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Introduction: Adherence to Highly Active Antiretroviral Therapy (HAART) is critical in controlling HIV. Poor medication adherence may lead to higher disease mortality, increased HIV spread, and transmission of drug-resistant strains. Identifying the specific factors that contribute to suboptimal medication adherence in people with HIV is crucial for developing effective, personalized interventions., Methods: This study conducted a cross-sectional analysis by enrolling individuals over 18 years of age with HIV at a single clinic in Taipei, Taiwan, from December 2018 to November 2020. Participants completed a questionnaire that collected demographic data, recreational drug use, comorbidities, and history of sexually transmitted infections (STIs). The Medication Adherence Report Scale (MARS-5) was utilized to assess treatment adherence. A multiple logistic regression model was applied to identify the factors influencing adherence., Results: A total of 831 PWH were included in the analysis. After controlling for demographics, comorbidities, and recreational drug use, independent risk factors associated with poor adherence among PWH include the presence of a depressive disorder (AOR:2·887, 95% CI:1·461-5·703, p = 0·002), a history of acquired gonorrhea (AOR:2·026, 95% CI:1·079 - 3·803, p = 0·028), methamphetamine use within past three months (AOR:2·073, 95% CI:1·172-3·665, p = 0·012), HIV-1 RNA ≥ 40 copies/ml (AOR:5·221, 95% CI:2·976-9·157, p < 0·001) and younger age (AOR:0·959, 95% CI:0·932-0·988, p = 0·006)., Conclusions: To enhance HIV treatment adherence, targeted efforts are essential for PWH who are young, have used methamphetamine in the past three months, are experiencing depressive disorders, or have previously acquired gonorrhea., Competing Interests: Declarations. Competing interests: All 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., (© 2024. The Author(s).)

Drug consumption estimates are traditionally based on surveys or information from police seizures. Alternatively, residues of illicit drugs in untreated wastewater (influent) can be used to calculate mass loads and subsequently estimate drug consumption in the community throughout the week. For this purpose, wastewater is commonly sampled for seven consecutive days within the Sewage analysis CORe group Europe (SCORE), while other sampling schemes may be implemented in long-term studies outside this consortium. The current study demonstrates how sampling frequency of illicit drug residues in the influent of wastewater treatment plants (WWTPs) affects the derived weekly average. Thirty WWTPs were sampled over the course of 12 years and influents were analyzed for five drugs (metabolites): 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine, amphetamine, benzoylecgonine (a metabolite of cocaine), and 11-nor-9-Carboxy tetrahydrocannabinol (THC-COOH). Subsequently, small and large WWTPs were grouped with a threshold of 100,000 inhabitants. After data curation, standardized loads were calculated (mg/d per 1000 inhabitants). Weekly averages of loads of the drug residues were calculated based on six scenarios (sampling one to six weekdays) and compared to the weekly average in the control situation (sampling seven weekdays) in a Monte Carlo simulation. Results indicate that drug residues with more dynamic loads over a week require more frequent sampling. The analysis illustrates that a decreased sampling frequency (4 or 5 days per week) still leads to a representative weekly average for all drugs tested when a deviation up to a factor of 1.25 is deemed acceptable. However, knowledge on typical levels is necessary to define outliers. We therefore recommend to study dynamics in drug residue loads for WWTPs before reducing sampling frequency in long term monitoring programs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Evidence suggests that individuals who use methamphetamine are at a significantly higher risk of developing psychosis compared to non-users. This study aims to examine the rate of psychosis among methamphetamine users and to investigate factors related to methamphetamine-associated psychosis (MAP). Two thousand ninety-eight (2,098) individuals with methamphetamine use were admitted to outpatient care. Available admissions data included clinical interviews, the Addiction Profile Index (API), and API-clinical forms. MAP was identified in 267 (12.7%) participants. Our data analysis found significant sociodemographic, clinical, and personality differences between MAP and non-MAP cohorts on admission. Multivariate regression analysis revealed that older age (OR = 1.049), younger age of substance use onset (OR = 0.960), more frequent MA use (OR = 1.622), being single (OR = 1.974), lower education (OR = 0.46), increased number of withdrawal symptoms (OR = 1.100), higher lack of anger control scores (OR = 1.422), higher lack of assertiveness scores (OR = 1.396), and higher anxiety scores (OR = 1.715) were significantly associated with MAP. Although factors identified in this study represent state (on admission) rather than stable characterological traits, these results may nonetheless help us better characterize contextual factors associated with MAP in an outpatient population.

Background: Drug addiction is closely related to the dysregulation of complex neural circuits. However, the neural connections underlying the symptoms of methamphetamine (METH)-induced addiction have yet to be elucidated., Methods: We conducted ΔFosB (Delta FBJ murine osteosarcoma viral oncogene homolog B) associated immunofluorescence and electrophysiological recording experiments to measure neural activity of paraventricular thalamus (PVT) neurons in METH treated mice. Then, the METH-mediated conditional place preference (CPP) behaviors were evaluated after chemogenetic manipulation of PVT neurons. Additionally, the neural projection from PVT to medial prefrontal cortex (mPFC) was verified through Adeno-associated virus (AAV) mediating neural tracing method, and its role on METH-mediated CPP behaviors was determined using chemogenetic and neural ablation strategies., Results: We found that glutamatergic neurons in PVT were activated by METH. Activating the glutamatergic neurons in PVT promoted the METH-mediated CPP behaviors, while inhibiting these neurons attenuated the CPP behaviors. Moreover, we observed PVT neurons showed robust neuronal projections to mPFC, activation of the mPFC→projecting neurons in PVT or the afferent terminals in mPFC derived from PVT enhanced METH-mediated CPP performance, and ablating the mPFC neurons receipting neural projection from PVT impeded the METH-mediated CPP phenotype., Limitations: The underlying molecular mechanism of the dysfunctional PVT neurons after METH treatment and the PVT neurons regulating the activity of mPFC target neurons remains unclear., Conclusions: These results shed light on that PVT is a key METH addiction-controlling nucleus, and PVT → mPFC projection regulated METH-mediated CPP behavior, which could serve as a vital pathway for morbidity and treatment for METH-mediated addiction., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chronic exposure to methamphetamine (METH) has been suggested to cause METH use disorder and severe cognitive impairment. Paeoniflorin (PF) is a monoterpenoid glycoside with various beneficial effects, including anti-inflammatory, antioxidant and antidepressant. The current study was designed to investigate the effect of PF (30 mg/kg, i.p.) on the rewarding effect of METH (2.5 mg/kg, i.p.) and the associated cognitive impairment, using the animal model of conditioned place preference, new location reorganization test, new object reorganization test and Y-maze test. METH induced conditioned place preference, accompanied by increased expression of synapse-associated proteins in the ventral target areas (VTA) and nucleus accumbens (NAc). In addition, METH induced significant cognitive impairment and decreased the expression of synapse-associated proteins in the hippocampus (Hip). Administration of PF decreased the rewarding effect of METH and the expression of synapse-associated proteins in the VTA or NAc. PF was also effective to improve METH-induced cognitive impairment by upregulating the expression of synapse-associated proteins in the Hip. Therefore, PF could be a potential agent for the treatment of METH use disorder and the associated cognitive impairment., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: This study (1) estimated changes in anxiety and depression throughout 3 years in a community-recruited cohort who use methamphetamine and (2) modelled whether these changes were associated with patterns of methamphetamine use or other time-varying or fixed covariates., Design, Setting and Participants: We used a longitudinal analysis using data derived from surveys conducted between August 2016 and March 2020, set in metropolitan and rural locations in Victoria, Australia. Participants comprised a total of 849 adults with regular methamphetamine use history at baseline, recruited for the prospective VMAX study via snowball and respondent-driven sampling., Measurements: Anxiety and depression symptoms were measured using the Generalized Anxiety Disorder (GAD)-7 and the Patient Health Questionnaire (PHQ)-9 instruments. Frequency of methamphetamine use was measured by self-reported number of days per week participants used any form of methamphetamine in the past month., Findings: Changes in anxiety and depression symptom scores were associated with change in route of administration from non-injecting to injecting [adjusted coefficient (adj. coeff.) = 1.44, 95% confidence intervals (CI) = 0.39, 2.48, adj. coeff. = 1.49, 95% CI = 0.39, 2.58], change in severity of dependence for methamphetamine (adj. coeff. = 0.29, 95% CI = 0.21, 0.37, adj. coeff. = 0.34, 95% CI = 0.26, 0.42), starting treatment for drugs other than methamphetamine (adj. coeff. = -2.21, 95% CI = -3.70, -0.73, adj. coeff. = -2.09, 95% CI = -3.60, -0.58) and other covariates., Conclusions: Among regular methamphetamine users in Australia, changes in anxiety or depression scores are associated with changes in route of administration, dependence severity and starting treatment for other drugs, but do not appear to be associated with frequency of methamphetamine use., (© 2024 Society for the Study of Addiction.)

