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BACKGROUND: The group-I metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in methamphetamine exposure in animals and in human cognition. Because people with methamphetamine use disorder (MUD) exhibit cognitive deficits, we evaluated mGlu5 in people with MUD and controls and tested its association with cognitive performance. METHODS: Positron emission tomography was performed to measure the total VT of [18F]FPEB, a radiotracer for mGlu5, in brains of participants with MUD (abstinent from methamphetamine for at least 2 weeks, N = 14) and a control group (N = 14). Drug use history questionnaires and tests of verbal learning, spatial working memory, and executive function were administered. Associations of VT with methamphetamine use, tobacco use, and cognitive performance were tested. RESULTS: MUD participants did not differ from controls in global or regional VT, and measures of methamphetamine use were not correlated with VT. VT was significantly higher globally in nonsmoking vs smoking participants (main effect, P = .0041). MUD participants showed nonsignificant weakness on the Rey Auditory Verbal Learning Task and the Stroop test vs controls (P = .08 and P = .13, respectively) with moderate to large effect sizes, and significantly underperformed controls on the Spatial Capacity Delayed Response Test (P = .015). Across groups, Rey Auditory Verbal Learning Task performance correlated with VT in the dorsolateral prefrontal cortex and superior frontal gyrus. CONCLUSION: Abstinent MUD patients show no evidence of mGlu5 downregulation in brain, but association of VT in dorsolateral prefrontal cortex with verbal learning suggests that medications that target mGlu5 may improve cognitive performance.

BACKGROUND: We investigate the relationship between the supply of methamphetamine and overdose death risk in Ohio. Ohio and the overall US have experienced a marked increase in overdose deaths from methamphetamine combined with fentanyl over the last decade. The increasing use of methamphetamine may be increasing the risk of overdose death. However, if people are using it to substitute away from more dangerous synthetic opioids, it may reduce the overall risk of overdose death. METHODS: Ohios Bureau of Criminal Investigations crime lab data include a detailed list of the content of drug samples from law enforcement seizures, which are used as a proxy for drug supply. We use linear regressions to estimate the relationship between the proportion of methamphetamine in lab samples and unintentional drug overdose death rates from January 2015 through September 2021. RESULTS: Relatively more methamphetamine in crime lab data in a county-month has either no statistically significant relationship with overdose death rates (in small and medium population counties) or a negative and statistically significant relationship with overdose death rates (in large population counties). Past overdose death rates do not predict future increases in methamphetamine in crime lab data. CONCLUSIONS: The results are consistent with a relatively higher supply of methamphetamine reducing the general risk of overdose death, possibly due to substitution away from more dangerous synthetic opioids. However, the supply of methamphetamine appears unrelated to the past illicit drug risk environment. The non-lethal and yet serious health effects of MA use were not explored and, thus, even if the presence of MA reduces the population-level overdose mortality rate, the rise of other adverse health effects may counteract any public health benefits of fewer deaths.

BACKGROUND: Methamphetamine use has emerged as a major risk factor for cardiovascular and cerebrovascular disease in young adults. The aim of this study was to investigate a possible association of methamphetamine use with cardioembolic stroke. METHODS AND RESULTS: We performed a retrospective study of patients with acute ischemic stroke admitted at our medical center between 2019 and 2022. All patients were screened for methamphetamine use and cardiomyopathy, defined as left ventricular ejection fraction ≤45%. Among 938 consecutive patients, 46 (4.9%) were identified as using methamphetamine. Compared with the nonmethamphetamine group (n=892), the methamphetamine group was significantly younger (52.8±9.6 versus 69.7±15.2 years; P

