive participants) (p <.001), renal condition (p =.047), neurological condition (p =.008), and psychological condition (p =.001).
Conclusions: Findings show cross-sectional links between reported methamphetamine use frequency and adverse social and health outcomes among MSM in Los Angeles and suggest there may be fewer social and physical health harms corresponding to less frequent use of methamphetamine in this group.
... METH use causes systemic toxicity, affecting immune function [10] and impairing the function of multiple organs [2]. A variety of medical complications have been related to METH use, such as tooth decay ('meth mouth') [11], pulmonary hypertension [12], hepatotoxicity [13], cardiovascular diseases and strokes [14,15], and blood-borne and sexually transmitted infections [16]. These complications may indicate physiological characteristics of premature aging process in METH users. ...
Methamphetamine (METH) use, most prevalent in young adults, has been associated with high rates of morbidity and mortality. The relationship between METH use and accelerated biological aging, which can be measured using leukocyte telomere length (LTL), remains unclear. We examined whether young adult METH users have shorter LTL and explored the relationship between characteristics of METH use and LTL by using Mendelian randomization (MR) analysis. We compared the LTL for 187 METH users and 159 healthy individuals aged between 25 and 34 years and examined the relationship of LTL with METH use variables (onset age, duration, and maximum frequency of METH use) by using regression analyses. In addition, 2-stage-least-squares (2SLS) MR was also performed to possibly avoid uncontrolled confounding between characteristics of METH use and LTL. We found METH users had significantly shorter LTL compared to controls. Multivariate regression analysis showed METH use was negatively associated with LTL (β = −0.36, P < .001). Among METH users, duration of METH use was negatively associated with LTL after adjustment (β = −0.002, P = .01). We identified a single nucleotide polymorphism (SNP) rs6585206 genome-wide associated with duration of METH use. This SNP was used as an instrumental variable to avoid uncontrolled confounding for the relationship between the use duration and LTL shortening. In conclusion, we show that young adult METH users may have shorter LTL compared with controls and longer duration of METH use was significantly associated with telomere shortening. These observations suggest that METH use may accelerate biological senescence.
Introduction
Use of amphetamine-type stimulants (ATS) contributes substantially to the global burden of disease. Large-scale follow-up studies of morbidity and mortality in ATS users are few. This study analysed morbidity, mortality, and potential predictors of all-cause mortality in a nationwide cohort of patients with ATS use disorder.
Methods
Data was acquired from national Swedish registers. All Swedish residents 18 years or older, with a registered ATS use diagnosis in 2013–2014 were included (N = 5,018) and followed until December 31, 2017. Comorbid diagnoses and causes of death were assessed and potential predictors of all-cause mortality were examined through Cox regression.
Results
Median age at inclusion was 36.6 years (interquartile range 27.4–––48.1) and 70.5 % were men. The crude mortality rate was 24.6 per 1,000 person-years. The adjusted all-cause standardized mortality ratio was 12.4 (95 % CI [11.34–13.55]). The most common cause of death was overdose (28.9 %). Multiple drug use (hazard ratio 1.39, 95 % CI [1.14–1.70], p = 0.004), anxiety (hazard ratio 1.39, 95 % CI [1.11–1.72], p = 0.014), viral hepatitis (hazard ratio 1.85, 95 % CI [1.50–2.29], p = 0.004), and liver disease (hazard ratio 2.41, 95 % CI [1.55–3.74], p = 0.004) were predictors of all-cause mortality.
Conclusions
Multiple drug use, anxiety disorders, viral hepatitis and liver diseases were identified as risk factors for death. Our findings call for better screening, prevention, and treatment of somatic and psychiatric comorbidity among ATS users to reduce mortality.
Stimulating and strengthening the endogenous motivation of abstinence is the key and prerequisite for the psychological withdrawal of synthetic drug addicts.At present, there is still a lack of systematic explanation framework for the endogenous motivation of abstinence.The article takes endogenous motivation as the starting point, combines endogenous and exogenous two-way perspectives, and based on in-depth interviews, the grounded theory research method, adopts the intensity sampling strategy, and takes typical drug addicts, successful drug addicts, and front-line policemen in drug rehabilitation centers under the jurisdiction of Fujian Province as the research objects to build an overall endogenous motivation resource exhaustion model for drug addicts.The research shows that: (1) the "four factor onion model" with lack of control, negative sense of life meaning, negative goal pursuit, passive cutting and expectation as the main body is the negative internal driving force for drug addicts to quit addiction.(2) The lack of sense of control is an important inducement for the lack of endogenous motivation to quit addiction, and the lack of external supervision of withdrawal mechanism may be one of the external reasons for the lack of sense of control.(3) The gradual improvement of family internal construction capacity and social support system can stimulate the endogenous motivation of abstinence and promote the reconstruction behavior of abstinence individuals.
Central stimulatory and hallucinogenic drugs of abuse like amphetamine and most congeners of amphetamine can have cardiac harmful effects. These cardiac side effects can lead to morbidities and death. In this paper, we review current knowledge on the direct and indirect effects of these amphetamine congeners on the mammalian heart—more specifically, the isolated human heart muscle preparation. In detail, we address the question of whether and how these drugs affect cardiac contractility and their mechanisms of action. Based on this information, further research areas are defined, and further research efforts are proposed.
As part of an interview-based qualitative study on the life-course of people who formally used methamphetamine in Aotearoa-New Zealand, this paper uses Deleuze and Guattari's rhizomatic perspective to trace the specific effects and particular relations involved in methamphetamine use. The methamphetamine-using trajectory for the 42 former users is a multifaceted and constantly fluctuating process involving multiple entries, exists, pathways, and restarts. By amplifying and enlightening the user, methamphetamine use begins by liberating desire through sending the user “out the gate,” but long-term high-dose use can end up constraining and repressing subjectivity and cyclically producing adverse psychological, emotional, interpersonal, and social effects. As a metamorphic process that produces transformative change, long-term high-dose methamphetamine use is a nonlinear rollercoaster ride that typically leads to a downward spiral whereby life stagnates, shrinks, or regresses. By undermining productive and transformative connections, the life of the long-term high-dose methamphetamine user typically—but not inevitably—involves revolving instead of evolving. Against a linear and deterministic popular media-generated narrative about methamphetamine use, a rhizomatic perspective emphasizes the potential for transformation by focusing upon the situational and interactional processes involved in users who undergo complex and varied temporary changes. From Deleuze and Guattari's perspective, disentangling from long-term high-dose methamphetamine use requires activating new relationships and possibilities for desire by forming meaningful biopsychosocial connections.