Methamphetamine (METH), a stimulant that is extremely addictive, directly affects the central nervous system. METH's abuse and consumption are directly linked to mental illnesses, psychosis, and behavioral and cognitive impairments. It may disrupt the reward system and dopaminergic transmission. METH's rewarding qualities are associated with a rise in dopamine. Additionally, cannabidiol (CBD), one of the primary cannabinoid components of the cannabis plant, significantly affects dopaminergic transmission and may aid in reward- and addiction-related behaviors. To shed light on the role of the D2-like dopamine receptor (D2R) in the hippocampal dentate gyrus (DG), the present study examined the effects of CBD on the acquisition and expression of the conditioned place preference (CPP) induced by METH. The function of D2R was ascertained by delivering Sulpiride microinjections, as a D2R antagonist Sulpiride (0.25, 1, and 4 μg/0.5 μL DMSO12%) into the DG. Moreover, an intracerebroventricular injection of CBD at a dose of 10 μg/5 μL for CPP acquisition and 50 μg/5 μL for CPP expression was given to rats. According to the current research, CBD dramatically reduced the acquisition and expression of CPP resulting from METH. However, Sulpiride suppressed the effect of CBD on METH-induced CPP acquisition and expression, with a greater impact on expression experiments. Ultimately, this study proposed that the expression experiment of METH-induced CPP appears to be heavily dependent on D2R in the DG., Competing Interests: Declarations Conflict of Interest The authors of this article do not have any personal or financial interests that could potentially influence the content of the article., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Psychoactive substances abuse is a global issue, with the methamphetamine (METH) being the most used and produced illicit substance in recent years. METH has been recognized as emerging contaminants in aquatic ecosystems. Research on the removal of METH from surface water is still lacking in-depth exploration. The effects of key aqueous environmental factors on the photodegradation of METH were investigated in this study. NO₃ ⁻ , Fe 3+ and dissolved organic matter (DOM) enhanced the photodegradation of METH, respectively, with degradation rates increasing as their concentrations increased. When HCO₃ ⁻ coexisted with NO₃ ⁻ , it exhibited dual effects on METH photodegradation: low concentrations inhibited the process, whereas high concentrations promoted it. The primary photodegradation products of METH, such as OH-METH, (OH) 2 -METH, AMP and NO 2 -OH-METH, were identified. The latter two compounds were newly discovered in this study. The mechanism of NO₃ ⁻ , HCO₃ ⁻ and Fe 3+ accelerating the photodegradation of METH in water was proposed to proceed via the generation of hydroxyl radical (HO∙), leading to the oxidation of METH, along with the involvement of nitro radical (∙NO 2 ) and carbonate radical (CO 3 •- )., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Improving support options for people who use methamphetamine is of critical national and global importance. The role of mutual-help groups within the treatment-seeking journey of people who use methamphetamine is unclear. Self-Management and Recovery Training ('SMART Recovery') mutual-help groups are led by a trained facilitator and support participants to work on individual goals, including, but not limited to abstinence. This study examined how people who use methamphetamine came to be involved in SMART Recovery mutual-help groups and factors associated with engagement., Methods: A sample of Australian SMART Recovery participants who self-reported using methamphetamine in the preceding 12-months (n = 18) discussed their history of substance use and experience of service provision in a semi-structured telephone interview. Interviews were audio-recorded, transcribed, and analysed using iterative categorization., Results: Participant initiation of SMART Recovery groups was described across two themes: i) delayed attendance and ii) use as an adjunct to other services. Factors associated with engagement were discussed in terms of: i) the 'fit' of SMART Recovery mutual-help groups; ii) coping and tolerance of discomfort; iii) the power of shared lived experience; iv) choice and autonomy; and v) short-term goal setting supports self-efficacy and the possibility of change., Discussion and Conclusions: SMART Recovery mutual-help groups show promise for engaging people who use methamphetamine. There is a clear need to improve awareness of mutual-help group options amongst service users, providers and the general community. Offering choice over mutual-help groups may help to engage people earlier and support improved linkage between services., Competing Interests: Declaration of competing interest No financial conflict of interest exists. At the time of the study authors AKB, BL, VM, FPD, ALB, LH, and PJK all volunteered as members of the SMART Recovery Australia Research Advisory Committee and AA was employed by SMART Recovery Australia as the National Program Manager and Trainer., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Methamphetamine (METH) consumption is associated with aggression. Decoction derived from the kratom ( Mitragyna speciosa Korth.) leaf has been used as a METH substitute in Southeast Asia. Given its perceived benefit, we investigated the relationship between kratom use and aggression in a treatment sample of METH users with and without kratom use history. Four hundred and three male METH users participated in this cross-sectional study. A semi-structured questionnaire and several objective clinical measures were administered. Results indicate that there were no significant differences in aggression and its dimensions between METH users with and without kratom use history. However, two distinct Clusters (1 and 2) of METH users with kratom use history were studied. Users in Cluster 1 were characterized by a higher quantity and frequency of daily kratom use, longer duration of kratom use, and use of kratom at a younger age. Users in Cluster 2 exhibited the opposite characteristics. Kratom dependence and the first age of kratom use were identified as risk factors for aggression in Cluster 1. The frequency of daily kratom use appeared as a protective factor against aggression in Cluster 2. The results offer partial support to the instrumental kratom use concept; lower frequency (1 to 3 times) of kratom use may potentially minimize aggression in METH users presenting with mild to moderate kratom dependence.

Methamphetamine, pseudoephedrine, and related drugs are among the first drugs used for the stimulation of the central nervous system. In this study, two adsorbents based on graphene oxide (GO) were synthesized and used for the analysis of methamphetamine and pseudoephedrine. The prepared nano-adsorbents based on GO in this study were coated by polyaniline (PANI) and Fe 3 O 4 /C-nanodot/GO (magnetic adsorbent). The average size of nanoparticles (GO/PANI) was 18.43 nm. The specific surface area and pore size diameter of Fe 3 O 4 /C-nanodot/GO were 22.71 m 2 g - 1 and 15.23 nm, respectively. Experimental variables affecting the extraction efficiency of the analytes such as pH of the sample solution, amount of adsorbent, extraction time, and type of eluents were investigated and optimized by response surface methodology. Under optimum conditions, GO/PANI and Fe 3 O 4 /C-nanodot/GO were considered appropriate solid phase extraction adsorbents for HPLC-based analyses of the studied drugs in human urine samples. However, GO/Fe 3 O 4 nano adsorbent (Fe 3 O 4 /C-nanodot/GO) showed superior working condition than GO/PANI. The validated proposed analytical methods can be used for the quantitative determination of methamphetamine and pseudoephedrine in actual samples., (© 2024. The Author(s).)