IntroductionMethamphetamine use is highly prevalent among men who have sex with men (MSM), but knowledge of the long-term dynamics, and how they are affected by substance use treatment, is limited. This study aimed to describe trajectories of methamphetamine use among MSM, and to evaluate the impact of treatment for any kind of substance use on frequency of methamphetamine use.MethodsThis analysis used data from a cohort of MSM in Los Angeles, CA, who participated in semi-annual study visits from 2014 to 2022. The study characterized trajectories of methamphetamine use using a continuous time multistate Markov model with three states. States were defined using self-reported frequency of methamphetamine use in the past six months: frequent (daily), occasional (weekly or less), and never. The model estimated the association between receiving treatment for any kind of substance use and changes in state of frequency of methamphetamine use.ResultsThis analysis included 2348 study visits among 285 individuals who were followed-up for an average of 4.4 years. Among participants who were in the frequent use state, 65 % (n = 26) of those who were receiving any kind of substance use treatment at a study visit had reduced their methamphetamine use at their next visit, compared to 33 % (n = 95) of those who were not receiving treatment. Controlling for age, race/ethnicity, and HIV-status, those who reported receiving current treatment for substance use were more likely to transition from occasional to no use (HR: 1.63, 95 % CI: 1.10-2.42) and frequent to occasional use (HR: 4.25, 95 % CI: 2.11-8.59) in comparison to those who did not report receiving current treatment for substance use.ConclusionsFindings from this dynamic modeling study provide a new method for assessing longitudinal methamphetamine use outcomes and add important evidence outside of clinical trials that substance use treatment may reduce methamphetamine use.

Craving is central to methamphetamine use disorder (MUD) and both characterizes the disease and predicts relapse. However, there is currently a lack of robust and reliable biomarkers for monitoring craving and diagnosing MUD. Here, we seek to identify a neurobiological signature of craving based on individual-level functional connectivity pattern differences between healthy control and MUD subjects. We train high-density electroencephalography (EEG)-based models using data recorded during the resting state and then calculate imaginary coherence features between the band-limited time series across different brain regions of interest. Our prediction model demonstrates that eyes-open beta functional connectivity networks have significant predictive value for craving at the individual level and can also identify individuals with MUD. These findings advance the neurobiological understanding of craving through an EEG-tailored computational model of the brain connectome. Dissecting neurophysiological features provides a clinical avenue for personalized treatment of MUD.

The authors describe a case of nylon foil implant infection caused by Fusarium brachygibbosum , and Lomentospora prolificans following medial orbital wall fracture repair in the setting of postoperative nasal methamphetamine use. A 61-year-old male presented with OS pain and swelling after a physical assault on his face. A CT of maxillofacial bones without contrast showed a moderately comminuted fracture of the medial wall of the left orbit with depression of fracture fragments into the left ethmoid air cells. Six days after repair of the medial wall fracture, the patient returned with a new onset headache, OS pain, and swelling to the left medial canthal area. He reported snorting methamphetamine approximately 48 hours before his current presentation. CT imaging showed fat stranding and soft tissue density in the extraconal space adjacent to the left medial rectus muscle and chronic fracture deformity of lamina papyracea with approximately 4 mm of medial displacement of the fracture fragments. The patient showed little clinical improvement after 48 hours of intravenous antibiotics, which led to the removal of the nylon foil implant by a left orbitotomy. Intraoperative tissue cultures grew coagulase-negative Staphylococcus , F. brachygibbosum , and Lomentospora (Scedosporium) prolificans . The patient was subsequently transitioned to oral clindamycin 600 mg three times daily and voriconazole 200 mg two times daily. To the authors' knowledge, this is the first case report to document an association between snorted methamphetamine and a fungal infection of an orbital implant.

BACKGROUND: Illicitly manufactured fentanyls and stimulants are implicated in the escalating US mortality from drug overdose. San Francisco, California (SF) has seen declining fentanyl injection while smoking has increased. Beliefs and behaviors surrounding this development are not well understood. METHODS: The study used rapid ethnography to explore fentanyl and methamphetamine use in SF. The team conducted semi-structured interviews (n = 34) with participants recruited from syringe service programs. Video-recorded smoking sequences (n = 12), photography and daily field notes supplemented interview data. RESULTS: Difficulty injecting and fear of overdose motivated transitions from injecting to smoking. Fentanyl was extremely cheap-$10/gram-with variability in quality. Foil was the most commonly used smoking material but glass bubbles, bongs and dabbing devices were also popular. No reliable visible methods for determining fentanyl quality existed, however, participants could gauge potency upon inhalation, and developed techniques to regulate dosage. Several participants reported at least hourly use, some reporting one or more grams of daily fentanyl consumption. Smoking was also very social, with people sharing equipment, drugs and information. Participants raised concerns about hygiene and overdose risk to others arising from shared equipment. Reportedly potent fentanyl residue accumulated on smoking materials and was commonly shared/traded/stolen or consumed accidentally with diverse preferences for its use. CONCLUSION: Our data highlight fentanyl residue as a new overdose risk with potential mismatch between the potency of the residual drug and the recipients tolerance. Further, large doses of fentanyl are being consumed (estimated at approximately 50 mg of pure fentanyl/day). Smoking fentanyl has potential health benefits over injecting and may be protective against overdose, but substantial uncertainty exists. However, SF overdose mortality hit a record high in 2023. Recommendations to reduce fentanyl smoking overdose risks through pacing, greater awareness of dosages consumed and checking tolerance of residue recipients are potentially viable interventions deserving further exploration.

