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Whether a person was voluntarily or intentionally intoxicated at the time of commission of a violent offence is a common question in forensic contexts. While a person who was intoxicated may not be able to form the requisite specific intent to commit some offences, voluntary intoxication usually disentitles a person from an insanity or "mental impairment" defence. However, a person may also consume alcohol or use a substance without becoming intoxicated and the presence of alcohol, substances or metabolites of substances in a person's urine or blood is not conclusive when the question of intoxication is relevant. A jury (or a judge sitting without a jury) may require expert opinion evidence when cannabis or methamphetamine intoxication are implicated in the alleged offending., Competing Interests: None.

Background and Objectives: Methamphetamine (MA) is one of the most common addictive substances and has become the second most commonly used drug worldwide. Obsessive-compulsive disorder (OCD) has been shown to influence the effectiveness of addiction treatment, and there may be overlapping neurobiological mechanisms between OCD and addiction. The aim of this study was to investigate the prevalence and clinical correlates of OCD among MA patients., Methods: A total of 457 MA patients were recruited, and clinical and demographic data were collected. The Yale-Brown Obsessive-Compulsive Scale was utilized for OCD symptoms, and the Obsessive-Compulsive Drug Use Scale was used for MA craving., Results: The prevalence of OCD among MA patients was 7.7%. Compared to those patients without OCD, patients with OCD had a longer length of abstinence and higher OCDUS frequency of craving subscale and total scores. Multiple regression showed that longer length of abstinence and higher MA carving were independently associated with OCD in MA patients., Discussion and Conclusions: Chinese Han MA patients have a high prevalence of OCD. Some clinical parameters may be associated with OCD in MA patients., Scientific Significance: This is the first study to examine the prevalence, sociodemographic and clinical correlates of OCD in MA patients in a Chinese Han population., (© 2022 The American Academy of Addiction Psychiatry (AAAP).)

Objectives: In the United States, the number of overdose deaths related to opioids in combination with stimulants has increased; however, the Northeast has typically been less impacted by stimulant overdose. Injection drug use (IDU) results in high mortality from overdose and infectious disease and there are racial disparities observed in overdose death rates. We examined trends in stimulant and opioid IDU, including trends stratified by race, using 5 waves of cross-sectional state surveillance data., Methods: Data came from the Centers for Disease Control and Prevention's National HIV Behavioral Surveillance system Boston, Massachusetts site, which includes 5 waves of data (2005-2018) among adults in the Boston metropolitan area reporting IDU (N = 2550). Outcome measures were type of substance injected in the past 12 months (heroin, prescription opioids, "speedball," cocaine, crack, and/or methamphetamine)., Results: Participants were 70% male, 58% non-Hispanic White, and injected a mean of 3 different drugs in the past 12 months. From 2015 to 2018, there was a more than 2-fold increase in injection of methamphetamine (15% vs 38%, P < 0.001), a pattern which held across racial groups. Combination heroin and methamphetamine injection increased from 2015 (15%) to 2018 (35%, P < 0.001). Multiple drug injection (injecting >1 drug) increased significantly across years compared with single drug injection ( P = 0.03)., Conclusions: Findings suggest that increased use of methamphetamine and opioids extends to Boston. There is an urgent need for enhanced screening of methamphetamine use among those using opioids and increased access and payor coverage of efficacious treatments for stimulant and opioid use disorders (eg, contingency management and medication treatment for opioid use disorder)., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 American Society of Addiction Medicine.)

Objective: To review the literature on the neuropharmacology of synthetic cathinones., Methods: A comprehensive literature search was carried out across multiple databases (mainly PubMed, World Wide Web, and Google Scholar) using relevant keywords., Results: Cathinones exhibit a broad toxicological profile, mimicking the effects of a wide variety of 'classic drugs' such as 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine and cocaine. Even small structural changes affect their interactions with key proteins. This article reviews existing knowledge of the mechanisms of action of cathinones at the molecular level, and key findings from research on their structure-activity relationship. The cathinones are also classified according to their chemical structure and neuropharmacological profiles., Conclusions: Synthetic cathinones represent one of the most numerous and widespread groups among new psychoactive substances. Initially developed for therapeutic purposes, they quickly started to be used recreationally. With a rapidly increasing number of new agents entering the market, structure-activity relationship studies are valuable for assessing and predicting the addictive potential and toxicity of new and potential future substances. The neuropharmacological properties of synthetic cathinones are still not fully understood. A full elucidation of the role of some key proteins, including organic cation transporters, requires detailed studies., (© 2023 John Wiley & Sons Ltd.)

Methamphetamine (METH) is one of the psychostimulants most widely abused in the world. METH abuse can lead to severe neurotoxicity. The blood-brain barrier (BBB) is a natural barrier separating the central nervous system (CNS) from the peripheral blood circulation, which can limit or regulate the exchange of toxic substances, molecules, ions, etc., to maintain the homeostasis of CNS. Long-term or high dose abuse of METH can cause structural or functional abnormalities of the BBB and increase the risk of neurodegenerative diseases. In this review, we discussed the mechanisms of METH-induced BBB dysfunction, summarized the risk factors that could exacerbate METH-induced BBB dysfunction, and introduced some potential therapeutic agents. It would provide an important basis and direction for the prevention and treatment of BBB dysfunction induced by METH., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Methamphetamine use can induce psychosis resembling acute schizophrenia spectrum psychosis, making it challenging to differentiate between the two based on symptoms alone. Brain-derived neurotrophic factor (BDNF) exerts a critical role in hippocampal neural plasticity, influencing critical cognitive functions such as memory and learning. This study aimed to determine the role of serum BDNF levels in schizophrenia and methamphetamine addiction. A case-control study was conducted involving 50 patients with schizophrenia, 50 patients with methamphetamine addiction, and 50 healthy control subjects recruited from Ibn-Rushed Psychiatric Teaching Hospital in Baghdad. Cognitive impairment was assessed using the Mini-Mental State Examination (MMSE), while serum BDNF levels were measured using ELISA following standardized protocols. The findings revealed significantly lower median levels of BDNF (0.36 pg/ml) in patients with schizophrenia compared to both the control group (0.51 pg/ml) and the methamphetamine group (0.72 pg/ml). Moreover, there was a significant difference observed between the methamphetamine group and the control group. At a cut-off value of BDNF=0.37 pg/ml, the sensitivity and specificity of BDNF in differentiating between schizophrenia and methamphetamine addiction were 84% and 70%, respectively. Serum level of BDNF could be used to differentiate between schizophrenia and methamphetamine addiction when clinical distinctions are challenging to detect., Competing Interests: The authors declare no conflict of interest., (©2023 JOURNAL of MEDICINE and LIFE.)

Background: Escalating misuse of amphetamine-type stimulants, mainly methamphetamine, has led to a staggering rise in associated overdose deaths and a pressing need to understand the basis of methamphetamine use disorder (MUD). MUD is characterized by disadvantageous decision-making, and people with MUD perform below controls on the Balloon Analogue Risk Task (BART), a laboratory test of decision-making under uncertainty. The BART presents a series of choices with progressively higher stakes-greater risk of loss and greater potential monetary reward. This research aimed to clarify whether impaired behavioral updating contributes to maladaptive performance on the BART., Methods: Two groups (28 drug-abstinent participants with MUD and 16 healthy control participants) were compared on BART performance. Using a computational model, we deconstructed behavior into risk-taking and behavioral updating. A subset of participants (22 MUD, 15 healthy control) underwent [ 18 F]fallypride positron emission tomography scans to measure dopamine D2-type receptor availability (BPND) in the striatum (caudate and accumbens nuclei and putamen) and the globus pallidus., Results: Participants with MUD exhibited slower behavioral updating than the healthy controls (p = 0.0004, d=1.77). BPND in all four bilateral volumes of interest were higher in the healthy control group (ps < 0.005, ds < 2.16), and updating rate correlated positively with BPND in the caudate nucleus (p = 0.002), putamen (p = 0.002), and globus pallidus (p = 0.03)., Conclusions: The findings indicate that behavioral updating contributes to maladaptive decision-making in MUD and suggest that dysregulation of D2-type receptor signaling in the striatum and globus pallidus contributes to this behavioral deficit., Competing Interests: Conflict of interest The authors have no conflicts of interest or financial disclosures to report., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Methamphetamine is an addictive drug with various effects on the neurotransmitters in the central nervous system. Methamphetamine-induced encephalopathy in the absence of hyperammonemia presents a unique challenge in a clinical setting. Previously published cases of methamphetamine-induced encephalopathy suggested that methamphetamine-induced hepatotoxicity and subsequent hyperammonemia may be the cause of encephalopathy. However, the literature is limited on methamphetamine-induced encephalopathy without hyperammonemia., Case: This case presents a disoriented patient with methamphetamine use disorder in acute toxicity, unable to ambulate independently, and poorly responsive to verbal stimuli. The patient was found to have normal ammonia levels., Discussion: This patient's presentation and laboratory findings, namely normal ammonia levels, suggest a different pathophysiological pathway for methamphetamine-induced encephalopathy. One potential pathway is through the direct action of methamphetamine on the central nervous system through acute disruption of neurotransmitter signaling and disruption of the blood-brain barrier., Conclusion: Further research should be conducted into the prevalence and pathophysiology of methamphetamine-induced encephalopathy in the absence of hyperammonemia., Key Points: Methamphetamine-induced encephalopathy (MIE) in the absence of hyperammonemia presents a unique challenge in a clinical setting. Previously published cases of MIE suggest that methamphetamine-induced hepatotoxicity and subsequent hyperammonemia may be the cause of encephalopathy. Further research should be conducted into the prevalence and pathophysiology of MIE in the absence of hyperammonemia., (© 2023. The Author(s).)