We measured the cardiac contractile effects of the sympathomimetic amphetamine-like drug methamphetamine alone and in the presence of cocaine or propranolol in human atrial preparations. For a more comprehensive analysis, we also examined the effects of methamphetamine in preparations from the left and right atria of mice and, for comparison, analyzed the cardiac effects of amphetamine itself. In human atrial preparations, methamphetamine and amphetamine increased the contractile force, the relaxation rate, and the rate of tension development, and shortened the time to maximum tension and the time to relaxation. Likewise, in mice preparations, methamphetamine and amphetamine increased the contractile force in the left atrium and increased the beating rate in the right atrium. The effect in human atrial preparations started at 1µM, therefore methamphetamine was less effective and potent than isoproterenol in increasing contractile force. These positive inotropic effects of methamphetamine were greatly attenuated by 10µM cocaine and abolished by 10µM propranolol. The inotropic effects of methamphetamine in human atrial preparations were associated with, and are believed to be mediated at least in part by, an increase in the phosphorylation state of the inhibitory subunit of troponin. In conclusion, the sympathomimetic central stimulant drug methamphetamine (as well as amphetamine) increased contractile force and protein phosphorylation, presumably through a release of noradrenaline in isolated human atrial preparations. Thus, methamphetamine acts as an indirect sympathomimetic in the human atrium.
Introduction:
Psychotropic drug-implicated (PDI) mortality-deaths in which psychotropic drugs were a contributing but not underlying cause of death-increased over 2 decades, with circulatory mortality as the primary cause leading to such deaths. Trends in PDI circulatory mortality over a 22-year period and its patterning in U.S. deaths are described.
Methods:
Deaths extracted from the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research Multiple Causes of Death database from 1999 to 2020 were analyzed to generate annual counts and rates for drug-implicated deaths due to diseases of the circulatory system, including by specific drug, sex, race/ethnicity, age, and state.
Results:
During a period when overall age-adjusted circulatory mortality rates declined, PDI circulatory mortality more than doubled, from 0.22 per 100,000 in 1999 to 0.57 per 100,000 by 2020, now representing 1 in 444 circulatory deaths. Although PDI deaths from ischemic heart diseases are proportionally aligned with overall circulatory deaths (50.0% vs 48.5%), PDI deaths from hypertensive diseases represent a larger proportion (19.8% vs 8.0%). Psychostimulants generated the greatest escalation for PDI circulatory deaths (0.029-0.332 per 100,000). The sex gap in PDI mortality rates widened (0.291 females, 0.861 males). PDI circulatory mortality is particularly notable for Black Americans and midlife Americans, with considerable geographic variability.
Conclusions:
Circulatory mortality with psychotropic drugs as a contributing cause escalated over 2 decades. Trends in PDI mortality are not evenly distributed across the population. Greater engagement with patients about their substance use is needed to intervene in cardiovascular deaths. Prevention and clinical intervention could contribute to reinvigorating previous trends of declining cardiovascular mortality.
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.
This qualitative life course-based study analyses the key circumstances preceding methamphetamine initiation. This paper utilizes Agnew’s “storylines” concept to analyse the background and situational factors that led 42 Aotearoa/New Zealanders to initiate methamphetamine. Multiple exposure to adversity across multiple life domains placed participants at heightened risk of early-onset drug use. Preceding methamphetamine initiation, the impact of social bonds and social roles were identified within the domains of family, romantic relationships, friendship and work. Whilst drug use onset broadly follows the stage theory sequence of drug use, participants did not initiate methamphetamine until age 27 on average. Initial use typically took place in a private setting among friends, family and co-workers. The initial effect was typically very positive, which greatly contributed to escalating use. Analysis revealed four main storylines, which highlight the importance of psychological state, social bonds, romantic attachments and social functioning in methamphetamine initiation.
There are global concerns about the proliferation and misuse of club drugs and novel psychoactive substances, yet we know little about their harms and research on clinical management and treatment remains limited. This book fills the knowledge gap by providing a detailed overview of the research evidence available to date. The book provides a framework that allows readers to understand this large number of new drugs, using classifications based on primary psychoactive effect. Within this framework, the book provides detailed reviews of the more commonly used drugs. Each chapter explores pharmacology, patterns and mode of use, acute and chronic harms, and clinical interventions supported by research evidence. An invaluable resource for clinical staff, this book will support clinicians working in the emergency department, substance misuse and addiction services, mental health services, primary care, sexual health services and more. It will also be of interest to academics and those developing drug policy.
Rates of stimulant use, including misuse of prescription stimulants and use of cocaine and methamphetamine, are rising rapidly among adolescents and young adults (“youth”). Stimulant misuse is associated with overdose, polysubstance use, substance use disorders, and other medical harms. Substance use is often initiated during adolescence and young adulthood, and interventions during these crucial years have the potential to impact the lifetime risk of stimulant use disorder and associated harms. In this narrative review, we review recent data on prescription and illicit stimulant use in youth. We describe the rising contribution of stimulants to polysubstance use involving opioids and other substances and to overdose, as well as ways to minimize harm. We also discuss prescription stimulant misuse, which is especially prevalent among youth relative to other age groups, and the limited evidence on potential pathways from prescription stimulant use to illicit stimulant use. Last, we assess potential strategies for the prevention and treatment of stimulant use disorder in youth.
Introduction: Methamphetamine use has been rising globally and results in significant morbidity and mortality. Methamphetamine is well known to affect multiple organs including neurological, cardiovascular, pulmonary, and renal. Cardiovascular manifestations like arrhythmias, pulmonary artery hypertension, cardiomyopathy, and cardiac arrest can occur from increased inflammation, myocardial fibrosis, and electrical remodeling.
Case Presentation: We present a rare case of a 39-year-old man with chronic methamphetamine abuse presenting with worsening shortness of breath and palpitations. Patient was eventually found to have acute onset left ventricular systolic dysfunction (ejection fraction 25-30%) from methamphetamine associated cardiomyopathy. He had a prolonged hospital course, however, a repeat echocardiogram performed 2 weeks later demonstrated near normal left ventricular function (ejection fraction 50-55%).
Conclusions: This case emphasizes the temporal effects of drug overdose on the cardiovascular system and its life-threatening complications. It is aimed at raising awareness about consideration of methamphetamine abuse as an important etiological factor when evaluating patients presenting with left ventricular systolic dysfunction and the importance of cessation of drug usage leading to reversal of cardiomyopathy.