INTRODUCTION: While known animal exposures to human drugs of abuse (DA) were previously considered relatively uncommon in veterinary medicine, the trends are changing. Marijuana and amphetamines are among the 20 toxicants most frequently consulted about with the Pet Poison Helpline. When such exposures occur, they are typically considered emergencies. METHODS: This retrospective study describes confirmed cases of DA exposure in pets from the California Animal Health and Food Safety Laboratory System (CAHFS), 2013-2023. RESULTS: Fifty-seven samples tested positive for DA through liquid chromatography with tandem mass spectrometry analysis (qualitative method). In 75% (43/57) of the DA screen tests, the detected drugs included amphetamine-type stimulants and metabolites (methamphetamine, amphetamine, or both). In 47% (27/57) of cases, a combination of more than one drug group was found. Most cases were diagnosed from a urine specimen. In at least 32% (18/57) of cases, the samples were submitted due to suspicions of animal cruelty, and at least 41% (23/57) of the patients were deceased when the samples were submitted. DISCUSSION: More studies on the prevalence of illicit drugs in small animals, using confirmatory testing, are warranted to fully understand the significance of this emerging toxicological hazard in veterinary medicine.

ObjectiveMethamphetamine and cannabis are two widely used, and frequently co-used, substances with possibly opposing effects on the central nervous system. Evidence of neurocognitive deficits related to use is robust for methamphetamine and mixed for cannabis. Findings regarding their combined use are inconclusive. We aimed to compare neurocognitive performance in people with lifetime cannabis or methamphetamine use disorder diagnoses, or both, relative to people without substance use disorders.Method423 (71.9% male, aged 44.6 ± 14.2 years) participants, stratified by presence or absence of lifetime methamphetamine (M-/M+) and/or cannabis (C-/C+) DSM-IV abuse/dependence, completed a comprehensive neuropsychological, substance use, and psychiatric assessment. Neurocognitive domain T-scores and impairment rates were examined using multiple linear and binomial regression, respectively, controlling for covariates that may impact cognition.ResultsGlobally, M+C+ performed worse than M-C- but better than M+C-. M+C+ outperformed M+C- on measures of verbal fluency, information processing speed, learning, memory, and working memory. M-C+ did not display lower performance than M-C- globally or on any domain measures, and M-C+ even performed better than M-C- on measures of learning, memory, and working memory.ConclusionsOur findings are consistent with prior work showing that methamphetamine use confers risk for worse neurocognitive outcomes, and that cannabis use does not appear to exacerbate and may even reduce this risk. People with a history of cannabis use disorders performed similarly to our nonsubstance using comparison group and outperformed them in some domains. These findings warrant further investigation as to whether cannabis use may ameliorate methamphetamine neurotoxicity.