Background: The substitution of cannabis for alcohol and other drugs has been conceptualised in a harm reduction framework as where cannabis is used to reduce the negative side-effects, addiction potential, and social stigma of other drugs. There is currently mixed evidence with recent reviews suggesting cannabis co-use patterns may vary by age and ethnicity. Yet few studies have had large enough samples to examine this demographic variation in detail., Aims: To explore the co-use of cannabis with alcohol and other drugs within demographic subgroups of a large sample of people who use cannabis. Specifically: (1) whether cannabis is being substituted for other drugs, and (2), whether cannabis use leads to more, less or the same level of other drug use., Method: Online convenience survey promoted via Facebook™ completed by 23,500 New Zealand respondents. Those who had used cannabis and any of eight other substances in the same six-month period were asked if their use of cannabis had any impact on their use of each other substance ("a lot more", "little more", "no impact/same", "little less", "a lot less"). Frequency and quantity used of each other drug was compared by co-use group. Generalised logistic regression models were developed to predict co-use categories., Results: Significant proportions reported cannabis use led to "less" alcohol (60%), synthetic cannabinoid (60%), morphine (44%) and methamphetamine (40%) use. Those who reported using "less" had lower frequency and amount used of other drugs. Approximately seven-out-ten reported cannabis use had "no impact" on LSD, MDMA, and cocaine use. One-in-five reported using cannabis led to "more" tobacco use. Young adults (21-35-years) were more likely to report cannabis use led to "less" drinking and methamphetamine use. Adolescent co-users (16-20 years) reported mixed impacts. Māori were more likely to report cannabis use resulted in "less" alcohol, tobacco, methamphetamine, and LSD use. Students and those living in cities were less likely to report cannabis use lowering use of other substances., Conclusion: Cannabis and other drug co-use patterns are moderated by life stages, lifestyles, cultural perspectives, and urbanicity. Harm reduction initiatives and policy reforms should take account of these moderating factors., (© 2024. The Author(s).)

Nan Bao detox capsule (NBDC), derived from ancient Chinese opioid detox protocols, shows promising therapeutic potential in substance abuse disorders, particularly for attenuating methamphetamine (MA) addiction. This study aimed to identify active ingredients, evaluate therapeutic efficacy in an MA addiction rat model and delineate pharmacodynamic mechanisms using metabolomics. In vitro phytochemical profiling characterized 258 drug-related compounds, with 87 prototype entities mainly identified in rat plasma. NBDC significantly attenuated METH-induced behavioural anomalies and modulated neurotransmitter levels, notably increasing brain DA and serotonin (5-HT) content with concomitant upregulation of D1 dopamine receptor (DRD1) and 5-HT1A receptor (5-HT1AR) expression, ameliorating hippocampal pathology. Metabolomic analysis identified histamine receptor as a potential target and revealed the involvement of NBDC in metabolic pathways associated with cocaine addiction, amphetamine abuse and Parkinson's disease. Conclusively, NBDC presents a promising therapeutic agent for mitigating MA addiction through a synergistic interplay of multiple constituents, pharmacological targets and metabolic pathways., (© 2024 The Author(s). Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Addiction can be viewed as a state of compulsive engagement in drug use. It is believed that drug-associated memories maintain compulsive drug-seeking behavior. Therefore, disrupting drug-associated memories may reduce drug-seeking behavior. In the present study, a conditioned place preference (CPP) apparatus was conducted to evaluate the effect of cannabinoid receptor type 1 (CB1R) agonist and antagonist on the acquisition of CPP induced by methamphetamine (METH). Anxiety behaviors and memory retrieval were assessed using elevated plus maze (EPM) and step-through passive avoidance tasks. In this study using a 5-day schedule of CPP, exposure to METH increased the time spent in the drug-paired compartment, and CB1Rs agonist (WIN 55,212-2, WIN) disrupted the METH-induced CPP. In the EPM experiment, METH significantly decreased the ratio of times spent in the open arms to total times spent in any arms (OAT) and the ratio of entries into open arms to total entries (OAE), indicating that METH increases anxiety-like behaviors. However, the CB1Rs antagonist (SR141716A, SR) reversed METH-induced anxiety behaviors. The results obtained in the passive avoidance experiment showed that blockade of brain CB1Rs by SR improves METH-induced amnesia. In summary, CB1Rs appear to modulate METH-associated memories, and antagonists of CB1Rs may serve as a therapeutic target for METH-induced anxiety behaviors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Methamphetamine (METH) is a highly addictive and widely abused drug that causes complex adaptive changes in the brain's reward system, such as the nucleus accumbens (NAc). LASP1 (LIM and SH 3 domain protein 1) as an actin-binding protein, regulates synaptic plasticity. However, the role and mechanism by which NAc LASP1 contributes to METH addiction remains unclear. In this study, adult male C57BL/6J mice underwent repeated METH exposure or METH-induced conditioned place preference (CPP). Western blotting and immunohistochemistry were used to determine LASP1 expression in the NAc. Furthermore, LASP1 knockdown or overexpression using adeno-associated virus (AAV) administration via stereotactic injection into the NAc was used to observe the corresponding effects on CPP. We found that repeated METH exposure and METH-induced CPP upregulated LASP1 expression in the NAc. LASP1 silencing in the NAc reversed METH-induced CPP and reduced PSD95, NR2A, and NR2B expression, whereas LASP1 overexpression in the NAc enhanced CPP acquisition, accompanied by increased PSD95, NR2A, and NR2B expression. Our findings demonstrate an important role of NAc LASP1 in modulating METH induced drug-seeking behavior and the underlying mechanism may be related to regulate the expression of synapse-associated proteins in the NAc. These results reveal a novel molecular regulator of the actions of METH on the NAc and provide a new strategy for treating METH addiction., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Methamphetamine (MA) use disorder is a chronic neurotoxic brain disease characterized by a high risk of relapse driven by intense cravings. However, the neurobiological signatures of cravings remain unclear, limiting the effectiveness of various treatment methods. Diffusion MRI (dMRI) scans from 62 MA users and 57 healthy controls (HC) were used in this study. The MA users were longitudinally followed up during their period of long-term abstinence (duration of long-term abstinence: 347.52±99.25 days). We systematically quantified the control ability of each brain region for craving-associated state transitions using network control theory from a causal perspective. Craving-associated structural alterations (CSA) were investigated through multivariate group comparisons and biological relevance analysis. The neural mechanisms underlying CSA were elucidated using transcriptomic and neurochemical analyses. We observed that long-term abstinence-induced structural alterations significantly influenced the state transition energy involved in the cognitive control response to external information, which correlated with changes in craving scores (r ∼ 0.35, P <0.01). Our causal network analysis further supported the crucial role of the prefrontal cortex (PFC) in craving mechanisms. Notably, while the PFC is central to the craving, the CSAs were distributed widely across multiple brain regions (P FDR <0.05), with strong alterations in somatomotor regions (P FDR <0.05) and moderate alterations in high-level association networks (P FDR <0.05). Additionally, transcriptomic, chemical compounds, cell-type analyses, and molecular imaging collectively highlight the influence of neuro-immune communication on human craving modulation. Our results offer an integrative, multi-scale perspective on unraveling the neural underpinnings of craving and suggest that neuro-immune signaling may be a promising target for future human addiction therapeutics., Competing Interests: Declaration of competing interest The authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: 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., Methods: 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., Findings: 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., Discussion and Conclusions: 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., (© 2024 Australasian Professional Society on Alcohol and other Drugs.)

Methamphetamine (METH) substance use disorder is a long-standing and ever-growing public health concern. Efforts to develop successful immunotherapies are ongoing with vaccines that generate strong antibody responses are an area of significant research interest. Herein, we describe the development of a METH Hapten conjugate vaccine comprised of either two short-length peptides as linkers and mannan as an immunogenic delivery carrier. Initially, Hapten 1 (with a monoamine linker) and Hapten 2 (with a diamine linker) were synthesised. Each step of the Hapten synthesis were characterized by LC-MS and purified by Flash Chromatography and the identity of the purified Haptens were confirmed by 1 H NMR. Haptens were conjugated with mannan (a polymannose), and conjugation efficiency was confirmed by LC-MS, TLC, 1 H NMR, and 2,4 DNPH tests. The immunogenic potential of the two conjugated vaccines were assessed in mice with a 3-dose regimen. Concentrations of anti-METH antibodies were measured by enzyme-linked immunosorbent assay. All the analytical techniques confirmed the identity of Hapten 1 and 2 during the synthetic phase. Similarly, all the analytical approaches confirmed the conjugation between the Haptens and mannan. Mouse immunogenicity studies confirmed that both vaccine candidates were immunogenic and the vaccine with the monoamine linker plus adjuvants induced the highest antibody response after the second booster., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 (GABA A R) 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 GABA A R 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., (© 2024. The Author(s).)