Background: The increased use of illicit drugs continues to lead to the discovery of various unexpected pathologies., Case Presentation: This 7-month-old infant died suddenly at home. Pulmonary artery fibrinoid necrosis, diffuse fatty liver changes, and skin rash were the main histologic postmortem findings. Postmortem urine contained traces of methamphetamine. Methamphetamine was smoked by the parents., Conclusions: Fibrinoid necrosis has been described with inhaling methamphetamine and can result in fibrinoid angiitis such as in this case. Although this did not result in pulmonary hemorrhage or could be directly related to death, it does suggest that pulmonary artery fibrinoid necrosis may develop with passive inhalation of methamphetamines.

Objectives. To examine trends in methamphetamine-related mortality in the United States from 1999 to 2021 and the extent to which these deaths co-involved heroin or fentanyl. Methods. We obtained final and provisional data from the CDC WONDER (Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research) multiple causes of death database for deaths that involved methamphetamine and deaths that involved both methamphetamine and heroin or fentanyl mong US residents aged 15 to 74 years. We plotted the age-adjusted methamphetamine-related mortality rate by year and quantified the proportion of deaths with heroin or fentanyl co-involvement. Finally, we used joinpoint regression to quantify trends in the methamphetamine mortality rate and proportion of deaths with heroin or fentanyl co-involvement. Results. From 1999 to 2021, there was a 50-fold increase in the methamphetamine mortality rate, which was accompanied by an increasing proportion of deaths that co-involved heroin or fentanyl, peaking at 61.2% in 2021. Conclusions. Unprecedented increases in methamphetamine-related mortality have occurred during the last decade, and an increasing proportion of these deaths co-involved heroin or fentanyl. Public Health Implications. Stark increases in methamphetamine-related mortality and heroin or fentanyl co-involvement warrant robust harm reduction efforts, especially for people who engage in polysubstance use. ( Am J Public Health . 2023;113(4):416-419. https://doi.org/10.2105/AJPH.2022.307212).

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., (© 2022 Society for the Study of Addiction.)

Objective: Evidence reveals that γ-aminobutyric acid (GABA) receptors are involved in the development of methamphetamine (METH) dependence. The GABA receptor delta subunit gene (GABRD) might be a good candidate gene for METH dependence. In a case-control study, we investigated the association between the single nucleotide polymorphisms (SNPs) in GABRD and METH dependence in a Chinese Han population., Methods: A total of 300 METH dependent patients and 300 age and sex matched normal control subjects were recruited. Four SNPs (rs13303344, rs4481796, rs2376805, and rs2229110) in GABRD were determined with the TaqMan genotyping assay. The association of the SNPs with METH dependence was assessed., Results: Only the allele frequency of rs2376805 significantly differed between the patients and controls (P = 0.030). The G allele frequency of rs2376805 was higher in the METH dependent group than in the controls (odds ratio = 1.332, 95 % CI: 1.028-1.724). This association was found in females but not in males. In females, the frequencies of genotype and allele at rs2376805 significantly differed between the patients and controls (P = 0.025, 0.022, respectively); the rs2376805 G allele may also be a risk factor for METH dependence (odds ratio = 1.548, 95 % CI: 1.063-2.257). The haplotype ACGT frequency significantly differed between the patients and controls in total subjects (P = 0.008, odds ratio = 1.815, 95 % CI: 1.183-2.782), as well as in females (P = 0.005, odds ratio = 2.702, 95 % CI: 1.313-5.562). In females only, the METH craving score was significantly lower in patients harboring the G allele at rs2376805 than in those harboring the homozygous AA genotype (P = 0.044)., Conclusion: The preliminary results indicate that GABRD rs2376805 is associated with METH dependence, especially in females., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Methamphetamine and cannabis are two widely used substances among people living with HIV (PLWH). Whereas methamphetamine use has been found to worsen HIV-associated neurocognitive impairment, the effects of combined cannabis and methamphetamine use disorder on neurocognition in PLWH are not understood. In the present study, we aimed to determine the influence of these substance use disorders on neurocognition in PLWH and to explore if methamphetamine-cannabis effects interacted with HIV status., Method and Participants: After completing a comprehensive neurobehavioral assessment, PLWH ( n = 472) were stratified by lifetime methamphetamine (M-/M+) and cannabis (C-/C+) DSM-IV abuse/dependence disorder into four groups: M-C- ( n = 187), M-C+ ( n = 68), M+C-, ( n = 82), and M+C+ ( n = 135). Group differences in global and domain neurocognitive performances and impairment were examined using multiple linear and logistic regression, respectively, while holding constant other covariates that were associated with study groups and/or cognition. Data from participants without HIV ( n = 423) were added, and mixed-effect models were used to examine possible interactions between HIV and substance use disorders on neurocognition., Results: Compared with M+C+, M+C- performed worse on measures of executive functions, learning, memory, and working memory and were more likely to be classified as impaired in those domains. M-C- performed better than M+C+ on measures of learning and memory but worse than M-C+ on measures of executive functions, learning, memory, and working memory. Detectable plasma HIV RNA and nadir CD4 < 200 were associated with lower overall neurocognitive performance, and these effects were greater for M+C+ compared with M-C-., Conclusions: In PLWH, lifetime methamphetamine use disorder and both current and legacy markers of HIV disease severity are associated with worse neurocognitive outcomes. There was no evidence of an HIV × M+ interaction across groups, but neurocognition was most impacted by HIV among those with polysubstance use disorder (M+C+). Better performance by C+ groups is consistent with findings from preclinical studies that cannabis use may protect against methamphetamine's deleterious effects.

Objectives: Methamphetamine (METH) as a potent psychostimulant drug with a high potency of dependence rate that results in neurotoxicity has become a major drug of abuse in many parts of the world. Unfortunately, there is limited evidence regarding treatment of METH withdrawal syndrome. Therefore, we aimed to investigate whether metformin mitigate the methamphetamine (METH) withdrawal syndrome in male mice. Based on the literature, depression and anxiety are the major METH withdrawal symptoms., Methods: Here, METH (2 mg/kg) was administered to mice twice a day for 14 constitutive days to induce animal model of METH-induced withdrawal syndrome. To do this, mice in control group and those with METH withdrawal syndrome were divided into treatment (receiving metformin in 3 doses of 50, 100 and 200 mg/kg for 10 days) and non-treatment sub-groups. Following the behavioural test, the animals were sacrificed; their hippocampus was dissected to measure oxidative stress parameters and expression of cellular energy homeostasis and immune-inflammatory genes., Results: Our data revealed that metformin provoked antidepressant effects in behavioural tests through AMPK overexpression as an important mitochondrial energetic sensor and inhibition of Tlr4 overexpression in the immune system gene expression. In addition, metformin was able to improve oxidative stress biomarkers and neuronal damage in the hippocampus and restore cellular energy homeostasis and immune system gene expression., Conclusions: The data suggested that metformin can influence the hippocampus through targeting mitochondria and their performance, and consequently, neuroinflammation responses and brain metabolic changes. It is supposed to be a new therapeutic option in clinical trials of depression and anxiety following METH withdrawal treatment.