Intact executive functions are required for proper performance of cognitive tasks and relies on balance of excitatory and inhibitory (E/I) transmission in the medial prefrontal cortex (mPFC). Hypofrontality is a state of decreased activity in the mPFC and is seen in several neuropsychiatric conditions, including substance use disorders. People who chronically use methamphetamine (meth) develop hypofrontality and concurrent changes in cognitive processing across several domains. Despite the fact that there are sex difference in substance use disorders, few studies have considered sex as a biological variable regarding meth-mediated hypoactivity in mPFC and concurrent cognitive deficits. Hypofrontality along with changes in cognition are emulated in rodent models following repeated meth administration. Here, we used a meth sensitization regimen to study sex differences in a Temporal Order Memory (TOM) task following short (7 days) or prolonged (28 days) periods of abstinence. GABAergic transmission, GABAA receptor (GABAAR) and GABA Transporter (GAT) mRNA expression in the mPFC were evaluated with patch-clamp recordings and RT-qPCR, respectively. Both sexes sensitized to the locomotor activating effects of meth, with the effect persisting in females. After short abstinence, males and females had impaired TOM and increased GABAergic transmission. Female rats recovered from these changes after prolonged abstinence, whereas male rats showed enduring changes. In general, meth appears to elicit an overall decrease in GABAAR expression after short abstinence; whereas GABA transporters are decreased in meth female rats after prolonged abstinence. These results show sex differences in the long-term effects of repeated meth exposure and suggest that females have neuroprotective mechanisms that alleviate some of the meth-mediated cognitive deficits. [ABSTRACT FROM AUTHOR]

Background and Objectives: Although concurrent stimulant use is common among people with opioid use disorder (OUD), there is little evidence on its impacts on opioid agonist therapy (OAT) outcomes. This study sought to determine the impact of baseline methamphetamine/amphetamine use on discontinuation of OAT among individuals with prescription‐type OUD (POUD) initiating methadone or buprenorphine/naloxone as part of a pragmatic randomized trial in Canada. Methods: Secondary analysis of a pan‐Canadian pragmatic trial conducted between 2017 and 2020 comparing supervised methadone versus flexible take‐home dosing buprenorphine/naloxone models of care. Cox proportional hazard models were used to evaluate the effect of baseline methamphetamine/amphetamine use (measured by urine drug test [UDT]) on two discontinuation outcomes (i.e., assigned OAT discontinuation, any OAT discontinuation). Results: Two hundred nine (n = 209) participants initiated OAT, of which 96 (45.9%) had positive baseline methamphetamine/amphetamine UDT. Baseline methamphetamine/amphetamine use was associated with shorter median times in assigned OAT (21 vs. 168 days, hazard ratio [aHR] = 2.45, 95% confidence interval [CI] = 1.60–3.76) and any OAT (25 days vs. 168 days, aHR = 2.06, CI = 1.32–3.24). No interaction between methamphetamine/amphetamine and assigned OAT was observed for either outcome (p >.05). Conclusion and Scientific Significance: This study offers novel insights on the impact of methamphetamine/amphetamine use on OAT outcomes among people with POUD. Methamphetamine/amphetamine use was common and was associated with increased risk of OAT discontinuation. Supplementary interventions, including treatment for stimulant use, are needed to improve retention in OAT and optimize treatment outcomes in this population. [ABSTRACT FROM AUTHOR]

Background: Substance use carries a wide range of negative consequences, impacting both the individual using the substances and others. In recent years, there have been multiple efforts to assess the harm caused by drugs and to rank them, with each taking a distinctive approach to the matter. Objectives: This study seeks to introduce a new model for assessing the harm index and ranking of drugs. Methods: This prospective study involved the evaluation of 277 male drug users, assessing substance use harm on four separate occasions throughout the span of 1 year. Various aspects of harm were quantified through the utilization of the Duke Health Profile (DUKE) and the Addiction Severity Index (ASI) questionnaire. The pharmaceutical properties of each drug were incorporated into the study. The relationship between the combined variables in a mixed statistical model was determined at a significance level of.05 using the Rsoftware. This procedure facilitated the establishment of models and the definition of harm index ranges for each substance. Result: The results indicated that heroin had the highest harm index at 71.2 (95% CI69.6–72.8), while pure methadone scored the lowest at 36.5 (95% CI31.7–41.7), along with methadone combined with methamphetamine, which scored 35 (95% CI33–37.1). Conclusion: The variables utilized in this study can help estimate the approximate harm index range for both traditional and novel substances. Furthermore, the harm model designed in this study has the capability to predict the extent of harm to a drug user. [ABSTRACT FROM AUTHOR]