Objectives: Addressing the methamphetamine epidemic will require a more complete understanding of its effect on healthcare systems and of the populations at risk. The objective of the study was to assess the impact of methamphetamine use on psychiatric emergency services outcomes and on Asian American (AA) and Pacific Islander (PI) populations, a historically overlooked population in substance use research., Methods: A retrospective chart review was performed for all visits to a large level I trauma center in urban Hawaii from 2007 to 2019 that required psychiatric emergency services and in which urine drug screening was completed (N = 44,658). Demographic characteristics and emergency room courses were compared between amphetamine-positive and amphetamine-negative visits., Results: The proportion of amphetamine-positive visits approximately doubled from 13.3% in 2007 to 25.5% in 2019. Amphetamine-positive visits were more likely to involve arrival by law enforcement (38.3% vs 27.2.%, P < 0.001), require intramuscular psychotropic medications (17.3% vs 12.3%, P < 0.001), and have longer emergency department lengths of stay (median, 420 vs 372 minutes, P < 0.001). Visits by Native Hawaiian and Hispanic/Latino patients had the highest rate of amphetamine positivity, while visits by Chinese and Korean patients had the lowest., Conclusions: The findings reveal a concerning rise in amphetamine positivity that is associated with increased resource utilization. There was also significant variability in the rate of amphetamine positivity within the AA and PI population, a group of ethnicities often analyzed as a single entity in previous studies. Culturally sensitive interventions may curb the methamphetamine epidemic's effect on healthcare systems and vulnerable populations., Competing Interests: Conflicts of Interest and Source of Funding: For all authors, none were declared., (Copyright © 2024 American Society of Addiction Medicine.)

Introduction: Barriers to help-seeking for illicit drug use cross psychosocial (e.g., knowledge of where to seek help, attitudinal beliefs like being afraid of what people will think) and structural (e.g., service availability) domains. Along with people who use illicit drugs, it is important to consider the perspectives of other key groups who are often involved in the help-seeking and recovery process. This study aimed to examine the perceived barriers to help-seeking for people who use crystal methamphetamine ('ice') among key groups (people who use crystal methamphetamine, families and friends, health workers) as well as the general community., Methods: A cross-sectional online survey open to all Australian residents (aged ≥18 years) was conducted November 2018-March 2019. Four key groups of interest were recruited to examine and compare perceived barriers to help-seeking for crystal methamphetamine use., Results: Participants (n = 2108) included: people who use/have used crystal methamphetamine (n = 564, 39%), health workers (n = 288, 26.8%), affected family/friends (n = 434, 13.7%) and general community (n = 822, 20.6%). People who used crystal methamphetamine demonstrated increased odds of reporting attitudinal (OR 1.35; 1.02-1.80) or structural (OR 1.89; 1.09-3.27) barriers, or a previous negative help-seeking experience (OR 2.27; 1.41-3.66) compared to knowledge barriers. Health workers demonstrated decreased odds of reporting attitudinal compared to knowledge barriers (OR 0.69; 0.50-0.95)., Discussion and Conclusions: Perceived barriers to seeking help for crystal methamphetamine use differed among key groups involved in treatment and recovery. Acknowledging and addressing the mismatches between key groups, through targeted interventions may better support people to seek help for crystal methamphetamine use., (© 2024 The Author(s). Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Purpose: Negative emotions can cause people to make irrational decisions, and decision-making disorders may lead individuals who use methamphetamine (meth) to relapse. Therefore, the current study was performed to investigate whether emotion regulation (ER) can improve negative emotions and thus improve decision-making behavior of individuals who use meth., Method: Based on the Iowa Gambling Task, a three-factor mixed experimental design was used to examine the effects of cognitive reappraisal and expressive suppression strategies on negative emotions and decision-making behaviors of 157 individuals who use meth., Results: Cognitive reappraisal and expressive suppression were effective in reducing participants' negative emotions and improving decision-making behaviors. Specifically, two types of ER strategies were effective in improving decision-making abilities of participants with negative emotional distress, and cognitive reappraisal was more effective than expressive suppression., Conclusion: Regarding cognitive reappraisal, female participants showed better decision-making behavior than males, which predicts that females who use meth might be more adept at using cognitive reappraisal. This finding suggests that mental health providers should aid substance users in managing their negative emotions and also pay attention to gender differences during the nursing process. [ Journal of Psychosocial Nursing and Mental Health Services, 62 (11), 27-34.].

Introduction: There has been a significant increase in methamphetamine/amphetamine use in North America, particularly among people who use opioids. Despite its association with several negative health consequences, the population of people who use methamphetamine/amphetamine with opioids is not well characterised. The aim of this study was to investigate correlates of methamphetamine/amphetamine use among adults with prescription-type opioid use disorder (POUD) starting methadone or buprenorphine/naloxone as part of a pragmatic randomised treatment trial in Canada., Methods: Multivariable logistic regression analyses were used to determine factors associated with baseline methamphetamine/amphetamine use (measured by urine drug test [UDT]) among participants of a pan-Canadian pragmatic trial conducted between 2017 and 2020 comparing supervised methadone versus flexible take-home dosing buprenorphine/naloxone models of care in people with POUD (e.g., licit or illicit, including fentanyl, prescribed or not)., Results: The sample included 269 participants, of which 142 (52.8%) had positive baseline methamphetamine/amphetamine UDT. In the multivariable model, positive fentanyl UDT (adjusted odds ratio [AOR] 13.21, 95% confidence interval [CI] 6.45, 28.30), non-fatal overdose in the last 6 months (AOR 2.26, CI 1.01, 5.17) and a lifetime history of opioid agonist therapy exposure prior to study entry (AOR 2.30, CI 1.09, 4.87) remained positively associated with baseline methamphetamine/amphetamine use., Discussion and Conclusions: In this sample of people with POUD, methamphetamine/amphetamine use was associated with markers of complex and severe OUD, including overdose risk. This suggests the need for targeted interventions to optimise treatment outcomes and prevent future overdoses in this population., Clinical Trial Registration: Available at: ClinicalTrials.gov NCT03033732., (© 2024 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

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&#95;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., (© 2024. The Author(s).)

Objectives: The primary focus of this study is to determine if rural methamphetamine positive patients experience longer hospital length of stays compared to urban methamphetamine positive patients following an orthopaedic trauma., Methods: Patients presenting with traumatic orthopaedic injuries and urine drug screen were categorized into urban, suburban, and rural cohorts found in the Rural Urban Commuting Area codes based on home residence zip codes. Demographic, injury, hospital stay, and follow-up data were collected from the medical records. Comparisons between cohorts were determined by Chi square, Fisher exact, unpaired t-Tests, or ranked sum tests., Design: A retrospective cohort analysis., Setting: Academic Level I Trauma Center., Patient Selection Criteria: Patient records were examined between January 2013 to January 2023 for a traumatic orthopaedic injury and a urine drug screen result at the time of presentation to an academic Level I trauma center., Outcome Measures and Comparisons: Methamphetamine use status, patient age at time of admission, sex, marital status, insurance status, home zip code, orthopaedic injury location, complications, if the patient underwent surgery for orthopaedic injuries, admission date, discharge date, and discharge location were measured., Results: 249 patients met inclusion criteria for this analysis. Methamphetamine positive patients are significantly more likely to be younger, more likely to have surgery for orthopaedic injuries, experience a medical complication, or be discharged to home or a rehabilitation facility compared to methamphetamine negative patients. Urban patients experienced a shorter length of stay compared to suburban and rural patients, regardless of methamphetamine use status. Patients with Medicare, military, workers compensation, or commercial insurance are significantly more likely to attend follow-up appointments than patients with Medicaid or self-pay., Conclusions: Methamphetamine positive patients overall do not experience a longer length of hospital stay compared to methamphetamine negative patients. Rural methamphetamine positive patients experience a longer length of hospital stay compared to urban methamphetamine positive patients., Competing Interests: Declaration of competing interest The author group has the following disclosures: Ashwin R. Garlapaty: Nothing to disclose Anna N. Sullentrup: Nothing to disclose Terrell Christian: Nothing to disclose Kylee Rucinski: Nothing to disclose Brett D. Crist: Has the following disclosures: • AO Trauma North America: Board or committee member • Arthrex, Inc.: Other financial or material support • Curvafix: Paid consultant; paid presenter or speaker • DePuy, A Johnson & Johnson Company: Paid presenter or speaker • Fragility Fracture Network-USA: Board or committee member • Globus Medical: IP royalties • International Geriatric Fracture Society: Board or committee member • Journal of Hip Preservation: Editorial or governing board • Journal of Orthopaedic Trauma: Editorial or governing board • Kinetic Concepts, Inc.: Paid consultant; paid presenter or speaker • Orthocentric: Unpaid consultant • Orthopaedic Trauma Association: Board or committee member • RomTech: Stock or stock options • SLACK Incorporated: Editorial or governing board • Synthes: Paid consultant; research support • Urgo Medical: Unpaid consultant, (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: Methamphetamine addiction is a serious and difficult-to-treat disorder. Existing treatment options are limited, and patient perspectives on effective strategies are lacking. Emergency departments (EDs) may be a critical entry point for individuals with methamphetamine use disorder (MUD) to be identified and linked to treatment. We aimed to understand patients' perspectives regarding their methamphetamine use and related ED experiences and how to improve linkage to substance treatment., Methods: Between July and November 2022, semistructured qualitative interviews were conducted with adult patients with MUD in an urban safety-net healthcare setting in Denver, Colorado. Interviews were recorded, summarized, and analyzed using the Rapid Assessment Process., Results: During the interviews, 18 patients shared their experiences. Participants described feeling stigmatized and experiencing a lack of communication from ED staff during their visit. Additionally, participants shared the perception that ED staff often did not take their health concerns seriously once substance use was identified. Participants were uncertain about overdose risk and felt that their psychiatric symptoms complicated treatment. Referrals to treatment were lacking, and participants supported a care navigation intervention that incorporates elements of contingency management. Participants also shared the importance of ED staff recognizing their social needs and being empathetic, trauma-informed, and flexible to meet patients where they are regardless of their readiness to seek treatment., Conclusions: Treatment options and entry points for individuals with MUD are currently limited. The patient perspectives described here are helpful in developing services to support, engage, and link individuals to MUD services after discharge from ED services., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 American Society of Addiction Medicine.)