Background: Synthetic cathinones are the most used novel psychoactive substances in Taiwan because they exhibit psychoactive effects similar to those of methamphetamine, inducing acute psychosis, violence, and self-harm. However, the differences in the clinical characteristics of patients with synthetic cathinone and methamphetamine intoxication admitted to psychiatric emergency departments (EDs) remain unclear., Methods: This study recruited patients with stimulant intoxication who were admitted to a psychiatric ED from April 2019 to May 2020. Sociodemographic, lifestyle, and psychopathological data were collected through face-to-face interviews and evaluated. Immunoassay tests and liquid chromatography-quadrupole time-of-flight mass spectrometry were performed to detect substances in urine specimens. The patients were matched by sex and age (in 5-year intervals). The associations between the 2 groups and physical complications were analyzed through logistic regression., Results: Twenty-four patients with synthetic cathinone intoxication were identified and matched with 48 patients with methamphetamine intoxication. The 2 groups exhibited similar clinical severity of psychotic symptoms and high risks of violence and self-harm. Both groups were predominated by unmarried patients, unemployed patients, and habitual smokers and drinkers. However, family histories of substance use and criminal records were less prevalent among the patients with synthetic cathinone intoxication, but they had a higher rate of physical complications (odds ratio, 8.55; 95% confidence interval, 2.15-34.03), compared with patients with methamphetamine intoxication., Conclusions: Compared with patients intoxicated with methamphetamine, those intoxicated with synthetic cathinones may have similar tendencies toward psychosis, violence, and self-harm but higher risks of physical complications, which are prioritized in psychiatric EDs., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

A 33-year-old female presented with lethargy due to multidrug toxicity. At physical examination, both gluteal regions showed brown patchy scars. The atrophic scars surrounding necrotic lesions were round and brown in appearance, and gluteal mass had gradually been lost. The patient disclosed using intramuscular ketamine injections for 3.5 years along with smoking hashish, alcohol use, intranasal use of methamphetamine (sniffing), and oral use of methadone. Since recreational drug use can affect multiple organs, dermatologists should be familiar with the dermatologic features of intravenous or intramuscular injecting drug use., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Methamphetamine use is on the rise with increasing emergency department (ED) visits, behavioral health crises, and deaths associated with use and overdose. Emergency clinicians describe methamphetamine use as a significant problem with high resource utilization and violence against staff, but little is known about the patient's perspective. In this study our objective was to identify the motivations for initiation and continued methamphetamine use among people who use methamphetamine and their experiences in the ED to guide future ED-based approaches., Methods: This was a qualitative study of adults residing in the state of Washington in 2020, who used methamphetamine in the prior 30 days, met criteria for moderate- to high-risk use, reported recently receiving care in the ED, and had phone access. Twenty individuals were recruited to complete a brief survey and semi-structured interview, which was recorded and transcribed prior to being coded. Modified grounded theory guided the analysis, and the interview guide and codebook were iteratively refined. Three investigators coded the interviews until consensus was reached. Data was collected until thematic saturation., Results: Participants described a shifting line that separates the positive attributes from the negative consequences of using methamphetamine. Many initially used methamphetamine to enhance social interactions, combat boredom, and escape difficult circumstances by numbing the senses. However, continued use regularly led to isolation, ED visits for the medical and psychological sequelae of methamphetamine use, and engagement in increasingly risky behaviors. Because of their overwhelmingly frustrating experiences in the past, interviewees anticipated difficult interactions with healthcare clinicians, leading to combativeness in the ED, avoidance of the ED at all costs, and downstream medical complications. Participants desired a non-judgmental conversation and linkage to outpatient social resources and addiction treatment., Conclusion: Methamphetamine use can lead patients to seek care in the ED, where they often feel stigmatized and are provided little assistance. Emergency clinicians should acknowledge addiction as a chronic condition, address acute medical and psychiatric symptoms adequately, and provide positive connections to addiction and medical resources. Future work should incorporate the perspectives of people who use methamphetamine into ED-based programs and interventions.

Heroin and methamphetamine cause great damage to individuals and society. However, numerous withdrawal mechanisms remain unidentified. In this study, 19 heroin short-term abstinent (HSTA) patients, 20 methamphetamine short-term abstinent (MSTA) patients, and 27 healthy controls (HCs) were scanned using multimodal magnetic resonance imaging. Degraded nodes of fiber tracts were identified using automated fiber quantification. Voxel- and surface-based morphometric measurements were performed to determine the gray matter volume and cortical thickness. The MSTA and HSTA groups had abnormal diffusion metrics in a variety of bilateral corticospinal tract (CST) and left superior longitudinal tract (SLT) nodes compared with the HC group. The MSTA patients reported more severely disrupted diffusion metrics in certain nodes of the bilateral anterior thalamic radiation and left inferior fronto-occipital tract than the HSTA patients. The MSTA and HSTA groups exhibited identical cortical damage in the fusiform and superior temporal gyri, as well as in the superior frontal gyrus, posterior cerebellum, and precentral gyrus. Extensive differences in gray matter lesions were observed between the MSTA and HSTA groups. Neuroimaging mechanisms of short-term abstinence may aid in the development of rehabilitation strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Human immunodeficiency virus (HIV) continues to infect millions worldwide, negatively impacting neurobehavioral function. Further understanding of the combined effects of HIV and methamphetamine use is crucial, as methamphetamine use is prevalent in people with HIV. The HIV-associated protein Tat may contribute to cognitive dysfunction, modeled preclinically in mice using doxycycline (DOX)-inducible Tat expression (iTat). Tat may exert its effects on cognitive function via disruption of the dopamine transporter, similar to the action of methamphetamine. Additionally, Tat and methamphetamine both decrease interneuron populations, including those expressing calbindin. It is important to understand the combined effects of Tat and methamphetamine in preclinical models of HIV infection. Here, we used iTat transgenic mice and a chronic binge regimen of methamphetamine exposure to determine their combined impact on reward learning and motivation. We also measured calbindin expression in behavior-relevant brain regions. Before induction with DOX, iTat mice exhibited no differences in behavior. Chronic methamphetamine exposure before Tat induction impaired initial reward learning but did not affect motivation. Furthermore, DOX-induced Tat expression did not alter behavior, but slowed latencies to retrieve rewards. This effect of Tat, however, was not observed in methamphetamine-treated mice, indicative of a potential protective effect. Finally, Tat expression was associated with an increase in calbindin-expressing cells in the VTA, while methamphetamine exposure did not alter calbindin numbers. These findings may indicate a protective role of methamphetamine in HIV neuropathology, which in turn may help in our understanding of why people with HIV use methamphetamine at disproportionately higher rates., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: This study examined the association between methamphetamine use and psychotic symptoms in a New Zealand general population birth cohort ( n = 1265 at birth)., Methods: At age 18, 21, 25, 30, and 35, participants reported on their methamphetamine use and psychotic symptoms in the period since the previous interview. Generalized estimating equations modelled the association between methamphetamine use and psychotic symptoms (percentage reporting any symptom, and number of symptoms per participant). Confounding factors included childhood individual characteristics, family socioeconomic circumstances and family functioning. Long term effects of methamphetamine use on psychotic symptoms were assessed by comparing the incidence of psychotic symptoms at age 30-35 for those with and without a history of methamphetamine use prior to age 30., Results: After adjusting for confounding factors and time-varying covariate factors including concurrent cannabis use, methamphetamine use was associated with a modest increase in psychosis risk over five waves of data (adjusted odds ratio (OR) 1.33, 95% confidence interval (CI) 1.03-1.72 for the percentage measure; and IRR 1.24, 95% CI 1.02-1.50 for the symptom count measure). The increased risk of psychotic symptoms was concentrated among participants who had used at least weekly at any point (adjusted OR 2.85, 95% CI 1.21-6.69). Use of methamphetamine less than weekly was not associated with increased psychosis risk. We found no evidence for a persistent vulnerability to psychosis in the absence of continuing methamphetamine use., Conclusion: Methamphetamine use is associated with increased risk of psychotic symptoms in the general population. Increased risk is chiefly confined to people who ever used regularly (at least weekly), and recently.