Addictive, illicit drugs pose a high threat of relapse. The deaths related to illicit drugs have substantially increased in the last decade. Globally, the illicit drug trade poses a significant challenge to public health and law enforcement. It is essential to utilize advanced analytical methodologies that can characterize illegal substances precisely to monitor these drugs. Surfaced-enhanced Raman spectroscopy (SERS) has become a valuable tool, providing distinct capabilities for analyzing illegal substances. Surface enhancement enables far more sensitive detection and identification of illicit drugs by suppressing the fluorescence and enhancing the Raman signals. In this regard, a simple method with limited sample processing has been established to characterize illicit drugs that include methamphetamine (MAMP) (ice), bhang, marijuana (cannabis), opium, and diacetylmorphine (heroin). Moreover, principal component analysis (PCA) was employed for the identification of the characteristic SERS spectral features of these drugs. This article examines the potential application of SERS in the characterization of illicit substances, focusing on its ability to contribute significantly to law enforcement and forensic investigation. [ABSTRACT FROM AUTHOR]

Methamphetamine (MA) is a neurological drug, which is harmful to the overall brain cognitive function when abused. Based on this property of MA, people can be divided into those with MA abuse and healthy people. However, few studies to date have investigated automatic detection of MA abusers based on the neural activity. For this reason, the purpose of this research was to investigate the difference in the neural activity between MA abusers and healthy persons and accordingly discriminate MA abusers. First, we performed event-related potential (ERP) analysis to determine the time range of P300. Then, the wavelet coefficients of the P300 component were extracted as the main features, along with the time and frequency domain features within the selected P300 range to classify. To optimize the feature set, F_score was used to remove features below the average score. Finally, a Bidirectional Long Short-term Memory (BiLSTM) network was performed for classification. The experimental result showed that the detection accuracy of BiLSTM could reach 83.85%. In conclusion, the P300 component of EEG signals of MA abusers is different from that in normal persons. Based on this difference, this study proposes a novel way for the prevention and diagnosis of MA abuse. [ABSTRACT FROM AUTHOR]

Evidence from a number of paradigms suggests that methamphetamine use is associated with increased risk for the development of Parkinson's disease and parkinsonism, and that it may be associated with the premature development of Parkinson's disease. Prevalence of Parkinson's disease and parkinsonism is greater in both methamphetamine users and people who previously used methamphetamine, and evidence from animal studies provides a plausible mechanism for this observation. Despite this increased risk, Parkinson's disease is rarely diagnosed in methamphetamine users. Reasons for this may include under‐detection, premature mortality, and individual and substance use characteristics which moderate the risk, including higher rates of smoking. Clinicians should be vigilant to signs and symptoms of Parkinson's disease and parkinsonism in methamphetamine users. [ABSTRACT FROM AUTHOR]

Combined use of fentanyl and methamphetamine (FENT + METH) has increased in recent years and has been documented in a growing number overdose deaths each year. The impact of FENT + METH on behavior and neurobiology is not well understood. In this study, male and female Long Evans rats were tested on a limited access, fixed ratio 1 self‐administration schedule for increasing doses (1.25–5 μg/kg/infusion; iv) of fentanyl, with and without a single dose (0.1 mg/kg/infusion; iv) of methamphetamine, for 15 days. FENT + METH abolished dose responsiveness to fentanyl in all rats and accelerated intake in males, resulting in patterns of responding that may be more likely to result in adverse effects. Ex vivo slice voltammetry in the nucleus accumbens core showed decreases in dopamine release and reuptake (Vmax) following FENT + METH exposure, compared with saline, fentanyl, and methamphetamine alone groups at baseline parameters. Further, significant decreases in dopamine release were observed across a range of stimulation intensities following FENT + METH exposure. Overall, male and female rats displayed sex‐specific behavioral and neurobiological responses to FENT + METH exposure, with males displaying increased vulnerability. [ABSTRACT FROM AUTHOR]

The ability to maintain and manipulate sequential information in working memory, referred to as sequential working memory, plays a vital role in our daily life. While research has shown that methamphetamine abuse affects the neural substrates and the overall functioning of working memory, its specific impact on sequential working memory remains unclear. In this study, we asked 62 abstinent methamphetamine-dependent participants and 59 control participants to complete a digit ordering task in which they saw four digits one-by-one over time and subsequently rearranged them in ascending order. The four digits were presented either randomly in the experimental condition or in ascending order in the control condition. Resul ts show that methamphetamine-dependent participants performed worse than the controls in the experimental condition in which sequential working memory was needed to complete the task, but not in the control condition in which only short-term memory was needed. This finding demonstrates that methamphetamine abuse impairs sequential working memory. [ABSTRACT FROM AUTHOR]