Introduction: Helplines are often the first contact with the alcohol and other drug (AOD) treatment system. We examined call data from an AOD helpline in Victoria, Australia, to explore the association between COVID-19 lockdown measures and frequency of calls., Methods: This was a retrospective analysis of AOD helpline data collected between January 2018 and September 2020, for alcohol, methamphetamine and cannabis use concerns. Linear and logistic regression analyses examined differences in pre-COVID-19 (January 2018 to March 2020) and during COVID-19 (March 2020 to September 2020) caller characteristics, and interrupted time-series analyses examined changes in frequency of calls relative to lockdown measures., Results: There were 14,340 calls for alcohol (n = 10,196, 71.10%), methamphetamine (n = 2522, 17.59%) and cannabis (n = 1622, 11.31%). Relative to pre-COVID-19, during COVID-19 there was an increase in the rate of change over time in number of alcohol calls (b = 0.39), increase in first-time alcohol callers (OR = 1.29), and reduction in first-time methamphetamine callers (OR = 0.80). During COVID-19, alcohol callers had lower Socio-Economic Indicators for Areas scores (b = -3.06) and cannabis callers were younger (b = -2.07). During COVID-19, there were reductions in alcohol calls involving counselling/support (OR = 0.87) and information provision (OR = 0.87), cannabis calls involving information provision (OR = 0.71) and methamphetamine calls involving referral (OR = 0.80)., Discussion and Conclusions: In the first 6 months of the pandemic, frequency of alcohol-related calls increased over time, and first-time alcohol-related callers increased. The number of calls for cannabis and methamphetamine remained stable. Results suggest the helpline was not used to its full capacity, suggesting a role for further promotion during times of crises., (© 2024 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Methamphetamine (METH), an abused psychostimulant, impairs cognition through prolonged or even single-dose exposure, but animal experiments have shown contradictory effects on memory deficits. In this study we investigated the effects and underlying mechanisms of single-dose METH administration on the retrieval of object recognition memory (ORM) in mice. We showed that single-dose METH administration (2 mg/kg, i.p.) significantly impaired ORM retrieval in mice. Fiber photometry recording in METH-treated mice revealed that the activity of prelimbic cortex glutamatergic neurons (PrL Glu ) was significantly reduced during ORM retrieval. Chemogenetic activation of PrL Glu or glutamatergic projections from ventral CA1 to PrL (vCA1 Glu -PrL) rescued ORM retrieval impairment. Fiber photometry recording revealed that dopamine (DA) levels in PrL of METH-treated mice were significantly increased, and micro-infusion of the D2 receptor (D2R) antagonist sulpiride (0.25 μg/side) into PrL rescued ORM retrieval impairment. Whole-cell recordings in brain slices containing the PrL revealed that PrL Glu intrinsic excitability and basal glutamatergic synaptic transmission were significantly reduced in METH-treated mice, and the decrease in intrinsic excitability was reversed by micro-infusion of Sulpiride into PrL in METH-treated mice. Thus, the impaired ORM retrieval caused by single-dose METH administration may be attributed to reduced PrL Glu activity, possibly due to excessive DA activity on D2R. Selective activation of PrL Glu or vCA1 Glu -PrL may serve as a potential therapeutic strategy for METH-induced cognitive dysfunction., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background and Aims: Early-life adversities are known to alter drug reward processing in rodents. Despite the well-known link between early adversity and the risk of substance use disorder, few studies have measured how childhood adversity affects human drug reward. Here, we assessed the relationship between historical childhood adversities and responses to single doses of methamphetamine, d-amphetamine or buprenorphine in healthy participants., Methods: Using a secondary analysis approach, we assessed the impact of childhood adversity on drug effects from three randomised, placebo-controlled studies in which healthy volunteers received methamphetamine (20 mg oral; n  = 35), d-amphetamine (20 mg oral; n  = 54) or buprenorphine (0.2 mg sublingual; n  = 35). Ratings of feeling effect, liking, disliking, feeling high and wanting more of the drug were collected 15-210 min post-administration, and heart rate changes were analysed using random-intercept mixed-effect models. The area under the curve from these and previous studies was calculated to visualise the relationship between childhood adversity severity and drug effects., Results: Greater childhood adversity was associated with reduced feel effects (significant three-way interactions b  = -0.07, 95% CI [-0.12, -0.02], p  = 0.009), like effects ( b  = -0.07, 95% CI [-0.13, -0.00], p  = 0.038) and feel high ( b  = -0.06, 95% CI [-0.10, -0.01], p  = 0.020) towards the stimulant drugs 90-180 min post-administration., Conclusions: Childhood adversity was not significantly associated with other subjective or heart rate responses to the drugs. Overall, participants with more childhood adversities reported dampened subjective responses to stimulant drugs, but not to buprenorphine. Future studies should examine the generalisability of these relationships, to identify the mechanisms underlying the link between childhood adversity and drug responsiveness., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research authorship, and/or publication of this article: HDW is on the Board of Directors of PharmAla Biotech and consultant to Awakn Life Sciences and Gilgamesh Pharmaceuticals. These were unrelated to the present research. No other conflicts to declare.

Introduction: Amphetamine-type stimulants (ATSs) are related to significant harm worldwide, with limited effective pharmacological treatments for ATS use disorder (ATSUD). Modafinil has been explored as a potential treatment for ATSUD. This systematic review and meta-analysis (PROSPERO ID: CRD42023388487) aimed to evaluate the efficacy and safety of modafinil for the treatment of ATSUD., Methods: A comprehensive search of major indexing sources and trial registries, from inception to search date, was conducted on February 15, 2023, and updated on October 31, 2023. Eligible studies were randomized placebo-controlled trials (RCTs) of modafinil in individuals meeting the criteria for the Diagnostic and Statistical Manual of Mental Disorders, fourth and fifth editions, diagnoses of ATSUD. Eligible studies were assessed for risk of bias, using the Cochrane Risk of Bias tool. The primary outcome included the effect of modafinil on ATS use. Secondary outcomes included retention in treatment, ATS craving, treatment discontinuation due to adverse events (AEs), and serious AEs. Subgroup analysis by modafinil dose was conducted where appropriate. Risk ratio (RR) or Peto's odds ratio (OR) was calculated for the meta-analysis of dichotomous variables and standardized mean difference (SMD) was calculated for the random-effect meta-analysis of continuous variables., Results: Five RCTs ( N  = 451 participants) were included. Modafinil did not significantly impact ATS use (RR = 0.99; 95% CI, 0.97 to 1.02; p  = 0.655), retention in treatment (RR = 1.02; 95% CI, 0.91 to 1.14; p  = 0.799), ATS craving (SMD = -0.36; 95% CI, -1.19 to 0.47; p  = 0.398), or treatment discontinuation due to AEs (Peto's OR = 0.48; 95% CI, 0.20 to 1.14; p  = 0.100). These results were consistent across subgroup analyses. More episodes of serious AEs were reported in the modafinil group than in the placebo group, at higher doses (Peto's OR = 4.80; 95% CI, 1.18 to 19.56, p  = 0.029)., Conclusion: There is currently no evidence suggesting that modafinil has a statistically significant effect on efficacy outcomes in populations with ATSUD. Continued research into effective treatments and harm reduction strategies for ATSUD is essential., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: LE is a shareholder and employee of OneCare Inc., which is a biotechnology mental health company. OneCare Inc., biotechnologies’ work does not relate to the contents of the present article. DJA received study materials from Cardiol Therapeutics and Exka for clinical trials not related to the present article (2022–2024). The other authors have no potential conflicts to declare.