We present the case of a 51-year-old male admitted for cardiovascular complications in the face of concomitant chronic methamphetamine and cannabis use. Upon further assessment, the patient exhibited cardiotoxicity, including acute to chronic congestive heart failure (CHF) exacerbation, hypercoagulable state, and electrolyte abnormalities. Cardiotoxicity secondary to chronic methamphetamine use has been established. However, marijuana's cardiovascular effects have not been well established. Even less information exists about the simultaneous use of methamphetamine and cannabis. With increasing interest in the use of marijuana for medical purposes, it is imperative to study any corresponding toxicity and adverse effect profile. The worldwide pattern of drug co-administration also brings the importance of this topic to light. This case report serves to provide insight into this information gap.
Methamphetamine (METH) abuse is a significant public health concern globally. Cardiac toxicity is one of the important characteristics of METH, in addition to its effects on the nervous system. However, to date, research on the cardiotoxic injury induced by METH consumption has been insufficient. To systematically analyze the potential molecular mechanism of cardiac toxicity in METH-associated heart failure (HF), a rat model was constructed with a dose of 10 mg/kg of METH consumption. Cardiac function was evaluated by echocardiography, and HE staining was used to clarify the myocardial histopathological changes. Integrated analyses, including mRNA, miRNA and lncRNA, was performed to analyze the RNA expression profile and the potential molecular mechanisms involved in METH-associated HF. The results showed that METH caused decreased myocardial contractility, with a decreased percent ejection fraction (%EF). Kyoto Encyclopedia of Genes and Genomes (KEGG) and (Gene Ontology) GO analyses of the RNAs with expression changes revealed abnormal circadian rhythm regulation in the METH groups, with circadian rhythm-related genes and their downstream effectors expressed differentially, especially the aryl hydrocarbon receptor nuclear translocator-like (Arntl). Competing endogenous RNA (ceRNA) networks associated with circadian rhythm, including Arntl, was also observed. Therefore, this study revealed that long-term METH consumption was associated with the HF in a rat model by decreasing the %EF, and that the abnormal circadian rhythm could provide new directions for investigating the METH-associated HF, and that the differentially expressed genes in this model could provide candidate genes for the identification and assessment of cardiac toxicity in METH-associated HF, which is fundamental for further understanding of the disease.
Substance use (SU) during pregnancy is on the rise, posing significant risks to the developing fetus. The adverse impact of maternal alcohol and nicotine use during the perinatal period on offspring health has been well established, including their associations with adverse cardiovascular health in offspring. However, limited studies examine the impact of other well-known SU utilized during pregnancy on offspring's cardiovascular health. This review summarizes the proposed mechanism of action of four commonly utilized substances: cocaine, marijuana, methamphetamine, and opioids, and their cardiovascular impact. Furthermore, we will review the current understanding of the adverse impact of substance use during pregnancy on offspring's cardiovascular system based on existing studies. This review will also highlight possible molecular mechanisms underlying the in-utero adverse programming of offspring's cardiovascular system secondary to SU in pregnancy and address the gaps in current understanding of how SU adversely impacts the developing cardiovascular system of offspring in utero.
The esports industry has grown exponentially and is expected to flourish rapidly in the coming years. Awareness about the cardiovascular sequalae in elite esport athletes has gained considerable momentum. Evidence supporting systematic screening in esport athletes is however lacking. In this narrative review, we discuss potential negative health effects on the cardiovascular system in esports enthusiasts. The pathophysiological mechanisms discussed in this narrative review may put esport athletes at an increased risk of cardiovascular events. Although large studies in esport athletes to substantiate these claims are inexistent, case reports or case-controlled studies have been included to support our hypotheses. Sleep deprivation, psychological stress, altered arterial stiffness, hypertension, and heart rate variability are some of these proposed mechanisms. The available data is unfortunately extrapolated from small cohorts. Nevertheless, the risk of sudden cardiac death is an important health concern which should be addressed appropriately. This review will raise awareness about the possible negative impact on the cardiovascular system in esport athletes.
Introduction
Although methylphenidate (MPH) used for treatment of attention deficit hyperactivity disorder (ADHD) are considered safe in healthy children and adolescents in the short and medium term, there is a widespread concern about long-term cardiovascular safety.
Material and methods
Interventional, prospective, longitudinal and comparative study with a crossover design to evaluate the cardiovascular impact of the treatment with MPH in healthy children and adolescents diagnosed with ADHD. A protocol for the cardiovascular evaluation was established at a basal point, after the first and the second year of the beginning with treatment based on the monitoring of blood pressure (BP) and echocardiographic follow-up of the systolic and diastolic functions, and structural cardiac properties.
Results
73 patients completed the study, with an average age of 9 ± 2.6 years, 75.3% were male and the majority were thin (64.4%). We found an increase in Systolic and Diastolic BP of 3.7 ± 9 mmHg (P = 0.004) and 2 ± 11,5 mmHg respectively. There were no severe cardiovascular events. We didn’t find any echocardiographic alterations namely on the structural properties or parameters of systolic function. Regarding diastolic function, a significant increase in the isovo-lumic relaxation time (IVRT) (P = 0.046) and deceleration time (P = 0.016) was observed. However, no significant alterations in the parameters related to distensibility of the LV neither in the early diastolic pressure were found.
Conclusion
Further studies are needed to evaluate the impact of psychostimulants as a modifiable long-term Cardiovascular Risk Factor.
Objective
This study aims to examine the effects of methamphetamine (MA) use and dependence and MA withdrawal symptoms on the telomere length and whether shortening of the latter is associated with MA-induced psychosis (MIP).
Methods
This study included 185 MA-abuse, 118 MA-dependent, and 67 MIP patients, diagnosed using DSM-IV criteria. The Semi-structured Assessment for Drug Dependence and Alcoholism (SSADDA) questionnaire was employed to collect MA-related data. MIP was confirmed using the Methamphetamine Experience Questionnaire (MEQ). The leukocyte telomere length was measured using real-time polymerase chain reaction measuring the Telomere/Single gene ratio (T/S ratio). Data were analyzed using multivariate statistical analyses.
Results
There were no significant associations between the T/S ratio and severity of MA-use, MIP, and MA withdrawal symptoms. MIP was significantly predicted by alcohol dependence, antisocial personality disorder, and MA-use severity. There were significantly positive associations between the T/S ratio and previous traumatic and life-threatening events. The T/S ratio was not affected by alcohol and nicotine dependence. Alcohol and nicotine dependence, antisocial personality disorder, and severity of MA use increased risk of MA withdrawal symptoms.