Methamphetamine use disorder (MUD) has been associated with broad neurocognitive impairments. While the cognitive impairments of MUD have been demonstrated, the neuropathological underpinnings remain inadequately understood. To date, the published human diffusion tensor imaging (DTI) studies involving the correlation between diffusion parameters and neurocognitive function in MUD are limited. Hence, the present study aimed to examine the association between cognitive performance and white matter microstructure in patients with MUD. Forty-five patients with MUD and 43 healthy controls (HCs) completed their demographic information collection, cognitive assessments, and DTI imaging. DTI images were preprocessed to extract fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of various fiber tracts. Univariate tests were used to examine group differences in cognitive assessments and DTI metrics. Linear regression was used to examine the relationship between these two metrics. The results revealed that patients with MUD had lower subset scores of the MATRICS Consensus Cognitive Battery (MCCB), which reflects five cognitive domains: processing speed, attention, verbal learning, visual learning, problem-solving. Patients with MUD also had significantly higher AD, MD, and RD values of the left superior longitudinal fasciculus than HCs. Furthermore, the RD value of the left superior longitudinal fasciculus was a significant predictor of processing speed and problem-solving ability, as shown by the digit-symbol coding test and NAB-Mazes scores, respectively. Findings extended our understanding of white matter microstructure that is related to neurocognitive deficits in MUD and provided potential targets for the prevention and treatment of this chronic disorder., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Methamphetamine misuse, a surging cause of morbidity and mortality worldwide, identifies Methamphetamine Use Disorder (MUD) as a critical public health problem. Treatment for MUD typically is sought during early abstinence when patients are experiencing cognitive difficulties that may hamper their engagement in treatment and recovery. Cognitive difficulties, particularly those that involve executive functions, likely reflect disruptions in neural functioning involving multiple brain areas and circuits., Methods: To extend knowledge in this area, we compared individuals with MUD (MUD group, n = 30) in early abstinence (3-11 days abstinent) with a healthy control group (HC, n = 33) on brain activation and network connectivity and topology, using functional magnetic resonance imaging (fMRI) during performance on an N-back working memory task. The N-back task involves the maintenance and manipulation of information in short-term memory and engages multiple neural processes related to executive functioning. The task was administered at two working-memory difficulty loads (1-back and 2-back)., Results: Compared with the HC group, the MUD group had worse task performance but no differences in task-related brain activation. Network-based statistics analyses, however, revealed that the MUD group exhibited less functional network connectivity at both difficulty loads of the N-back task than the HC group. Additional graph theory analyses showed that path lengths were longer, and clustering was lower across these networks, which also exhibited disrupted small-world properties in the MUD group., Conclusion: These results suggest a decoupling in network dynamics that may underlie deficits in cognition during early abstinence in MUD patients., Competing Interests: Conflict of interest statement No authors have any relevant conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The opioid epidemic remains one of the most pressing public health crises facing the United States. Fentanyl and related synthetic opioid agonists have largely driven the rising rates of associated overdose deaths, in part, because of their surreptitious use as substitutes for other opioids and as adulterants in psychostimulants. Deaths involving opioids typically result from lethal respiratory depression, and it is currently unknown how co-use of psychostimulants with opioids affects respiratory toxicity. Considering psychostimulant overdoses have increased over 3-fold since 2013, and half of those co-involved opioids, this is a cardinal question., Methods: Naloxone, d-amphetamine (AMPH), and (±)-methamphetamine (METH) were evaluated for their effects on basal and fentanyl-depressed respiration. Minute volume (MVb) was measured in awake, freely moving mice via whole-body plethysmography to quantify fentanyl-induced respiratory depression and its modulation by dose ranges of each test drug., Results: Naloxone immediately reversed respiratory depression induced by fentanyl only at the highest dose tested (10 mg/kg). Both AMPH and METH exhibited bidirectional effects on MVb under basal conditions, producing significant (p ≤ 0.05) depressions then elevations of respiration as dose increased. Under depressed conditions the bidirectional effects of AMPH and METH on respiration were exaggerated, exacerbating and then reversing fentanyl-induced depression as dose increased., Conclusions: These results indicate that co-use of amphetamines with fentanyl may worsen respiratory depression, but conversely, monoaminergic components of the amphetamines may possibly be exploited to mitigate fentanyl overdose., Competing Interests: Conflict of interest No conflict declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Methamphetamine is the second leading cause of overdose death in America and a leading cause of emergency department (ED) visits. Methamphetamine-induced psychosis is a dangerous and difficult-to-treat consequence of methamphetamine use. We describe the pilot implementation and outcomes of a multimodal treatment intervention for ED patients with methamphetamine psychosis, Beginning Early and Assertive Treatment for Methamphetamine Psychosis (BEAT Meth)., Methods: BEAT Meth was implemented in an urban safety net health system. The protocol includes early identification and treatment of methamphetamine psychosis, a protocolized hospitalization, and support for transitioning patients to specialty addiction treatment. Patients receiving BEAT Meth were compared with ED patients with methamphetamine psychosis who were discharged. Implementation fidelity was measured to assess feasibility., Results: BEAT Meth patients were nearly 3 times more likely to attend an outpatient specialty addiction appointment in the 30 days after discharge than comparison patients (32% vs 11%, P < 0.01). Subsequent ED utilization was common among all patients, and there was no significant difference in 30-day ED return rates between BEAT Meth and comparison patients (28% vs 37%, P = 0.10). Exploratory analyses suggested that increased attendance at outpatient treatment reduced ED utilization., Conclusions: BEAT Meth is an intervention framework to support identification, management, and treatment engagement of ED patients with methamphetamine psychosis. Treatment strategies like BEAT Meth are necessary to manage the unique challenges of methamphetamine addiction. These findings will guide clinical care, program development, and research., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 American Society of Addiction Medicine.)

The use of methamphetamines is growing worldwide with cardiovascular disease as the leading cause of mortality and morbidity. Long-term use of methamphetamines is associated with malignant hypertension, myocardial ischemia, pulmonary hypertension, and methamphetamines-associated cardiomyopathy. These effects are noted to be dose-dependent and potentially reversible with discontinuation of methamphetamines in the early stages when there is limited or no myocardial fibrosis. This review aims to (1) summarize the available data from epidemiologic studies, (2) describe pathophysiological mechanisms and clinical presentation, (3) Management of methamphetamines induced cardiomyopathy and potential complications associated with it, and (4) Strategies to reduce methamphetamines abuse and related hospitalization., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: There is a lack of studies on methamphetamine (MA) exposure and morbidity in children beyond the perinatal period., Objectives: We compared morbidity in children (0-3 years) with prenatal MA exposure to opioid-exposed and to non-exposed children., Methods: We used data from a Czech nationwide, registry-based cohort study (2000-2014). Children, who reached 3 years of age, of mothers hospitalized with (i) MA use disorder during pregnancy (MA; n = 194), (ii) opioid use disorder during pregnancy (opioids; n = 166), and (iii) general population (GP; n = 1,294,349) with no recorded history of substance use disorder (SUD). Information on inpatient contacts, length of stay, and diagnoses (International Statistical Classification of Diseases and Related Health Problems 10th Revision [ICD-10]) were assessed. Crude and adjusted odds ratios (aOR), 95% confidence interval (CI) for the risk of hospitalization, and for getting diagnosis from the ICD-10 diagnosis chapters were calculated using binary logistic regression. A stratified analysis on hospitalizations with SUD of mothers was performed., Results: No significant differences were found in the measures of hospitalization between the MA and opioid groups. Children prenatally exposed to MA and opioids had higher numbers of hospitalizations and diagnoses and longer stays in hospital than children in the GP. Increased risks of certain infectious and parasitic diseases were found in both MA (aOR = 1.6; CI: 1.1-2.3) and opioid (aOR = 1.9; 1.3-2.8) groups as compared to the GP group. The most pronounced difference in stratified analysis on maternal hospitalizations related to SUD after birth was observed for injury, poisoning, and certain other consequences of external causes in the strata of the MA group who had hospitalized mothers (aOR 6.3, 1.6-24.6) compared to the strata without maternal hospitalizations (aOR 1.4, 0.9-2.3)., Conclusion: This study suggests that children born to mothers using MA during pregnancy have similar morbidity during the first 3 years of life but higher than the GP. The excess of risk was primarily due to infections and injuries in the MA group., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Methamphetamine-associated cardiomyopathy (MaCM) is an increasingly recognised serious complication from methamphetamine (MA) use. It is characterised as the development of otherwise unexplained heart failure in the context of MA use. MaCM predominantly affects a young and vulnerable population with high morbidity and mortality. It is the second leading cause of mortality in patients with MA use disorder (MUD). Our understanding of MaCM pathogenesis is based on observational cohorts and autopsy studies. Currently, the treatment of MaCM is predicated on abstinence. Medical therapies offer some benefit to a minority of patients; however, without abstinence, medical therapies are often ineffective. Abstinence is difficult for most patients to achieve; all clinicians require an understanding of MaCM and how to educate patients on the risks of ongoing use. Where available, referral to addiction medicine specialists to assist with treatment of MUD is recommended. This review aims to: (i) explain the proposed pathologic mechanisms of MaCM; (ii) summarise recent recommendations of the screening and treatment of MaCM; and (iii) highlight the role of addiction medicine in the management of patient with MaCM., (© 2023 Royal Australasian College of Physicians.)