Background: Individuals using methamphetamine (METH) may experience psychosis, which usually requires aggressive treatment. Studies of the neural correlates of METH-associated psychosis (MAP) have focused predominantly on the default mode network (DMN) and cognitive control networks. We hypothesize that METH use alters global functional connections in resting-state brain networks and that certain cross-network connections could be associated with psychosis. Methods: We recruited 24 healthy controls (CRL) and 54 men with METH use disorder (MUD) who were then divided into 25 without psychosis (MNP) and 29 with MAP. Psychotic symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS), evaluating (1) large-scale alterations in regional-wise resting-state functional connectivity (rsFC) across 11 brain networks and (2) associations between rsFC and psychotic symptom severity. Results: The MUD group exhibited greater rsFC between the salience network (SN)-DMN, and subcortical network (SCN)-DMN compared to the CRL group. The MAP group exhibited decreased rsFC in the sensory/somatomotor network (SMN)-dorsal attention network (DAN), SMN-ventral attention network (VAN), SMN-SN, and SMN-auditory network (AN), whereas the MNP group exhibited increased rsFC in the SMN-DMN and the frontoparietal network (FPN)-DMN compared to CRL. Additionally, the MAP group exhibited decreased rsFC strength between the SMN-DMN, SMN-AN, SMN-FPN, and DMN-VAN compared to the MNP group. Furthermore, across the entire MUD group, the PANSS-Positive subscale was negatively correlated with the DMN-FPN and FPN-SMN, while the PANSS-Negative subscale was negatively correlated with the DMN-AN and SMN-SMN. Conclusion: MUD is associated with altered global functional connectivity. In addition, the MAP group exhibits a different brain functional network compared to the MNP group. [ABSTRACT FROM AUTHOR]

Introduction: Polydrug use in the context of chemsex is commonplace among gay, bisexual, and other men-who-have-sex-with-men (GBMSM). This study aimed to examine the differences in experiences of physical, social, and psychological harms, as well as mental ill-health among GBMSM who use different combinations of methamphetamine and gamma-hydroxybutyric acid/gamma-butyrolactone (GHB/GBL) during chemsex. Method: Adult GBMSM participants who had experience of chemsex in the past 12 months participated in a cross-sectional online survey in Taiwan and self-reported their sociodemographic background, sexual behaviours, mental health, and experiences of harm following a chemsex session. We used univariable and multivariable logistic regression to assess the different experiences of harm and mental ill-health among GBMSM who engaged in chemsex without using methamphetamine, used methamphetamine but not GHB/GBL, and who used both drugs. Results: Out of 510 participants who completed all items included in the analysis, 24.1% engaged in chemsex without using methamphetamine, 36.9% used methamphetamine but not GHB/GBL, and 39.0% used both drugs. Eighty five percent of men who used both methamphetamine and GHB/GBL reported at least one kind of social harm after a chemsex session, such as missing dates or appointments, or appearing "high" at work, followed by used methamphetamine but not GHB/GBL (69.7%) and those without using methamphetamine (37.4%). After controlling for polydrug and frequency of drug use in the multivariable logistic regression, those who used methamphetamine but not GHB/GBL and those who used both drugs were more likely to report experiencing physical and psychological harms compared to those who did not use methamphetamine (p < 0.003). Conclusion: GBMSM who used both methamphetamine and GHB/GBL in a chemsex context were more likely to report experience of harms than those who only used a single chemsex drug or engaged in chemsex without methamphetamine or GHB/GBL. Harm reduction should focus on both preventing HIV and STI transmission and on minimising psychosocial harm to GBMSM, with varying impacts depending on drug use. [ABSTRACT FROM AUTHOR]