Conclusion
MIP and MA-use severity are not associated with leukocyte telomere length, but previous traumatic and life-threatening events are associated with increased telomere length.
This study assessed the effects of aerobic exercise on cardiac autonomic nervous system function (based on heart rate variability [HRV]) and executive function among individuals with methamphetamine use disorder (MUD). We further examine the role of autonomic nervous system control in aerobic exercise (assessed via cardiopulmonary fitness) and executive function. A total of 330 individuals with MUD were randomly divided into exercise (n = 165) and control (n = 165) groups, who underwent eight-week aerobic exercise/health education program consisting of five 60–minute sessions a week. The outcome measures included cardiopulmonary fitness, HRV time-domain and frequency-domain parameters, and executive function. Our statistical analyses comprised repeated-measures analyses of variance, correlation analyses, and mediation and moderation effect tests. The results indicated that aerobic exercise could simultaneously improve autonomic nervous system function and executive function among individuals with MUD. Moreover, the changes in cardiopulmonary fitness, high frequency HRV, and executive function were positively correlated. HRV did not significantly mediate the relationship between aerobic exercise and executive function; however, it did have a moderating effect, which was eliminated after adjusting for demographic and drug-use covariates. Among the covariates, age was the greatest confounder and was inversely proportional to cardiopulmonary function, HRV, and executive function. Cardiac autonomic nervous system function exerted a moderating, rather than a mediating, effect on the relationship between aerobic exercise and executive function. However, this potential effect was largely influenced by covariates, particularly age.
Synthetic drug use (SDU) is on the rise in China. Utilizing a grounded three-level social-ecological theoretical model, we aim to better understand how users, medical professionals, and other community gatekeepers perceive the causes and consequences of synthetic drug use in Kunming, China. Past work typically relies on drug users confined to rehabilitation facilities. Utilizing qualitative methods, our work integrates how various community actors perceive problems around synthetic drug use. Thirty face-to-face interviews were conducted in Kunming that were audio-recorded and transcribed. We identify emergent personal, interpersonal and societal level themes shaping SDU which provided our grounded theoretical model. Regardless of their social position, informants identified curiosity, peer networks that facilitated exposure, and the communality of sharing the drug experience as reasons to try synthetic drugs. Drug users reported negative consequences of SDU including the inability to sleep, a fear that others might discover one was using, and the difficulty of quitting. Medical professionals and others in the community were more likely to identify potential harms of SDU. Still, these community members felt synthetic drugs were less problematic than traditional drugs and reported less prejudice and stigma about these new drugs. Overall, medical professionals felt ill-prepared to deal with this new epidemic.
The smoking of crystal methamphetamine, or "ice," is a growing drug abuse problem in the United States. The toxic effects of methamphetamine smoking have not been well described. We describe two patients with cardiovascular toxic effects associated with the smoking of crystal methamphetamine. In our first patient, the use of smokable methamphetamine was associated with the subsequent development of pulmonary edema and a dilated cardiomyopathy. In our second patient, the smoking of crystal methamphetamine likely produced diffuse vasospasm that resulted in acute myocardial infarction, cardiogenic shock, and death. The recognition of potentially lethal cardiac complications associated with the smoking of crystal methamphetamine is of extreme significance and should be emphasized to potential abusers of this drug.
(JAMA. 1991;265:1152-1154)
During the past several years, the use of a smokable form of methamphetamine hydrochloride called "ice" has increased rapidly. The heaviest use has occurred on the West Coast and in Hawaii. Many regional emergency departments treat more methamphetamine users than cocaine-intoxicated patients. The ease of synthesis from inexpensive and readily available chemicals makes possible the rampant abuse of a dangerous drug that can produce a euphoria similar to that induced by cocaine. Clinicians should be familiar with the medical effects and treatment of acute methamphetamine toxicity.
Amphetamines remain a popular illicit drug among young adults in Australia and a number of other countries, particularly by injection. A significant increase in the number of people presenting to drug treatment services with a primary amphetamine problem in Australia and the US has occurred in recent years. A survey of 200 regular amphetamine users was conducted in Sydney to determine the treatment issues and preferences of this population. Substantial harm associated with the use of this drug was found, most notably psychological problems, physical health problems, dependence and financial problems. A perceived need for amphetamine-specific treatment was evident. Popular treatment options requested by users included pharmacotherapies, natural therapies and counselling. While regular amphetamine users can attend existing treatment services, the efficacy of these treatments for amphetamine problems has not been evaluated. There is also a need to develop and evaluate amphetamine-specific interventions in order to attract this population into treatment.
A 51-year-old man suddenly collapsed while being arrested. He was an abuser of methamphetamine (MP) with a history of previous convictions. The blood MP concentration at autopsy was below the lethal level. The heart revealed hypertrophy and endocardial thickening of the bilateral ventricles. On microscopic examination, the typical findings of hypertrophic cardiomyopathy were not seen, however endocardial thickening with increasing elastic fibres was seen in all the ventricles and in the atria. In the conduction system, the AV node artery with luminal narrowing was longitudinally compressed by circumferential tissue. Severe interstitial fibrosis and small scar formation of the superior ventricular septum were also seen. In addition, diffuse hypertensive pulmonary arteriopathy was seen in the lung parenchyma.
We surmise that the AV node artery had been chronically compressed by the circumferential architecture, due to a chronic increase in intracardiac pressure. We believe that the pathological lesions noted in both the cardiac conduction system and the lung in our case may be a complication of MP abuse, and that an MP abuser with such lesions could easily die suddenly upon experiencing emotional stress.
To outline the recent features of methamphetamine-related fatalities from the medico-legal point of view, a retrospective investigation of forensic autopsy cases involving methamphetamine during a 5-year period (1994–1998) in the southern half of Osaka city and surrounding areas (about 1.57 million population) was undertaken. Among 646 autopsy cases, methamphetamine was detected in 15 victims (nine males, six females; 16–71 years of age; most frequently in males in their thirties). Primary scenes of fatal events were concentrated in the middle of the city. About half of them were transfered from emergency medical centers (survival time, up to 30 h). The cause and manner of death were: methamphetamine poisoning (n=4), homicide (n=4), accidental falls and aspiration from drug abuse (n=4), fire death (n=1), myocardial infarction (n=1), and cerebral hemorrhage (n=1) under drug influence. Usually injection scars and fresh puncture sites were found. Blood methamphetamine concentrations were 2.29–17.05 μmol/dl in the fatal poisoning, 0.44–3.80 μmol/dl in deaths from other extrinsic causes (trauma), and 1.35–2.17 μmol/dl in cardio- and cerebrovascular strokes. Common complications were cardiomyopathy, cerebral perivasculitis and liver cirrhosis/interstitial hepatitis. Fatal and nonfatal methamphetamine poisonings are separately dealt with by the administrative medical examiner’s office and in emergency medical centers. Tightly cooperative approaches of clinical and medico-legal experts are required for the effective social and medical management of drug abuse.