Background : Drug-related deaths in the US continue to increase. Sentinel surveillance of high-risk populations can provide early warning for shifts in trends. Nightclub/festival attendees have high levels of drug use, so we explored whether use among this population can serve as a potential bellwether or indicator for use-related mortality in the general population. Methods : Trends in past-year cocaine and methamphetamine use were estimated from nightclub/festival attendees in New York City (NYC) and among NY residents, and trends were estimated for related death rates in NYC (2014/15-2019/20). Using national data from England and Wales (2010-2019), trends in past-year cocaine and ecstasy use (among the full population and among nightclub attendees) and related deaths were also estimated. Results : In NY/NYC, cocaine use remained stable in the general population, but use among nightclub/festival attendees and cocaine-related deaths doubled. Methamphetamine use among nightclub/festival attendees and death rates also more than doubled while use among the general population remained stable. In UK countries, increases in cocaine and ecstasy use were larger for infrequent/frequent nightclub attendees than in the general population, with 3.6- and 8-fold increases in related deaths, respectively. In UK countries, the association between nightclub attendance and death rates increased in a dose-response-like manner with larger associations detected when death rates were lagged by one year. Conclusions : Patterns of use among nightclub/festival attendees, more so than patterns in the general population, were similar to patterns of drug-related deaths. Use among this subpopulation could possibly serve as a bellwether for use-related outcomes. Continued surveillance is recommended.

The cognitive processing of drug-related cues and the subsequent dysregulation of behaviour play a central role in the pathophysiology of substance use disorders. Prior studies are limited by small sample sizes and a lack of immersion in stimulus presentation. In the present study, we recruited patients with methamphetamine use disorder (MUD; N = 1099) from four compulsory isolated detoxification centres and healthy control participants (N = 305). With a 12-min-long virtual reality (VR) protocol stimulus, we discovered that patients showed a decrease in electroencephalogram (EEG) power across alpha to gamma bands in anterior scalp regions under methamphetamine-related VR stimuli (e.g. a glass pipe and medical tubing) compared with the control stimuli (e.g. balls and cubes). Analysis of variance (ANOVA) showed that the interaction effects of stimuli type and group were significant in five EEG bands. Using generalised linear models, we classified the stimuli type (i.e. drug-related vs. drug-unrelated cues) in MUD patients with an f1 score of 90% on an out-of-sample testing set. The decreases of EEG between drug-related cues and drug-unrelated cues in delta, theta and alpha frequency bands are more frequently seen in patients than in healthy controls, perhaps reflecting general arousal and attenuated impulsive control. Our results suggest that EEG responses elicited by long-duration methamphetamine-related VR cues showed a specific signature, which may have future clinical implications., (© 2022 Society for the Study of Addiction.)

Cross-border activities are possibly associated with the use of amphetamine-type stimulants (ATS), this study was to explore poly-substance of ATS use and influencing factors among ATS use populations in southwest China. A cross-sectional study was conducted by response driven and continuous samplings from January to July 2021. Descriptive, univariate and logistic regression were carried out. ATS users accounted for 95.6% of the target population, of whom one-third had cross-border experiences with 4.1% of the cross-border purchase of drugs. ATS users were mainly over 31 years old (53.9%), male (98.7%), minority (79.1%), and unmarried (72.7%). Cross-border users consumed more ketamine (8%) and methamphetamine (40%) ( P  < .05). After adjusting for socioeconomic-demographic factors, cross-border activity [OR: 0.336 (0.141, 0.799)], occupation [OR: 0.273 (0.080, 0.929)], injecting drug behavior [OR: 6.239 (1. 087, 35.811)], frequency [OR: 0.251 (0.073, 0.859)], and ATS use location [OR: 2.915 (1.040, 8.168)] were possible factors influencing ATS use patterns ( P  < .05). Cross-border activity may be associated with polydrug use, especially predominantly methamphetamine use, among ATS users along the Southwest border. It implied that the focus of drug prevention and control in border areas should be on cross-border populations., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: The opioid epidemic has evolved into a combined stimulant epidemic, with escalating stimulant and fentanyl-related overdose deaths. Primary care providers are on the frontlines grappling with patients' methamphetamine use. Although effective models exist for treating opioid use disorder in primary care, little is known about current clinical practices for methamphetamine use., Methods: Six semistructured group interviews were conducted with 38 primary care providers. Interviews focused on provider perceptions of patients with methamphetamine use problems and their care. Data were analyzed using inductive and thematic analysis and summarized along the following dimensions: (1) problem identification, (2) clinical management, (3) barriers and facilitators to care, and (4) perceived needs to improve services., Results: Primary care providers varied in their approach to identifying and treating patient methamphetamine use. Unlike opioid use disorders, providers reported lacking standardized screening measures and evidence-based treatments, particularly medications, to address methamphetamine use. They seek more standardized screening tools, Food and Drug Administration-approved medications, reliable connections to addiction medicine specialists, and more training. Interest in novel behavioral health interventions suitable for primary care settings was also noteworthy., Conclusions: The findings from this qualitative analysis revealed that primary care providers are using a wide range of tools to screen and treat methamphetamine use, but with little perceived effectiveness. Primary care faces multiple challenges in effectively addressing methamphetamine use among patients singularly or comorbid with opioid use disorders, including the lack of Food and Drug Administration-approved medications, limited patient retention, referral opportunities, funding, and training for methamphetamine use. Focusing on patients' medical issues using a harm reduction, motivational interviewing approach, and linkage with addiction medicine specialists may be the most reasonable options to support primary care in compassionately and effectively managing patients who use methamphetamines., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Addiction Medicine.)

Issues: Cessation of methamphetamine use may result in a characteristic withdrawal syndrome, no medication has been approved for this indication. This systematic review aims to assess the efficacy of pharmacotherapy for methamphetamine withdrawal, the first comprehensive meta-analysis since 2008., Approach: MEDLINE (1966-2020), CINAHL (1982-2020), PsychINFO (1806-2020) and EMBASE (1947-2020) were systematically searched. Studies were included if they were randomised controlled trials (RCT) investigating pharmacological treatments for methamphetamine withdrawal, reviewing outcomes of treatment discontinuation, mental health outcomes, withdrawal symptoms (including craving) and patient safety. The relative risk (RR) and weighted mean difference (MD) were used to meta-analyse dichotomous and continuous data respectively, with 95% confidence intervals. Risk of bias and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessments were conducted., Key Findings: Nine RCTs of six medications (n = 242 participants) met inclusion criteria, however, only six trials of four medications (n = 186) could be meta-analysed. Mean sample size across studies was 27 participants, and 88% of participants were male. The quality of evidence in this review varies from low to very low on GRADE assessments. Amineptine may reduce discontinuation rates (RR 0.22, 95% confidence interval [CI] 0.07, 0.72, p = 0.01), and improve global state (MD -0.49, 95% CI -0.80, -0.17), compared with placebo, however, this medication is no longer approved. No other medications improved any domain when compared with placebo. Due to lack of reporting safety profiles could not be established., Conclusions: There is insufficient evidence to indicate any medication is effective for the treatment of methamphetamine withdrawal. The poor quality of the evidence indicates a need for better powered, high-quality trials., (© 2022 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

This review focuses on the effects and mechanisms of action of amphetamine-type stimulants (ATS) and their adverse effects on the cardiovascular, nervous, and immune systems. ATS include amphetamine (AMPH), methamphetamine (METH, "crystalmeth," or "ice"), methylenedioxymethamphetamine (MDMA, "ecstasy," or "Molly"), MDMA derivatives (e.g., methylenedioxyamphetamine [MDA] and methylenedioxy-N-ethylamphetamine [MDEA]), khat, and synthetic cathinones. The first section of this paper presents an overview of the historical aspects of ATS use, their initial clinical use, and regulations. The second part reviews the acute and chronic impact and the most salient clinical effects of ATS on the central nervous and cardiovascular systems, skin, and mouth. The chemical structure, pharmacokinetics, and classic and non-canonical pharmacological actions are covered in the third section, briefly explaining the mechanisms involved. In addition, the interactions of ATS with the central and peripheral immune systems are reviewed. The last section presents data about the syndemic of ATS and opioid use in the North American region, focusing on the increasing adulteration of METH with fentanyl., (Copyright: © 2023 Permanyer.)