Working memory difficulties are common, debilitating, and may pose barriers to recovery for people who use methamphetamine. Yet, little is known regarding the neural dysfunctions accompanying these difficulties. Here, we acquired cross‐sectional, functional magnetic resonance imaging while people with problematic methamphetamine‐use experience (MA+, n = 65) and people without methamphetamine‐use experience (MA−, n = 44) performed a parametric n‐back task (0‐back through 2‐back). Performance on tasks administered outside of the scanner, together with n‐back performance, afforded to determine a latent dimension of participants' working memory ability. Behavioural results indicated that MA+ participants exhibited lower scores on this dimension compared to MA− participants (d = −1.39, p <.001). Whole‐brain imaging results also revealed that MA+ participants exhibited alterations in load‐induced responses predominantly in frontoparietal and default‐mode areas. Specifically, while the MA− group exhibited monotonic activation increases within frontoparietal areas and monotonic decreases within default‐mode areas from 0‐back to 2‐back, MA+ participants showed a relative attenuation of these load‐induced activation patterns (d = −1.55, p <.001). Moreover, increased activations in frontoparietal areas from 0‐ to 2‐back were related to greater working memory ability among MA+ participants (r =.560, p =.004). No such effects were observed for default‐mode areas. In sum, reductions in working memory ability were observed alongside load‐induced dysfunctions in frontoparietal and default‐mode areas for people with problematic methamphetamine‐use experience. Among them, load‐induced activations within frontoparietal areas were found to have a strong and specific relationship to individual differences in working memory ability, indicating a putative neural signature of the working memory difficulties associated with chronic methamphetamine use. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to measure trajectories of craving for methamphetamine during the course of pharmacotherapy trials for methamphetamine use disorder. Design, setting and participants: Craving trajectories were identified using Group‐Based Trajectory Modeling. The association of craving trajectories with drug use trajectories was examined using a dual trajectory model. Association of craving trajectories with other health and social outcomes was also examined. The study used pooled data from five randomized controlled pharmacotherapy trials for methamphetamine use disorder. A total of 866 adults with methamphetamine use disorder participated in randomized controlled pharmacotherapy trials. Measurement: Craving was assessed weekly using the Brief Substance Craving Scale. Drug use was assessed using urine toxicology. Alcohol‐ and drug‐related problems, as well as psychiatric, medical, legal, employment and relationship problems, were measured using the Addiction Severity Index. Findings: A three‐trajectory model with high, medium and low craving trajectories was selected as the most parsimonious model. Craving trajectories were associated with methamphetamine use trajectories in the course of trial; 88.4% of those in the high craving trajectory group had a consistently high frequency of methamphetamine use compared with 18.7% of those in the low craving group. High craving was also associated with less improvement in most other outcomes and higher rate of dropout from treatment. In turn, low craving was associated with a rapidly decreasing frequency of methamphetamine use, greater improvement in most other outcomes and a lower rate of dropout. Participants on modafinil daily and ondansetron 1 mg twice daily were less likely to be in the high craving group compared with those on placebo. Conclusions: Trajectories of methamphetamine craving in the course of clinical trials for methamphetamine use disorder appear to be both highly variable and strongly associated with greater frequency of drug use, other drug‐related outcomes and dropout from trials. Two medications, modafinil daily and ondansetron at a dose of 1 mg two times daily, appear to be associated with greater reduction in craving in the course of treatment compared with placebo. A decrease in methamphetamine craving shows promise as an early indicator of recovery from methamphetamine use disorder. [ABSTRACT FROM AUTHOR]