Introduction: To guide improvements in treatment for pregnant persons with substance use disorders within the criminal legal system, treatment programs must first determine the primary substances of concern for this population. The objective of this study is to compare trends in specific substance use upon admission to treatment in pregnancy, based upon whether referrals originated from the criminal legal system or from another referral source., Methods: This research accessed data on perinatal substance use (1995-2021) and referral sources from the Treatment Episode Data Set-Admissions (TEDS-A). Analyses use multiple logistic regressions to evaluate trends in primary substance use leading to treatment admission during pregnancy., Results: Approximately 1 % (N = 536,948) of all substance use treatment admissions in TEDS-A were for pregnant people. Between 1995 and 2021, the percentage of treatment admissions increased for primary methamphetamine use (10 % to 27 %), primary opioid use (21 % to 38 %), and primary cannabis use (9 % to 18 %), and decreased for primary cocaine use (32 % to 6 %) and primary alcohol use (26 % to 11 %). By 2021, treatment admissions referred from criminal legal agencies were more likely to primarily be for primary methamphetamine use (33 % vs 25 %) and less likely to be for primary opioid use (22 % vs 42 %) compared to other referral sources., Conclusions: Trends in substance use treatment during pregnancy have changed substantially over the past few decades and emphasize the unique needs of patients referred to treatment by the criminal legal system. Treatment programs must therefore adapt to fluctuating trends in perinatal substance use. In particular, it is important to expand programs that prioritize treatment of methamphetamine use disorder for pregnant people referred through criminal legal agencies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Sexual minority men are disproportionately affected by methamphetamine use, with recent studies suggesting an increase in use specifically among Black sexual minority men. Black sexual minority men face unique structural barriers to achieving optimal health. Given its harmful effects, and in light of existing health disparities, an increase in methamphetamine use among Black sexual minority men poses a significant public health concern., Objective: The Health Impacts and Struggles to Overcome the Racial Discrimination of Yesterday (HISTORY) study is investigating the potential impacts of exposure to the census tract-level structural racism and discrimination (SRD) on methamphetamine use among Black sexual minority men in Atlanta, Georgia, and will identify intervention targets to improve prevention and treatment of methamphetamine use in this population., Methods: This study uses a mixed methods and multilevel design over a 5-year period and incorporates participatory approaches. Individual-level quantitative data will be collected from a community-based cohort of Black sexual minority men (N=300) via periodic assessment surveys, ecological momentary assessments, and medical record abstractions. Census tract-level measures of SRD will be constructed using publicly available administrative data. Qualitative data collection will include longitudinal, repeated in-depth interviews with a subset (n=40) of study participants. Finally, using a participatory group model-building process, we will build on our qualitative and quantitative data to generate causal maps of SRD and methamphetamine use among Black sexual minority men, which in turn will be translated into actionable recommendations for structural intervention., Results: Enrollment in the HISTORY study commenced in March 2023 and is anticipated to be completed by November 2024., Conclusions: The HISTORY study will serve as a crucial background upon which future structural interventions can be built, to mitigate the effects of methamphetamine use and SRD among Black sexual minority men., International Registered Report Identifier (irrid): DERR1-10.2196/63761., (©Samuel C O Opara, Sabriya L Linton, Brian W Weir, Natalie D Crawford, David P Holland, Antonio Newman Jr, McKinsey Bullock, Marcus O Reed, Srija Dutta, Kamini Doraivelu, Charles Stephens, Justin C Smith, Yeeli Mui, Sophia A Hussen. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 31.10.2024.)

Introduction: This study explored the effects of task-switching type and sex on the task-switching ability of methamphetamine abstainers, as well as the differences in brain mechanisms under drug cravings under drug cravings using near-infrared spectroscopy., Methods: Craving-inducing videos were used to arouse 20 methamphetamine abstainers (including 10 men), whose switching ability was then assessed using voluntary and cued task-switching exercises., Results: During task-switching under methamphetamine cravings, the activation of the premotor cortex (PMC), supplementary motor area (SMA), frontal eye field (FEF), and dorsolateral prefrontal cortex (DLPFC) in women was significantly stronger than in men, while the activation of FEF in men was significantly stronger than in women. Voluntary task-switching induced stronger FEF activation than cued task-switching. During the latter, women exhibited stronger activation in the anterior prefrontal cortex (aPFC) than men., Discussion: Both men and women showed brain lateralization during task-switching under methamphetamine cravings. Men tended to adopt proactive control and use a top-down dominant strategy to start a new task. Women, however, tend to use a bottom-up strategy focusing on inhibiting old tasks and emotional switching. Moreover, in cued task-switching, the result shows women paid more attention to emotional processing than did men, which suggests that different task-switching training programs should be developed according to sex., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jiang, Yang, Huang, Zhao, Li, Chen, Jin and Zhou.)

Background: Pulmonary arterial hypertension (PAH) is a rare, chronic, progressive form of pulmonary hypertension in which increased arterial pressure causes remodeling of the arterial system and is associated with heart failure. Methamphetamine is a stimulant that has recently become a focus in PAH research, but the recent trends and demographics of this cohort of patients are not known. The study aimed to analyze the overall trends and demographics of PAH patients with and without concurrent methamphetamine usage., Methods: The study used the National Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), and Agency for Healthcare Research and Quality (AHRQ) from 2008 to 2020 to calculate nationally weighted estimates for both conditions by ICD-9 and ICD-10 diagnosis codes. We used several statistical measures, including descriptive statistics with design-based chi-square and t -tests, trend analysis with Cochran-Armitage test, generalized linear models, and other data preprocessing measures., Results: A significant increase was evident in patients with pulmonary arterial hypertension (PAH) and concurrent methamphetamine use (9.2-fold). Most of the hospitalized patients were males (59.16%), aged 41-64 (45.77%), White (68.64%), from the West (53.09%), with Medicaid (50.48%), and with median income <$25,000. The rate of increase over the period was higher for males (11.8-fold), race (not sure which race; please check and modify), aged 41-64 (11.3-fold), and in the South (15.1-fold). An overall adjusted prevalence ratio (PR) for PAH hospitalizations among concurrent methamphetamine users was 32.19 (CI = 31.19-33.22) compared to non-users. With respective reference categories, the significantly higher PR was evident for males, patients aged 41-64, White, with Medicare, median income <$25,000, all regions compared to Northeast, length of hospital stays, and conditions, including chronic pulmonary disease, diabetes, hypertension, obesity, and peripheral vascular disorders., Conclusion: This study reveals a national overall and demographic-specific trend of increasing PAH with concurrent methamphetamine usage and associated factors. The findings may help to understand the current patterns and identify the vulnerable sociodemographic cohorts for further research and to take appropriate policy measures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Husein, Boullion, Hossain, Xing, Khan, Bhuiyan, Kolluru, Bhuiyan, Goeders, Conrad, Vanchiere, Orr, Kevil and Bhuiyan.)