Background and Objectives: Antisocial personality disorder (ASPD) is very common among methamphetamine (MA) patients, but very few studies have been conducted in China. This study aimed to investigate the prevalence and clinical correlates of ASPD among Chinese MA patients., Methods: We recruited 627 MA patients and collected demographic and MA use data through one-on-one semi-structured interviews. ASPD was measured by the Mini International Neuropsychiatric Interview (M.I.N.I.). The Desires for Drug Questionnaire (DDQ) and visual analog scale (VAS) were used to assess drug cravings., Results: The prevalence rate of ASPD among MA patients was 27.59% (173/627). Patients with ASPD had greater age at the first onset, duration of MA use, length of abstinence, VAS, DDQ desire and intention, negative reinforcement, and total DDQ scores than patients without ASPD. Stepwise binary logistic regression analysis revealed that age, age at the first onset, length of abstinence, and DDQ-negative reinforcement were independently associated with ASPD in MA patients., Discussion and Conclusions: Our findings suggest that the prevalence of ASPD is high among Chinese MA patients. Furthermore, some demographic and clinical variables are associated with ASPD in MA patients., Scientific Significance: We focused our study on the clinical profile of ASPD and the reasons for its high prevalence in Chinese methamphetamine patients. We identified several demographic and clinical variables as correlates of the occurrence of ASPD in methamphetamine patients, which provides evidence for ASPD comorbidity in methamphetamine patients., (© 2022 American Academy of Addiction Psychiatry.)

Background and Objectives: The aim of this study was to investigate the prevalence of posttraumatic stress disorder (PTSD) and clinical correlates in Chinese methamphetamine patients., Methods: We analyzed 481 Chinese methamphetamine patients., Results: The prevalence of PTSD among Chinese methamphetamine patients was 7.90% (38/481), which was higher than in western countries. Binary logistic regression showed that age, smoking, abstinence time, age of onset, and DDQ control dimensions were associated with PTSD., Conclusions and Scientific Significance: Our results indicated that some demographic and clinical variables were associated with PTSD in Chinese methamphetamine patients, which provided evidence for PTSD comorbidity with methamphetamine., (© 2022 The American Academy of Addiction Psychiatry (AAAP).)

Background: Over the past decade, the number of individuals requiring medical care for amphetamine-related psychosis has increased., Objective: This study aims to examine the psychological characteristics of amphetamine psychosis in drug-addicted patients depending on the length of drug exposure and compared to patients diagnosed with paranoid schizophrenia., Methods: The study was carried out in psychiatric clinic No. 1 in Kyiv (Ukraine) in 2019, involving 107 patients. Of all the participants, 50 were included in Group 1 (methamphetamine psychosis) and 57 - in Group 2 (paranoid schizophrenia). All patients were treated with medication to relieve exacerbating symptoms. They underwent extensive testing to determine the impairment severity of cognitive function, attention, and task performance during remission., Results: In Group 1, the timing of onset for paranoid symptoms depends on the length of amphetamine exposure (Spearman correlation coefficient = 0.89). The efficacy and dynamics of drug treatment in Group 2 were similar to patients in Group 1. However, the effect of reduction in Group 2 was achieved only in 4 months. Delusions, emotional disturbances, hallucinations in patients of Group 1 occurred 2.3 times more frequently than in Group 2 (p ≤ 0.05). The patients of Group 1 are characterized by the presence of disorders related to the affective and behavioral components., Conclusion: All reported exacerbations are related to amphetamine use. Patients in Group 1 learned a smaller number of words compared to those in Group 2. Besides, a large number of errors and difficulties with shifting focus were recorded., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: Cognitive dysfunction and posttraumatic stress disorder (PTSD) are common in methamphetamine patients. However, few studies have investigated the cognitive performance of methamphetamine patients with PTSD. The purpose of this study was to investigate the impact of comorbid PTSD on cognitive function in Chinese male methamphetamine patients., Methods: We analyzed 464 methamphetamine patients and 156 healthy volunteers. The PTSD Screening Scale (PCL-5) was used to assess PTSD and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function., Results: Compared with healthy controls, methamphetamine patients had more cognitive dysfunction in immediate memory, visuospatial/constructional, language, attention and delayed memory. Moreover, methamphetamine patients with PTSD had less cognitive dysfunction in immediate memory, attention, and delayed memory than methamphetamine patients without PTSD. Further stepwise regression analysis showed that PTSD alterations in arousal and reactivity cluster were risk predictors for language, and PTSD negative alteration in cognition and mood cluster were risk predictors for delayed memory., Conclusions: Our results indicate that methamphetamine patients without PTSD have poorer cognitive dysfunction than those with PTSD. Some demographic and PTSD symptom clusters are protective or risk factors for cognitive dysfunction in methamphetamine patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Inc.)

Background: The comorbidity between substance use disorder and major depressive disorder is a typical dual diagnosis in the field of substance addiction. However, the prevalence and correlates of depression in methamphetamine addicts and whether it is associated with drug craving and alexithymia have been rarely reported in the Chinese population., Methods: We recruited 585 methamphetamine-dependent males from a drug rehabilitation center in China and 203 healthy controls. Demographic and drug use data were collected. Depression was assessed using the Mini International Neuropsychiatric Interview (M.I.N·I.). Methamphetamine cravings and alexithymia were assessed using the Desire for Drugs Questionnaire (DDQ) and the Toronto Alexithymia Scale (TAS)., Results: The prevalence rate of depression in methamphetamine-dependent men was 16.58 % (97/585). The scores of DDQ desire and intention, DDQ negative reinforcement, total DDQ, difficulty identifying feelings (DIF), difficulty describing feelings (DDF), and total TAS score of depressed patients were higher than those of non-depressed patients. However, only DDQ negative reinforcement score, DIF, DDF, and total TAS score remained significant after Bonferroni correction. Additionally, logistic regression analysis found that age, DIF score, and DDQ negative reinforcement score were significant factors contributing to depression in methamphetamine-dependent men., Conclusion: Our findings suggest that the prevalence of depression is significantly higher in methamphetamine-dependent men than in the healthy Chinese population. Furthermore, age, components of alexithymia and drug craving are risk factors for depression in methamphetamine addicts., Competing Interests: Conflict of Interest None., (Copyright © 2022. Published by Elsevier B.V.)

Aims: Atrial fibrillation (AF) is now regarded as a preventable disease, requiring a search for modifiable risk factors. With legalization of cannabis and more lenient laws regarding the use of other illicit substances, investigation into the potential effects of methamphetamine, cocaine, opiate, and cannabis exposure on incident AF is needed., Methods and Results: Using Office of Statewide Health Planning and Development databases, a longitudinal analysis was performed of adult Californians ≥18 years of age who received care in an emergency department, outpatient surgery facility, or hospital from 1 January 2005 to 31 December 2015. Associations between healthcare coding for the use of each substance and a new AF diagnosis were assessed. Among 23,561,884 patients, 98 271 used methamphetamine, 48 701 used cocaine, 10 032 used opiates, and 132 834 used cannabis. Of the total population, 998 747 patients (4.2%) developed incident AF during the study period. After adjusting for potential confounders and mediators, use of methamphetamines, cocaine, opiates, and cannabis was each associated with increased incidence of AF: hazard ratios 1.86 [95% confidence interval (CI) 1.81-1.92], 1.61 (95% CI 1.55-1.68), 1.74 (95% CI 1.62-1.87), and 1.35 (95% CI 1.30-1.40), respectively. Negative control analyses in the same cohort failed to reveal similarly consistent positive relationships., Conclusion: Methamphetamine, cocaine, opiate, and cannabis uses were each associated with increased risk of developing incident AF. Efforts to mitigate the use of these substances may represent a novel approach to AF prevention., Competing Interests: Conflict of interest: T.A.D. reports consulting for Adagio Medical and Farapulse. G.M.M. reports grants from the NIH (NHLBI, NIBIB), PCORI, California TRDRP, and Baylis Medical; consulting for Johnson and Johnson and InCarda; and stock in InCarda. All other authors declare that there are no conflicts of interest to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: This review aims to summarise the role of endocannabinoid system (ECS), incluing cannabinoid receptors and their endogenous lipid ligands in the modulation of methamphetamine (METH)/morphine-induced memory impairments., Methods: Here, we utilized the results from researches which have investigated regulatory role of ECS (including cannabinoid receptor agonists and antagonists) on METH/morphine-induced memory impairments., Results: Among the neurotransmitters, glutamate and dopamine seem to play a critical role in association with the ECS to heal the drug-induced memory damages. Also, the amygdala, hippocampus, and prefrontal cortex are three important brain regions that participate in both drug addiction and memory task processes, and endocannabinoid neurotransmission have been investigated., Conclusion: ECS can be regarded as a treatment for the side effects of METH and morphine, and their memory-impairing effects.