A 45-year-old woman with congestive heart failure, in whom there was no evidence of coronary heart disease, valve disease, or other demonstrable cause of heart failure, was found to have taken high doses of dextroamphetamine over a long period. Withdrawal of amphetamine resulted in deterioration, suggesting a physical cardiac dependence on the drug. The clinical and autopsy findings are presented and the similarities to the myocarditis associated with pheochromocytoma are discussed. The evidence presented suggests a causal relationship between administration of dextroamphetamine and the cardiomyopathy.
Postmortem findings in 25 intravenous addicts of centrally stimulating amines and centrally depressive narcotics (opiates) have been analysed with special reference to the presence of pathologic findings in the heart, and the cause of death. Most cases exhibited myocardial lesions of varying age, consistent with various phases of myofibrillar degeneration, such as hemorrhages, contraction bands, focal necroses, granulation tissue, stromal condensation, and scarring, indicating an active chronic process in the myocardium and the subendocardium, with a bias toward the conduction system of the heart. The lesions have been found in drug addicts who died immediately following an injection of narcotics as well as in those who, irrespective of their drug influence, have died following intervening injuries or disease. Cardiac lesions in drug addicts seem to have a variety of causative factors: infections, toxic influence, hypersensitivity, influence of catecholamines and general hypoxia. The authors feel that the two latter suggested causes appear most regularly and deserve special attention. The significance of these heart lesions seems to vary, but at times they may be the determining factor in the fatal outcome of a case.
The world medical literature contains 43 reports of deaths associated with amphetamines in a 35-year period. These included seven cerebrovascular accidents, six sudden cardiac deaths, three cases of hyperpyrexia, eight poisonings of uncertain mechanism and seven cases of medical complications of intravenous injection; the remainder were of uncertain cause. In contrast, in Ontario alone, in 1972 and 1973 there were 26 deaths in amphetamine users, of which 16 were due to accident suicide or homicide. Of the remaining cases, two were cardiac, two hepatic and the rest were mixed drug overdose. Pulmonary granulomata, subacute hepatitis and other lesions resulting from intravenous drug use were common findings at autopsy. On the basis of the estimated number of regular users of intravenous amphetamine in Ontario, the mortality rate in such users is at least four times as high as in the general population of the same age, and is comparable to that in alcoholics and heroin addicts. However, the absolute number of alcohol-related deaths is far greater than the number of deaths in amphetamine or heroin users.
The effects of methamphetamine were studied on cardiovascular function in conscious squirrel monkeys. Methamphetamine (0.1-3.0 mg/kg, IV) produced a dose-dependent increase in blood pressure. Its effects on heart rate were more complex, with lower doses (0.1-0.3 mg/kg) producing increases in heart rate and higher doses (1.0-3.0 mg/kg) producing decreases. To determine the pharmacological mechanisms involved in methamphetamine's effects, a number of drugs were tested as pretreatments to an injection of 0.2 mg/kg methamphetamine. This dose produced the maximal heart rate increase. The alpha 1-antagonist prazosin completely antagonized the effects of methamphetamine on blood pressure, while the nonselective beta-antagonist propranolol and beta 1-selective antagonist atenolol completely antagonized the tachycardiac effect of methamphetamine. The dopaminergic antagonists SCH 23390 and haloperidol antagonized some of the cardiovascular effects of methamphetamine. These results indicate that the pressor and tachycardiac effects of methamphetamine are mediated via alpha 1- and beta 1-adrenoceptor mechanisms, respectively. Dopaminergic mechanisms are also involved in methamphetamine's cardiovascular effects.
Three typical cases of acute methamphetamine intoxication are reported. The concentrations of methamphetamine in the blood were 27.2, 6.43 and 0.60 micrograms/ml, respectively. All three victims had been exposed to high temperature in a bathroom or a closed room in summer at the time of death. Macroscopic autopsy revealed hemorrhagic pulmonary edema, and histologically, diffuse contraction-band necrosis was evident in the myocardium in all cases. The absolute structures of six illegally available methamphetamine showed an (S)-configuration with an optical purity of > 99% in enantiomeric excess and four were racemic form.
It is now well documented that both cocaine (Coc) and methamphetamine (Meth) are independently capable of inducing injurious effects on the adult and developing myocardium. In addition, when these drugs are used concomitantly such as in polydrug abuse, it has been suggested that they may cause synergistic adverse effects on the myocardium. In this investigation, primary myocardial cell cultures were established from 3-5-day-old Sprague-Dawley rats to describe the adverse effects of Coc and Meth on the myocardium. After the cells were in culture for 4 days, they were exposed to 1 x 10(-5) and 1 x 10(-3) M Coc alone; 1 x 10(-5) and 1 x 10(-3) M Meth alone; and combinations of 1 x 10(-3) M Coc with 1 x 10(-5) M Meth and 1 x 10(-5) M Coc with 1 x 10(-5) M Meth. Lactate dehydrogenase (LDH) release, morphology, and beating activity were evaluated after exposure to the drugs for 1, 4 and 24 h. With all treatment groups for the first 4 h, LDH release was not significantly different from untreated controls. Significant LDH release (P less than 0.001) was exhibited at 24 h with 1 x 10(-3) M Coc alone, 1 x 10(-3) M Meth alone, and 1 x 10(-3) M Coc with 1 x 10(-5) M Meth. For 24 h of treatment, cellular injury (pseudopodia, vacuolization, granulation) induced by 1 x 10(-3) M and 1 x 10(-5) M Coc alone was extensive and minimal, respectively. When 1 x 10(-5) M Meth was added with 1 x 10(-5) M Coc, pseudopodia formation was extensive. No measurable beating activity was observed at 1, 4 and 24 h exposure to 1 x 10(-3) M Coc alone and 1 x 10(-3) M Coc with 1 x 10(-5) M Meth. At 1 h, beating activity after treatment with 1 x 10(-5) M Coc alone and 1 x 10(-5) M Meth alone was not significantly different from untreated controls; however, the percentage of areas exhibiting contractile activity was depressed. Addition of Meth (1 x 10(-5) M) potentiated Coc-induced (1 x 10(-5) M) depression of contractile activity at all 3 time-points. These data suggest that Coc and Meth may interact synergistically at the cellular level to directly potentiate injury to postnatal myocardial cell cultures.