GABA B receptors play a modulatory role in the mechanisms underlying drug addiction, sleep problems, and aging; however, there are few studies addressing their relationships to each other. Therefore, this study aimed to examine whether blockade of these receptors affects methamphetamine (METH) reward memory in adult and adolescent rapid-eye movement sleep-deprived (RSD) rats. Adolescent and adult male Wistar rats were subjected to RSD for seven days. They were then conditioned to receive methamphetamine (METH; 2 mg/kg, ip) during an eight-day conditioning period. METH reward memory was then reactivated during a retrieval trial and the GABA B receptor agonist baclofen (2.5 or 5 mg/kg, ip) was injected prior to the retrieval trial. Afterward, animals were retested for the expression of conditioned place preference (CPP) and hippocampal expression of GABA B receptors. Baclofen dose-dependently decreased the retrieval of METH reward memory in control and RSD adult and adolescent rats, but its effects were stronger at the higher dose. Moreover, we found stronger effects of baclofen in adolescent animals than in adult ones. In addition, baclofen at its higher dose decreased GABA B overexpression in the hippocampus of adolescent rats, but not in adult rats. These findings shed new light on the mechanisms underlying the role of GABA B receptors in the retrieval of METH reward memory and highlight the importance of considering age and sleep problems in understanding addiction. Further research could potentially lead to the development of therapeutics for individuals struggling with METH addiction., Competing Interests: Declaration of competing interest The authors have no conflicts to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Substance use is associated with decreased antiretroviral therapy (ART) adherence among people with HIV (PWH). Adherence plays a significant role in mediating the negative effects of substance use on HIV suppression and is a principal modifiable patient-level factor in improving HIV suppression and reducing ART drug resistance. Understanding substance use and ART adherence, particularly with rapidly changing substance use epidemiology and ART regimens, is vital to improving HIV care. Among 10,557 PWH (2010-2021) from 8 academic clinical sites nationally we examined longitudinal associations of substance use severity and number of substances used (measured using AUDIT-C and modified ASSIST) with patient-reported ART adherence (visual analog scale). Alcohol (68% any use, 18% unhealthy use [AUDIT-C > 4 men, > 3 women]), marijuana (33%), and methamphetamine (9%) use were most reported. Polysubstance use was common (32%). Both higher severity substance use and higher number of substances used were associated with lower ART adherence. Severity of methamphetamine use had the strongest dose-response association with ART adherence (low severity [ASSIST 1-3]: -3.05%, 95% CI: -4.23%, -1.87%; moderate [ASSIST 4-26]: -6.20%, 95% CI: -7.08%, -5.33%; high [ASSIST > 26]: -10.77%, 95% CI: -12.76%, -8.78%). Severe substance use, especially methamphetamine, and higher number of illicit drugs used were associated with declines in adherence at levels that were likely clinically meaningful in the modern era of ART. Findings support integrating substance use care with HIV care and potential benefits of harm reduction strategies for improving adherence such as encouraging lower levels of substance use and fewer number of substances used., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Pre-pandemic data suggests that methamphetamine-related mortality and opioid co-involvement have been increasing in the United States (US). However, there was a staggering number of US drug overdose deaths in 2020 and 2021, particularly among males. An updated examination of sex-specific trends in methamphetamine-related mortality, the extent to which these deaths may be driven by the heroin and fentanyl co-involvement, and whether this co-involvement might explain the disproportionate number of male methamphetamine deaths is warranted., Methods: We leveraged final and provisional data from the CDC WONDER multiple causes of death database to examine deaths involving methamphetamine (i.e., psychostimulants with abuse potential, ICD-10 code T43.6) and methamphetamine-related deaths that co-involved heroin and/or synthetic opioids excluding methadone (ICD-10 code T40.4; e.g., fentanyl) among US residents aged 15 - 74 years. We plotted age-adjusted methamphetamine mortality rates by sex and year and quantified the proportion of deaths with heroin/synthetic opioid co-involvement. Finally, we used joinpoint regression models to quantify sex-specific trends in methamphetamine mortality and the proportion of deaths with heroin and/or synthetic opioid co-involvement., Results: From 1999 to 2021, the methamphetamine-related mortality rate increased 58.8-fold among males (0.33 per 100,000 to 19.74 per 100,000) and 65.3-fold among females (0.12 per 100,000 to 7.96 per 100,000), with the greatest increases occurring between 2019 and 2021. The proportion of these deaths that co-involved heroin and/or synthetic opioids increased among both males (13.1% to 61.5%) and females (7.7% to 63.1%) from 1999 to 2021., Conclusions: Increasing methamphetamine-related mortality among males and females has been accompanied by a dramatic increase in the proportion of heroin and/or synthetic opioid co-involvement among both sexes. Robust harm reduction efforts are needed to mitigate these increases, particularly for people who co-use stimulants and opioids., Competing Interests: Declaration of competing interest No financial disclosures have been reported by the authors of this paper., (Copyright © 2024. Published by Elsevier Inc.)

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., (© 2024 Society for the Study of Addiction.)

Background: Individuals with substance use disorder (SUD) are characterized by loss of control in drug use, such as increased impulsivity. Methamphetamine and methcathinone are psychostimulants, the use of which is accompanied by a high level of impulsivity. Whether individuals with methamphetamine use disorder (MUD) and methcathinone use disorder (MCUD) differ in different aspects of impulsivity is unclear., Methods: We investigated impulsivity traits and behaviors in individuals with MUD and MCUD. The Barratt Impulsiveness Scale (BIS), Sensation Seeking Scale (SSS), and delay discounting task (DDT) were assessed in individuals with MUD and MCUD and in healthy controls (HCs); then, we performed network-based analysis and computational modeling to understand the potential differences among the three groups., Results: MUD subjects scored higher than MCUD subjects in terms of motor impulsivity, nonplanning impulsivity, and total BIS scores. The network analysis revealed that there were no significant differences between MUD and MCUD subjects in any centrality indices. The discount rate of MUD and MCUD subjects was significantly greater than that of HCs, whereas there was no difference in the discount rate between the two addiction groups., Conclusions: These findings suggest that MUD and MCUD participants differ in impulsivity traits but not in impulsive behaviors, implying that impulsive traits and behaviors represent different aspects of impulsivity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yin, Cheng, Zhou, Xu, Yang and Yuan.)

The behavioral sensitization, characterized by escalated behavioral responses triggered by recurrent exposure to psychostimulants, involves neurobiological mechanisms that are brain-region and cell-type specific. Enduring neuroadaptive changes have been observed in response to methamphetamine (METH) within the orbitofrontal cortex (OFC), the cell-type specific transcriptional alterations in response to METH sensitization remain understudied. In this study, we utilized Single-nucleus RNA-sequencing (snRNA-seq) to profile the gene expression changes in the OFC of a rat METH sensitization model. The analyses of differentially expressed genes (DEGs) unveiled cell-type specific transcriptional reactions associated with METH sensitization, with the most significant alterations documented in microglial cells. Bioinformatic investigations revealed that distinct functional and signaling pathways enriched in microglia-specific DEGs majorly involved in macroautophagy processes and the activation of N-methyl-D-aspartate ionotropic glutamate receptors (NMDAR). To validate the translational relevance of our findings, we analyzed our snRNA-seq data in conjunction with a transcriptomic study of individuals with opioid use disorder (OUD) and a large-scale Genome-Wide Association Studies (GWAS) from multiple externalizing phenotypes related to drug addiction. The validation analysis confirmed the consistent expression changes of key microglial DEGs in human METH addiction. Moreover, the integration with GWAS data revealed associations between addiction risk genes and the DEGs observed in specific cell types, particularly microglia and excitatory neurons. Our study highlights the importance of cell-type specific transcriptional alterations in the OFC in the context of METH sensitization and their potential translational relevance to human drug addiction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Methamphetamine (METH) is a highly addictive psychostimulant that causes physical and psychological damage and immune system disorder, especially in the liver which contains a significant number of immune cells. Dopamine, a key neurotransmitter in METH addiction and immune regulation, plays a crucial role in this process. Here, we developed a chronic METH administration model and conducted single-cell RNA sequencing (scRNA-seq) to investigate the effect of METH on liver immune cells and the involvement of dopamine receptor D1 (DRD1). Our findings reveal that chronic exposure to METH induces immune cell identity shifts from IFITM3+ macrophage (Mac) and CCL5+ Mac to CD14+ Mac, as well as from FYN+CD4+ T effector (Teff), CD8+ T, and natural killer T (NKT) to FOS+CD4+ T and RORα+ group 2 innate lymphoid cell (ILC2), along with the suppression of multiple functional immune pathways. DRD1 is implicated in regulating certain pathways and identity shifts among the hepatic immune cells. Our results provide valuable insights into the development of targeted therapies to mitigate METH-induced immune impairment., (© The Author(s) 2024. Published by Oxford University Press and Science Press on behalf of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China.)