Methamphetamine (METH) is a psychostimulant that is abused throughout the world. METH is a highly addictive drug commonly used by persons living with HIV, and its use can result in cognitive impairment and memory deficits. METH and human immunodeficiency virus-1 transactivator of transcription (HIV-1Tat) have toxic and synergistic effects on the nervous system; however, the mechanism of their synergistic effects has not been clarified. We used BV2 cells, primary microglia, Nrf2-KO C57BL/6J mice, and autopsied brain tissues of METH-abusing, HIV infection, and METH-abusing individuals comorbid with HIV to explore the regulatory role of Nrf2/NQO1/HO-1 signal pathway on microglia autophagy. Our results showed that microglia were significantly activated by METH and HIV-1Tat protein. METH and HIV-1Tat protein combination significantly increase the autophagy-related proteins (LC3-II, Beclin-1, ATG5, and ATG7) expression in microglia and striatum of C57BL/6J mice. After silencing or knocking out the Nrf2 gene, the expression levels of autophagy-related proteins were significantly increased. In human brain tissue, microglia were activated, Nrf2, LC3-II, and Beclin-1 expression levels were raised, and the p62 expression level was decreased. Our results suggested that METH and HIV or HIV-1Tat synergistically affect autophagy. And the Nrf2 pathway plays a vital role in regulating the synergistic induction of microglial autophagy by METH and HIV-1Tat protein. This study may provide a theoretical basis and new ideas for effective targets for pharmacological intervention in HIV-infected patients with drug abuse., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. A:BV2 cells were treated with 0–0.8 mM METH for 24 h; B:BV2 cells were treated with 0.1 mM METH for 0,0.5,1,3,6,12 and 24 h, respectively. C: mPMs were treated with 0–0.8 mM METH for 24 h; D: mPMs were treated with 0.1 mM METH for 0, 0.5,1,3,6,12 and 24 h, respectively. The protein expression of LC3-II, Beclin-1, ATG5, and ATG7 was determined with Western blot and quantitative analyses. β-Actin was used as a loading control. Data were expressed as LC3-II/β- Actin, Beclin-1/β-Actin, ATG5/β-Actin, and ATG7/β-Actin and presented as mean ± SD from three independent experiments. (*P &lt; 0.05, **P &lt; 0.01, ***P &lt; 0.001 vs control group). A:BV2 cells were co-treated with 25,50,100 nM HIV-1Tat protein and 0.1 mM METH for 12 h.B:BV2 cells were treated with 0.1 mM METH and 50 nM HIV-1Tat protein for 12 h. C: mPMs were co-treated with 50,100 nM HIV-1Tat protein and 0.1 mM METH for 12 h.D:mPMs were treated with 0.1 mM METH and 50 nM HIV-1Tat protein for 12 h.A, C: The protein expression of LC3-II and Beclin-1 was determined with Western blot and quantitative analyses.β-Actin was used as a loading control. Data were expressed as LC3-II/β-Actin and Beclin-1/β-Actin and presented as mean ± SD from three independent experiments. B: The expression of LC3-II was analyzed by IF, Merged images of BV2 cells stained with DAPI, anti-LC3-II antibodies (red)(a: Control; b:METH; c: HIV-1Tat'd: METH + HIV-1Tat).D: The expression of LC3-II was analyzed by IF, Merged images of mPMs stained with DAPI, anti-IBA1 antibodies (red),anti-LC3-II antibodies (green)(a:Control; b:METH; c:HIV-1Tat; d:METH + HIV-1Tat).Scale bar as indicated. (*P &lt; 0.05, **P &lt; 0.01, ***P &lt; 0.001 vs control; (#)P &lt; 0.05, (##)P &lt; 0.01, (###)P &lt; 0.001vs METH group). A:BV2 cells were treated with 0–0.8 mM METH for 24 h; B:BV2 cells were treated with 0.1 mM METH for 0, 0.5,1,3,6,12 and 24 h,respectively. C: mPMs were treated with 0–0.8 mM METH for 24 h; D:mPMs were treated with 0.1 mM METH for 0, 0.5,1,3,6,12 and 24h, respectively. A-H: The protein expression of Nucleus Nrf2 (N-Nrf2) and Total Nrf2 (T-Nrf2) was determined with Western blot and quantitative analyses.β-Actin, and LaminB1 was used as a loading control. Data were expressed as N-Nrf2/LaminB1 and T-Nrf2/β-Actin and presented as mean ± SD from three independent experiments. (*P &lt; 0.05, **P &lt; 0.01, ***P &lt; 0.001 vs control) BV2 cells and mPMs were treated with or without 1.25 μM SFN (Nrf2 agonist) for 1 h before 0.1 mM METH and 50 nM HIV-1Tat protein for 12 h, respectively. A, B, D, E: The protein expression of LC3-II, Beclin-1, ATG5 and ATG7, N-Nrf2, and T-Nrf2 was determined with Western blot and quantitative analyses.β-Actin and LaminB1 was used as a loading control. Data were expressed as N-Nrf2/LaminB1, T-Nrf2/β-Actin, LC3-II/β-Actin, Beclin-1/β-Actin, ATG5/β-Actin and ATG7/β-Actin, and presented as mean ± SD from three independent experiments. C, F: The expression of LC3-II was analyzed by IF.Merged images of BV2 cells stained with DAPI, anti-LC3-II antibodies (red),anti–HO–1 antibodies (green)(a:control; b:SFN; c:METH; d:HIV-1Tat; e:METH + HIV-1Tat; f:SFN + METH + HIV-1Tat).F:Merged images of mPMs stained with DAPI, anti-LC3-II antibodies (green),anti-IBA1antibodies (red)(a:control; b:SFN; c:METH; d:HIV-1Tat; e:METH + HIV-1Tat; f:SFN + METH + HIV-1Tat).Scale bar as indicated.(*P &lt; 0.05, **P &lt; 0.01, ***P &lt; 0.001 vs control; (#)P &lt; 0.05,(##)P &lt; 0.01,(###)P &lt; 0.001 vs METH,(&)p &lt; 0.05,(&&)p &lt; 0.01,(&&&)p &lt; 0.001 vs HIV-1 Tat protein;($)p &lt; 0.05,($$)p &lt; 0.01, ($$$)p &lt; 0.001 vs. METH + HIV-1 Tat protein). mPMs and BV2 cells were transfected with siRNA-NC, siRNA-Nrf2-769, siRNA- Nrf2-481 and siRNA-Nrf2-109, respectively. The transfection efficiency was analyzed by Western Blot (A, D) and Q-PCR (B, E). C, F: BV2 cells and mPMs were treated with 0.1 mM METH and 50 nM HIV-1Tat protein for 12 h after siRNA-Nrf2-109.The protein expression of LC3-II, Beclin-1, ATG5, and ATG7 was determined with Western blot and quantitative analyses.β-Actin and LaminB1 were used as a loading control. Data were expressed as N-Nrf2/LaminB1, T-Nrf2/β-Actin, LC3-II/β-Actin, Beclin-1/β-Actin, ATG5/β-Actin and ATG7/β-Actin, and presented as mean ± SD from three independent experiments. G,H:The expression of LC3-II were analyzed by IF.G:Merged images of BV2 cells stained with DAPI, anti-LC3-II antibodies (red)(a:Control; b:METH; c:HIV-1Tat; d:METH + HIV-1Tat).H:Merged images of mPMs stained with DAPI, anti-LC3-II antibodies (green), anti-IBA1antibodies (red) (a:Control; b:METH; c:HIV-1Tat; d:METH + HIV-1Tat).Scale bar as indicated.(*P &lt; 0.05, **P &lt; 0.01,***P &lt; 0.001 vs control; (#)P &lt; 0.05, (##)P &lt; 0.01, (###)P &lt; 0.001 vs METH, (&&)p &lt; 0.01, (&&&)p &lt; 0.001 vs HIV-1 Tat protein). A: The protocol for establishing METH and HIV-1 Tat protein treated WT- and Nrf2-KO C57BL/6J mice. The brain stereotaxic striatum was injected with HIV-1Tat protein once; METH was injected intraperitoneally for 5 days. And the WT mice were treated with SFN for 1 h before METH injection. Behavioral analysis of the open-field test was performed before, on the day, and after administration of HIV-Tat protein and METH. Then the striatum was extracted for the detection of Nrf2 and autophagy-related proteins by Western Blot. B, C: The protein expression of N-Nrf2, T-Nrf2, HO-1, NQ01, LC3-II, Beclin-1, ATG5, and ATG7 were determined by Western blot and quantitative analyses in WT-mice.β-Actin and LaminB1 were used as a loading control. Data were expressed as N-Nrf2/LaminB1, T-Nrf2/β-Actin, LC3-II/β-Actin, Beclin-1/β- Actin, ATG5/β-Actin, and ATG7/β-Actin, and presented as mean ± SD from three independent experiments. The protein expression of LC3-II, Beclin-1, ATG5, and ATG7 were determined by Western blot and quantitative analyses in Nrf2-KO mice (D) and control and METH + HIV-1Tat protein group of WT and Nrf2-KO mice (E). F: The protein expression of p62 was determined by Western blot and quantitative analyses in WT- and Nrf2-KO mice.β-Actin was used as a loading control. Data were expressed as LC3-II/β-Actin, Beclin-1/β-Actin, ATG5/β-Actin, ATG7/β-Actin, and p62/β-Actin, and presented as mean ± SD from three independent experiments.The microglial activation and microglial expression of LC3 were detected by IHC and IF in striatum of WT-mice (G,I)(a:Control; b:METH; c:HIV-1Tat; d:METH + HIV-1Tat) and Nrf2-KO mice (H,J) (a:Control; b:METH; c:HIV-1Tat; d:METH + HIV-1Tat.(*P &lt; 0.05, **P &lt; 0.01, ***P &lt; 0.001 vs control; (#)P &lt; 0.05, (##)P &lt; 0.01, (###)P &lt; 0.001 vs METH; (&)p &lt; 0.05, (&&)p &lt; 0.01,(&&&)p &lt; 0.001vs HIV-1 Tat protein;($)p &lt; 0.05,($$$)p &lt; 0.001 vs METH + HIV-1Tat protein). A, B: The expression of IBA1 was detected by IF and IHC.A: Merged images of striatum stained with DAPI, anti-IBA1 antibodies (red). C: The expression of T-Nrf2 was observed by IHC.D: The expression of Nrf2 and IBA1 were analyzed by immunofluorescence, Merged images of striatum stained with DAPI, anti-IBA1antibodies (red),anti-Nrf2 antibodies (green).D: The expression of T-Nrf2, LC3-II, Beclin-1, and p62 were determined by Western blot, and quantitative analyses.β-Actin was used as a loading control. Data were expressed as T-Nrf2/β-Actin, LC3-II/β- Actin,Beclin-1/β-Actin,and p62/β-Actin,and presented as mean ± SD from three independent experiments.(**P &lt; 0.01,***P &lt; 0.001 vs control;(#)P &lt; 0.05 vs METH;(&)p &lt; 0.05 vs HIV). METH and HIV-1 Tat protein synergistically induced autophagy. Activated Nrf2 reduced the level of autophagy; siRNA Nrf2 or knocked out Nrf2 gene enhanced the level of oxidative stress and autophagy., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This clinical report describes the prosthetic restoration of a failing dentition subsequent to methamphetamine abuse. The treatment involved the use of endosteal dental implants and milled cobalt-chromium, screw-retained, implant-supported fixed dental prostheses. At the 1-year follow-up, the prosthetic rehabilitation had markedly improved the patients' health, esthetics, and function., (Copyright © 2021 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Background: Methamphetamine-associated cardiomyopathy (MA-CMP) is an increasingly recognised aetiology of cardiomyopathy. Cardiovascular magnetic resonance (CMR) is a specialised cardiac imaging modality commonly used in assessment of cardiomyopathy. We aimed to identify specific CMR features associated with MA-CMP., Methods: A retrospective cohort study of CMR scans was performed in a single centre between January 2015 and December 2020. Thirty patients with MA-CMP who had undergone CMR were identified. MA-CMP was defined as those with a history of significant methamphetamine use hospitalised with acute decompensated heart failure (other causes of cardiomyopathy excluded). A retrospective analysis of index admission CMRs was performed. All studies were performed on a 1.5 T CMR scanner., Results: The mean age of MA-CMP patients was 43.7 ± 7.5 years, and 86.7% were male. The mean left ventricular (LV) volume obtained in this cohort was consistent with severe LV dilatation (LV end-diastolic volume (334 ± 99 ml); LV end-systolic volume: 269 ± 98 ml), whilst the right ventricular (RV) volume indicated moderate-to-severe dilatation (RV end-diastolic volume: 272 ± 91 ml; RV end-systolic volume: 173 ± 82 ml). Mean LV ejection fraction (20.9 ± 9.2%) indicated severe LV dysfunction, with moderate-to-severe RV dysfunction also detected (RV ejection fraction: 29.4 ± 13.4%). 22 patients (73.3%) had myocardial late gadolinium enhancement (LGE), of which 59.1% were located in the mid-wall, with all of these involving the interventricular septum. 22.7% displayed localised regions of sub-endocardial LGE in a variety of locations, and 18.2% had transmural regions of LGE that were located in the inferior and inferolateral segments. 6 patients (20%) had intracardiac thrombus (4 LV, 2 both LV and RV)., Conclusion: MA-CMP was associated with severe biventricular dilatation and dysfunction, with a high prevalence of intraventricular thrombus. This cohort study highlights that MA-CMP patients have a high prevalence of CMR findings., (© 2022. The Author(s).)