The purpose of this study was to determine the cerebral regional microvascular and vascular responses to amphetamine sulfate at a dose (5 mg/kg) known to affect neuronal function. Cerebral blood flow (14C-iodoantipyrine method) and percent of perfused capillaries (fluorescein isothiocyanate-dextran and alkaline phosphatase staining method) were determined during control and after intravenous administration of amphetamine in conscious Long-Evans rats. Amphetamine caused an increase in blood pressure (34%) and heart rate (31%). There was a significant increase in averaged cerebral blood flow from 98 +/- 8 to 166 +/- 9 ml/min/100 g after amphetamine. This flow increase was significant in the cortex, basal ganglia, pons and medulla, however the increase was not significant in the hypothalamus. In control rats, there were approximately 325 +/- 17 capillaries/mm2 of brain tissue and 52 +/- 1% of them were perfused. Amphetamine increased the percent perfused significantly to 72 +/- 1% in all examined regions. There was a similar significant increase in the percent of perfused cerebral capillary volume fraction. There were both vascular and microvascular responses to amphetamine, increasing cerebral blood flow as well as reducing the diffusion distance for oxygen.
This study investigated alterations in the disposition and pharmacodynamics of methamphetamine HCl after daily administration. Six male paid volunteers familiar with the use of amphetamines participated. Each subject was administered 10 mg of methamphetamine HCl as a slow-release preparation (Desoxyn Gradumets) at 9 a.m. for 13 consecutive days (days 2-14 of the study). On days 1 and 15 the subjects were challenged with 10 mg of oral deuterated methamphetamine HCl. Deuterated drug was used to differentiate plasma concentrations of challenge doses from those of daily doses. The heart rate, subjective perception of "high," and plasma concentrations of methamphetamine were examined on days 1 and 15. Repeated ANOVA measures indicate that a significant decrease in heart-rate acceleration in response to methamphetamine challenge occurred on day 15 [F(1,5) = 8.26, p less than or equal to 0.035]. However, no significant change in either the subjective ratings of "high" or the plasma concentrations of deuterated methamphetamine occurred. These findings indicate that the disposition of methamphetamine and its subjective effects were not altered by this period of daily exposure to a low dose of the drug. In contrast, tolerance to the heart-rate accelerating effect was observed.
The smoking of crystal methamphetamine, or "ice," is a growing drug abuse problem in the United States. The toxic effects of methamphetamine smoking have not been well described. We describe two patients with cardiovascular toxic effects associated with the smoking of crystal methamphetamine. In our first patient, the use of smokeable methamphetamine was associated with the subsequent development of pulmonary edema and a dilated cardiomyopathy. In our second patient, the smoking of crystal methamphetamine likely produced diffuse vasospasm that resulted in acute myocardial infarction, cardiogenic shock, and death. The recognition of potentially lethal cardiac complications associated with the smoking of crystal methamphetamine is of extreme significance and should be emphasized to potential abusers of this drug.
Jeffrey L. Anderson, Cynthia D. Adams, Elliott M. Antman, Charles R. Bridges, Robert M. Califf, Donald E. Casey, William E. Chavey, Francis M. Fesmire, Judith S. Hochman, Thomas N. Levin, A. Michael Lincoff, Eric D. Peterson, Pierre Theroux, Nanette Kass Wenger, R. Scott Wright, Sidney C. Smith, Alice K. Jacobs, Cynthia D. Adams, Jeffrey L. Anderson, Elliott M. Antman, Jonathan L. Halperin, Sharon A. Hunt, Harlan M. Krumholz, Frederick G. Kushner, Bruce W. Lytle, Rick Nishimura, Joseph P. Ornato, Richard L. Page, Barbara Riegel. (2007) ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction. Journal of the American College of Cardiology 50, e1-e157
CrossRef
Development of an acute myocardial infarction is described in two previously healthy men of 25 and 40 years respectively, shortly after taking oral amphetamine derivatives. Coronary angiography disclosed in both men a normal coronary system without stenoses or irregularities. Ventriculography revealed in both a segmental dysfunction of the left ventricle. A relationship is postulated between use of amphetamine and occurrence of acute myocardial infarction in the absence of coronary artery disease.
A man aged 27 years presented with an acute myocardial infarction after injecting himself intravenously with amphetamine. Soon after admission ventricular fibrillation developed. This was successfully cardioverted. Coronary arteriography was normal.
This brief report details the case of a woman who was thought, after extensive evaluation, to have idiopathic congestive cardiomyopathy. It was subsequently found that systolic ventricular dysfunction was due to amphetamine abuse, and that ventricular function normalized after discontinuation of this drug.
A single intraperitoneal injection of methamphetamine hydrochloride (10 mg/kg) given to rats in a warm (30 degrees C) and humid environment caused an uncommon form of cardiac lesion during the first few hours. Disseminated loss of myoglobin was demonstrated immunohistochemically in the ventricular myocardium. Ultrastructurally, the myocardial cells with myoglobin loss were characterized by the presence of swollen mitochondrial and packed cellular constituents, but showed no cytoplasmic edema. Sarcolemmal damage was also noted by freeze-fracture electron microscopy. It was considered that the mitochondrial dysfunction was the first alteration to appear in the myocardial cells, and that this finally led to sarcolemmal rupture.
We present a retrospective study of 127 cases of amphetamine toxicity in an emergency department (ED). The most common presenting symptoms seen were agitation, hallucinations, suicidal behavior, and chest pain. Toxicologic analysis showed amphetamines are generally not mixed with other stimulants. The vast majority of patients did not require pharmacologic treatment in the ED. Thirteen patients (10%) required admission to the hospital. Toxic medical effects of amphetamine-related compounds seen in our patients are discussed.