Background and aims: A 12‐week placebo‐controlled, sequential parallel Accelerated Development of Additive Pharmacotherapy Treatment for Methamphetamine Use Disorder (ADAPT‐2) trial evaluated the effects of extended‐release injectable naltrexone plus extended‐release oral bupropion (NTX + BUPN) on methamphetamine (MA) use over two stages. This study reports on the previously unpublished stage 2 MA use in participants randomized at stage 1 to receive NTX + BUPN through both stages compared with those assigned to placebo. Design: This is a secondary analysis of the US National Institute on Drug Abuse (NIDA) ADAPT‐2 network trial. Setting: The parent ADAPT‐2 trial was carried out across multiple NIDA Clinical Trials Network (CTN) sites in the United States. Participants: This analysis includes 403 people with MA use disorder who participated in the ADAPT‐2 CTN trial. Intervention and comparator: NTX + BUPN was compared with placebo over the course of the trial. Measurement MA use was measured by urine drug screens conducted twice weekly for 12 weeks, then once in week 13 and once in week 16 post‐treatment follow‐up. Findings Participants on NTX + BUPN in stage 1 showed an additional 9.2% increase [95% confidence interval (CI), 0.09%–17.9%, P = 0.038] during stage 2 in their probability of testing negative for MA, with a total increase of 27.1% (95% CI, 13.2%–41.1%, P < 0.001) over the full 12 weeks of treatment. In contrast, participants on placebo in both stages increased in probability of testing MA‐negative by a total of 11.4% (95% CI, 4.1%–18.6%, P = 0.002) over all 12 weeks. The 12‐week increase among participants on NTX + BUPN was significantly greater—by 15.8% (95% CI, 4.5%–27.0%, P = 0.006)—than the increase among those on placebo. Conclusion: For people with methamphetamine (MA) use disorder receiving treatment with extended‐release injectable naltrexone plus extended‐release oral bupropion (NTX + BUPN), continued treatment with NTX + BUPN after 6 weeks is associated with additional reductions in MA use up to 12 weeks. [ABSTRACT FROM AUTHOR]

Introduction Methods Findings Discussion and Conclusions While research with sexual minority men (SMM) has focused on disparities related to HIV, substance use and mental health, synergistic psychosocial pathways driving these epidemics remain underexplored. We used syndemic theory to assess how psychosocial factors sustain methamphetamine use and hinder recovery efforts for SMM living with HIV.A triangulation of network analyses and constructivist grounded theory approaches is utilised to elucidate pathways through which psychosocial factors influence methamphetamine use among this population. Survey data (N = 129) are used for quantitative analyses and a purposive sub‐sample (n = 24) was recruited for semi‐structured interviews for qualitative analyses.The network analysis revealed two statistically significant bivariate associations: between post‐traumatic stress disorder and depression symptoms (b = 0.37, SD = 0.07, 95% confidence interval [0.23, 0.49]) and between depression symptoms and negative affect (b = 0.26, SD = 0.07, 95% confidence interval [0.12, 0.38]). Findings from the constructivist grounded theory analysis supplement the network analysis by offering a nuanced take on how negative affect, post‐traumatic stress disorder, and depression symptoms operate synergistically to promote methamphetamine use and impede recovery efforts.Participants relay experiences of using methamphetamine to cope with these psychosocial factors through avoidance, escapism, mood elevation, and numbing of emotions. Findings suggest that centring these psychosocial factors may inform more effective, holistic interventions for this high‐priority population. [ABSTRACT FROM AUTHOR]

Background and Objective: Methamphetamine is a highly addictive drug associated with severe psychosocial consequences and is extensively abused. This study aimed to determine the effects of four weeks of aerobic exercise and berberine supplementation on the expression of dopamine 5 receptor and poly (adenosin diphosphat [ADP]-ribose polymerase (PARP) genes in the heart tissue of methamphetamine-exposed rats. Methods: In this experimental study, 30 female Wistar rats were randomly allocated into five groups of six: Control, methamphetamine, methamphetamine + aerobic exercise, methamphetamine + berberine, and methamphetamine + aerobic exercise + berberine. Intraperitoneal injections of methamphetamine (10 mg/kg) and aerobic exercise and berberine consumption (100 mg/kg) were administered for 4 weeks during the withdrawal period. The expression levels of dopamine 5 receptor and PARP genes was measured using real-time polymerase chain reaction (PCR). Results: There was no significant difference in PARP gene expression between the methamphetamine group (1.02±0.65) and the control group (1.02±0.24). Similarly, there was no significant difference in dopamine 5 receptor gene expression between the methamphetamine group (5.74±4.94) and the control group (4.76±2.63). The expression levels of PARP and dopamine 5 receptor genes following exercise (1.01±0.55 and 4.30±1.96, respectively), berberine supplementation (0.61±0.25 and 2.97±1.45, respectively), and the combined intervention (0.67±0.30 and 3.43±1.87, respectively) showed no significant differences between the groups. Conclusion: Short-term methamphetamine induction did not induce significant changes in the expression of dopamine 5 receptor and PARP genes in the hearts of methamphetamine-exposed rats [ABSTRACT FROM AUTHOR]