Aim: In recent decades, the prevalence of amphetamine and methamphetamine use disorders has at least doubled in some regions/countries, with accompanying high risks of drug overdose-associated mortality. Noninvasive brain stimulation (NIBS) methods may be effective treatments. However, the comparative efficacy of the NIBS protocol for amphetamine/methamphetamine use disorder (AUD/MUD) remains unknown to date. The aim of this network meta-analysis (NMA) was to compare the efficacy and acceptability of various NIBS methods/protocols for AUD/MUD management., Methods: A frequentist model-based NMA was conducted. We included randomized controlled trials (RCTs) that investigated the efficacy of NIBS and guideline-recommended pharmacologic treatments to reduce craving severity in patients with either AUD or MUD., Results: Twenty-two RCTs including 1888 participants met the eligibility criteria. Compared with the sham/placebo group (study = 19, subjects = 891), a combination of intermittent theta burst stimulation over the left dorsolateral prefrontal cortex (DLPFC) and continuous TBS over the left ventromedial prefrontal cortex (study = 1, subjects = 19) was associated with the largest decreases in craving severity [standardized mean difference (SMD) = -1.50; 95% confidence intervals (95%CIs) = -2.70 to -0.31]. High-frequency repetitive transcranial magnetic stimulation over the left DLPFC was associated with the largest improvements in depression and quality of sleep (study = 3, subjects = 86) (SMD = -2.48; 95%CIs = -3.25 to -1.71 and SMD = -2.43; 95%CIs = -3.38 to -1.48, respectively). The drop-out rate of most investigated treatments did not significantly differ between groups., Conclusion: The combined TBS protocol over the prefrontal cortex was associated with the greatest improvement in craving severity. Since few studies were available for inclusion, additional large-scale randomized controlled trials are warranted., (© 2022 The Authors. Psychiatry and Clinical Neurosciences © 2022 Japanese Society of Psychiatry and Neurology.)