Cocaine- and methamphetamine-related homicides and fatal accidental overdoses in San Diego County were studied retrospectively for the 1987 calendar year. Cocaine was involved in 66 cases (39 homicides, 27 accidental overdoses), methamphetamine in 32 cases (23 homicides, 9 accidental overdoses), and a combination of cocaine and methamphetamine in 10 cases (4 homicides, 6 accidental overdoses). The composite for cocaine-related deaths was a 30-year-old black man in whom was also found at least 1 other drug, usually ethanol or morphine. The composite for methamphetamine-related deaths was a 32-year-old Caucasian man who used methamphetamine with at least 1 other drug (usually ethanol). For cases involving both cocaine and methamphetamine, the composite was a 36-year-old Caucasian man in whom was also found at least 1 other drug, usually ethanol, codeine, or morphine. Mean tissue concentrations of cocaine and benzoylecgonine were significantly higher in accidental overdoses than in homicides except for cocaine concentrations in liver, which did not differ significantly between the two groups. For methamphetamine-related deaths there was no significant difference between mean tissue concentrations in accidental overdoses and in homicides. Cocaine or methamphetamine or both were involved in approximately one third of homicides in San Diego County in 1987, and when fatal accidental overdoses were included, cocaine was involved in twice as many cases as methamphetamine.
Rats were injected intraperitoneally with 10 mg/kg of methamphetamine hydrochloride at various intervals. Administration of methamphetamine 5 injections of the dose every 4 days (the interval administration) caused an over-release of catecholamine from the adrenal gland and a significant increase of norepinephrine in the plasma. In the heart muscle, an over-release of norepinephrine and an increase of the epinephrine content occurred. In contrast, the administration of methamphetamine twice daily for 4 days (the repeated administration) induced little change in the peripheral catecholamine. A significant increase in the heart rate was observed in the interval administration group, while the repeated administration twice daily for 4 days induced little increase in the heart rate, in proportion to the changes in the plasma catecholamine - that is, the interval administration produced a reverse-tolerance in the heart, and the repeated administration led to this tolerance. Regarding the changes of rectal temperature, there was no significant difference between the groups of the single dose and the interval administration. The repeated administration produced a tolerance to the increase of rectal temperature. A reverse-tolerance or a hypersensitivity in the heart response may occur also in man after long-term methamphetamine abuse. This over-response in the heart, produced by long-term abuse, may be responsible for sudden death in abusers. Even small doses of methamphetamine might cause sudden death in abusers.
A histological study was made on 13 cases of sudden death in which methamphetamine was detected in blood or urine. Blood methamphetamine levels varied from 0 to 14.6 μg/ml. Many abrasions and contusions were demonstrated in 7 cases. Detailed histological examinations performed on 9 cases with few postmortem changes disclosed hemorrhage and congestion of the lung in the majority of cases, fatty changes of the liver in 3 cases, cloudy swelling of renal proximal tubules in 4 cases, hypertrophy and atrophy of the adrenal gland in 3 cases each and cerebral gliosis in one case. Cardiac lesions were observed in 8 cases. Of the cardiac lesions, myocardial hypertrophy and disorganization as well as fibrosis were predominant and only one case showed coronary atherosclerosis. Since the myocardial changes observed in the present study are commonly seen in hypertrophic cardiomyopathy (HCM), it is possible that profound secretion of catecholamines, particularly norepinephrine, by methamphetamine abuse is associated with the development of HCM.
The clinical presentation of intoxication with the drugs of abuse is often confusing and variable. Not only is there a large interindividual variation in sensitivity to the effects, but the illicitly purchased drugs are not pure. Identification of these patients by the emergency department staff required a high level of suspicion. Routine biochemical and hematologic determinations rarely help in identifying the specific toxin. Almost all of the illicit drugs can be identified in bodily fluids and attempts should be made to do so. The value of these specific drug assays lies in the retrospective documentation of intoxication and not in aiding in the emergency management of an acutely intoxicated patient. Finally, there are no specific 'antidotes' for these drugs of abuse. Symptomatic detailed medical care is the cornerstone to the successful management of the patient.
A case of acute left ventricular failure following an intravenous dose of amphetamine is described. The diagnosis was made by right heart catheterization. This is the first description of acute amphetamine cardiomyopathy in the medical literature.
To the Editor.
—To our knowledge, the occurrence of acute myocardial infarction in a patient with proved narcolepsy receiving long-term amphetamine treatment has not been previously reported. Our treatment of such a patient might provide useful information for other clinicians.
Report of a Case.
—A 58-year-old man was admitted to the hospital to be examined for myocardial infarction after initially being seen with severe epigastric pain. His pain was transient, but serial ECGs and enzyme levels clearly verified an acute inferior myocardial infarction. Findings from his examination and medical history were normal, except for a 15-year history of verified narcolepsy. His narcolepsy was well controlled for many years while he received 10 mg of dextroamphetamine sulfate orally four times a day. Amphetamine therapy was abruptly discontinued on hospital admission, and his initial hospital course was uneventful except for extreme physician annoyance, since the patient was always asleep during rounds
We report a case of a woman who developed acute cardiomyopathy with myocardial dysfunction and pulmonary edema immediately after intravenous amphetamine abuse. Possible causes for this severe cardiac abnormality, as well as its clinical importance, are discussed.
This article describes the cardiovascular effects and treatment of patients who have used cardiotoxic drugs. The discussion includes cocaine, methamphetamine, cyclic antidepressants, calcium channel blockers, beta-blockers, and digoxin. The authors review treatment controversies and emphasize the acute aspects of toxicity commonly seen in the emergency department.
In order to clarify the effect of methamphetamine (MA) on myocardium, histological, immunohistochemical and electron microscopic changes in the myocardium of rats were examined following daily intraperitoneal administration of MA at a dose of 1 mg per kg body weight for 4, 8, and 12 weeks before sacrifice. Normal saline (NS) was similarly injected for the same period before sacrifice to constitute a control group. Light microscopic changes found in the myocardium of the MA-treated group included atrophy, hypertrophy, patchy cellular infiltration, eosinophilic degeneration and disarray, edema myolysis, fibrosis, and the appearance of vacuoles. Ultrastructurally, nuclei and normal mitochondria had various shapes and there were dilated T tubules and sarcoplasmic reticulum, the accumulation of glycogen granules and fat droplets. Intra- and extra-cellular edema and intramyocytic vacuoles were often found. Withdrawal of MA at the twelfth week in another group of rats evidenced gradual recovery of the myocardial changes, commencing at 3 weeks after withdrawal. Optimism is therefore generated about the possibility of the affected hearts in MA-abuse patients returning towards the normal state if they give up the drug.
In an attempt to differentiate the direct effects of methamphetamine from the indirect sympathomimetic effects on the myocardium, primary culture of adult rat myocytes were established under serum-free conditions, and they were exposed to methamphetamine (1 x 10(-5) and 1 x 10(-3) M) for 1 to 24 h in the presence and absence of 1 x 10(-6) M propranolol. Cardiotoxicity was evaluated by light and ultramicroscopy, release of cytoplasmic enzymes (Lactate dehydrogenase: LDH and Creatine phosphokinase: CPK) and change in membrane permeability (Trypan blue stain). After 24 h methamphetamine treatment, light microscopy exhibited cellular granulation and swelling, myocyte hypercontraction, broken cellular membrane and cellular destruction. After the same time, electron microscopy revealed swelling and irregular mitochondria with disrupted cristaes, clump of sarcomeres with nearly complete loss of organized contractile elements, injury of intracellular membrane system and dissolution of myofibrils. These injurious features were more severe with the 1 x 10(-3) M methamphetamine. Propranolol (1 x 10(-6) M), a beta-adrenergic antagonist, failed to protect the myocytes against methamphetamine-induced cell injury. Release of LDH from methamphetamine (1 x 10(-5) and 1 x 10(-3) M)-treated myocytes increased significantly only after 24 h, while significant CPK release was observed in 1 x 10(-3) M methamphetamine-treated myocytes at 4 h. These findings suggest that methamphetamine exerts direct toxic effects on adult rat myocytes rather than indirect ones via receptors, although further experiments on more concentrations of propranolol are required.
Methamphetamine and ethanol are commonly used together. We examined the effects of intravenous methamphetamine (30 mg), oral ethanol (1 gm/kg), and the combination of methamphetamine (30 mg) and ethanol (1 gm/kg).
Eight methamphetamine and ethanol users were studied in a double-blind, double-placebo, within-subject, balanced Latin-square design. Ethanol was administered in six drinks over 30 minutes. Methamphetamine was injected 60 minutes after the first drink was begun. Cardiovascular, subjective, and neuropsychologic effects of the drug combinations were measured for 6 hours. Methamphetamine and amphetamine in plasma and urine were measured by capillary gas chromatography for 48 hours. Data were analyzed by repeated-measures ANOVA.
Compared with methamphetamine alone, the combination increased heart rate but decreased systolic blood pressure. The net cardiovascular effect was an increase in rate pressure product, an index of cardiac work and myocardial oxygen consumption. The combination diminished the subjective effects of ethanol while not affecting the subjective effects of methamphetamine. Methamphetamine pharmacokinetics were not altered by the concurrent administration of ethanol, with the exception of lowering the apparent volume of distribution at steady state for methamphetamine.
As a potent sympathomimetic drug with alpha-agonist-like effects, methamphetamine increased systolic blood pressure, with minimal change in heart rate. The concurrent administration of methamphetamine and ethanol increased cardiac work, which could produce more adverse cardiovascular effects than either drug taken alone. The increased perceived global intoxication may explain the popularity of this drug combination.
Sudden, unexpected death can occur following rupture of an artery weakened by aneurysmal dilatation or by medial dissection. In both of these diseases the arterial abnormality is exacerbated by hypertension. This arterial weakness could also be aggravated by the use of drugs with a hypertensive effect. We report seven cases of sudden death in patients abusing methamphetamine--four cases of ruptured berry aneurysms and three cases of aortic dissection with cardiac tamponade. The autopsy findings are reviewed, and various mechanisms are considered by which methamphetamine may contribute to death in such cases.
Methamphetamine has long been a drug of abuse. The smokable form of methamphetamine hydrochloride, called "ice" on the street, is twice as toxic as amphetamine and has clinical effects similar to those of cocaine. In the United States, methamphetamine use has spread eastward from Hawaii and California. Ice is a strong central nervous system stimulant. Chronic use may result in serious psychiatric, cardiovascular, metabolic and neuromuscular changes. Generally, patients presenting with methamphetamine toxicity can be treated conservatively in the emergency department. Long-term treatment usually requires drug rehabilitation and inpatient counseling.
A sample of 301 regular amphetamine users was interviewed regarding transitions between routes of administration of amphetamines. Use of amphetamines by injecting was widespread, with two-thirds (67%) of subjects having injected the drug during the preceding 6 months. Needle-sharing was common, with 41% of injectors having shared a needle in the month preceding interview. A transition to regular amphetamine injecting from other routes of administration was reported by 40% of subjects, with males being twice as likely to report such a transition. The median number of such transitions was one. The main reasons given by subjects for the transition to injecting were liking the "rush" from injecting, and seeing it as a more economical and a healthier way to use. A small proportion of subjects (9%) reported a transition away from injecting amphetamines, with a median of one such transition. The most common reason given for abandoning injecting was concern about vascular damage. Interventions to encourage safer use of amphetamines need to address the misconceptions that injecting is more economical and more healthy, and to emphasize the vascular problems associated with injecting.
A 31-year-old body-builder taking anabolic steroids, amphetamines, frumil (frusemide and amiloride), and potassium supplements collapsed with a myocardial infarction. His serum potassium was 6.7 mmol/l and he had a run of ventricular tachycardia. He was unaware of the effects of the drugs on the heart.
To examine the clinical characteristics of methamphetamine (MAP) psychosis in Japan, we evaluated 104 patients with MAP psychosis (80 men and 24 women) admitted to the closed psychiatric units of Tokyo Metropolitan Matsuzawa Hospital between 1988 and 1991. There has recently been a steep increase in the number of admissions for MAP psychosis, reflecting the growth of the epidemic of MAP abuse in Japan. Although more than half of the patients were discharged within one month, 16 patients were hospitalized for more than 3 months. Most of the patients showed paranoid psychotic state similar to schizophrenia, consistent with previous reports. Despite the abstinence from MAP and antipsychotic medication, psychotic symptoms tended to persist in some of the patients. The etiological role of MAP psychosis in the development of long-lasting psychotic state was discussed.
Methamphetamine poisoning was confirmed in eight patients admitted to intensive care 1989 through 1992 because of altered mental status and hemodynamic instability. Four patients were male and four were female, ages 20 to 34 years. Five patients were addicts and three were attempted suicides. The most common clinical cardiovascular manifestations were tachycardia and palpitations. Neurological abnormalities included agitation, hallucinations, pupillary dilatation and muscle twitching; profuse sweating was also common. All patients had rhabdomyolysis and four had remarkable elevation of creatinine kinase > 10,000 U/L. Leucocytosis was noted in seven cases. Therapy included aggressive circulatory support with Swan-Ganz monitoring, external cooling and other modalities. The three fatalities (two addicts, one suicide) presented with coma, shock, body temperature 39 degrees-42 degrees C, acute renal failure, metabolic acidosis and hyperkalemia (K 5.6-8.5 mmol/L).