Drug addiction may result in sleep problems. Importantly, sleep deprivation (SD) is known as an important risk factor for relapse to drug abuse as SD mimics the effects of psychostimulants on dopamine system of the brain. Moreover, aging may affect sleep and drug addiction. This study, therefore, set out to assess the effects of methamphetamine (METH) and REM sleep deprivation (RSD) on locomotor activity, anxiety-like behavior and spatial memory in adult and adolescent rats. Adult and adolescent male Wistar rats received a neurotoxic METH regimen; four subcutaneous injections of 6 mg/kg, at 2 h intervals. Five days later, the animals underwent a 48-h RSD episode using the multiple platforms method. They were then examined using the open field (OF), elevated plus maze (EPM) and Y-maze tasks. We found that the METH and RSD paradigms showed synergistic effects to increase locomotion and risk-taking behavior in both adult and adolescent animals, while only adolescent rats revealed RSD-induced anxiety-like behavior. Moreover, adolescent animals revealed greater sensitization for vertical activity following METH plus RSD episode. In addition, METH and RSD paradigms revealed synergistic effects to impair spatial working memory, but neither METH nor RSD alone affected performance of animals in the Y-maze task. Our findings may indicate that there are important relationships between METH and RSD to induce hyperlocomotion, risk-taking behavior and spatial memory impairment, particularly in adolescent animals. Moreover, it seems that adolescent rats may be more susceptible to anxiety-like behavior and hyperlocomotion than adults., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rationale: The rewarding effect of Methamphetamine (METH) is commonly believed to play an important role in METH use disorder. The altered expression of dopamine D1 receptor (D1R) has been suggested to be essential to the rewarding effect of METH. Notably, D1R could interact with histamine H3 receptors (H3R) by forming a H3R-D1R heteromer (H3R-D1R)., Objectives: This study was designed to specifically investigate the involvement of H3R-D1R in the rewarding effect of METH., Methods: C57BL/6 mice were treated with intraperitoneal injections of a selective H3R antagonist (Thioperamide, THIO; 20 mg/kg), an H1R antagonist (Pyrilamine, PYRI; 10 mg/kg), or microinjections of cytomegalovirus (CMV)-transmembrane domain 5 (TM5) into the nucleus accumbens (NAc). The animal model of Conditioned Place Preference (CPP) was applied to determine the impact of H3R-D1R on the rewarding effect of METH., Results: METH resulted in a significant preference for the drug-associated chamber, in conjunction with increased H3R and decreased D1R expression in both NAc and the ventral tegmental area (VTA). THIO significantly attenuated the rewarding effect of METH, accompanied by decreased H3R and increased D1R expression. In contrast, pyrilamine failed to produce the similar effects. Moreover, the inhibitory effect of THIO on METH-induced CPP was reversed by SKF38393, a D1R agonist. Furthermore, SCH23390, a D1R antagonist, counteracted the ameliorative effect of SKF38393 on THIO. Co-immunoprecipitation (CO-IP) experiments further demonstrated the specific interaction between H3R and D1R in METH CPP mice. The rewarding effect of METH was also significantly blocked by the interruption of CMV-transmembrane domain 5 (TM5), but not CMV-transmembrane domain 7 (TM7) in NAc., Conclusion: These results suggest that modulating the activity of H3R-D1R complex holds promise for regulating METH use disorder and serves as a potential drug target for its treatment., Competing Interests: Declaration of competing interest We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In both preclinical and clinical settings, dysregulated frontostriatal circuits have been identified as the underlying neural substrates of compulsive seeking/taking behaviors manifested in substance use disorders and behavioral addictions including internet gaming disorder (IGD). However, the neurochemical substrates for these disorders remain elusive. The lack of comprehensive cognitive assessments in animal models has hampered our understanding of neural plasticity in addiction from these models. In this study, combining data from a rat model of compulsive taking/seeking and human participants with various levels of IGD severity, we investigated the relationship between regional glutamate (Glu) concentration and addictive behaviors. We found that Glu levels were significantly lower in the prelimbic cortex (PrL) of rats after 20-days of methamphetamine self-administration (SA), compared to controls. Glu concentration after a punishment phase negatively correlated with acute drug-seeking behavior. In addition, changes in Glu levels from a drug naïve state to compulsive drug taking patterns negatively correlated with drug-seeking during both acute and prolonged abstinence. The human data revealed a significant negative correlation between Glu concentration in the dorsal anterior cingulate cortex (dACC), the human PrL counterpart, and symptoms of IGD. Interestingly, there was a positive correlation between Glu levels in the dACC and self-control, as well as mindful awareness. Further analysis revealed that the dACC Glu concentration mediated the relationship between self-control/mindful awareness and IGD symptoms. These results provide convergent evidence for a protective role of dACC/PrL in addiction, suggesting interventions to enhance dACC glutamatergic functions as a potential strategy for addiction prevention and treatment., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

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., (© 2024. The Author(s).)

Methamphetamine use and HIV disproportionately affect sexual and gender minority (SGM) people assigned male at birth. Identifying risk factors for methamphetamine use is crucial to inform preventive interventions. In this cohort study with 1,296 SGM people assigned male at birth, ages 16 to 29, and who resided in Chicago, Poisson regression analyses indicated the prevalence of methamphetamine use increased from 2015 to 2023 [Incidence Rate Ratio (IRR) = 1.07; 95% CI = 1.01 to 1.13; P = 0.02]. This increase was most pronounced among those ages 25 or older at baseline (IRR = 2.20; 95% CI = 1.33 to 3.63; P = 0.002), and 23.9 [Interquartile Range (IQR) = 22.1 to 26.9] was the median age of first-time methamphetamine use. In 826 participants with a prior HIV diagnosis or previous inflammatory measurements, Cox proportional-hazards models examined risk factors for incident, first-time methamphetamine use. Adjusting for other substance use, the rate of incident, first-time methamphetamine use was two-fold greater after HIV diagnosis [adjusted hazard ratio (aHR) = 2.02; 95% CI = 1.27 to 3.23; P = 0.003]. For each SD higher C-reactive protein, the rate of incident, first-time methamphetamine use was 18% greater (aHR = 1.18; 95% CI, 1.05 to 1.34; P = 0.008). HIV seroconversion and inflammation could increase the risk of initiating methamphetamine use in SGM people assigned male at birth., Competing Interests: Competing interests statement:The authors declare no competing interest.

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., (© 2024. The Author(s).)

The pursuit of translational biomarkers is complex due to the heterogeneous human pathophysiology, but critical for disease diagnosis, prognosis, monitoring therapeutic efficacy, and for patient stratification. In HIV-associated neurocognitive impairment (NCI), biomarkers that delineate the trajectory of neuropathogenesis and neurocognitive sequelae are critical, particularly considering confounders such as substance use, including Methamphetamine (METH). METH use is a significant health concern among persons living with HIV (PWH), aggravating cognitive deficits and neuroinflammation despite of antiretrovirals, introducing elements in the microenvironment that are fundamentally differerent in relation to non-METH users, such as high levels of dopamine (DA) affecting HIV-innate immune targets. Yet, current biomarkers do not detect these differences. We hypothesized that predefined DA-induced signatures detectable in peripheral blood leukocytes, can distinguish HIV+ METH users compared to HIV-negative or PWH that are non METH users. The elevated expression of CD8A, CREBBP, CCL5, and combinations of dopaminergic pathway transcripts clustered METH users with detectable CSF viral load and major depressive disorder (MDD), indicating neuroimmune-mechanistic links. Cathecol-o-methyltransferase (COMT) gene polymorphisms affecting DA metabolism improved the identification of PWH using METH with biomarkers. The results indicate that underlying immunedopaminergic mechanisms provide signatures and genotypes that can identify PWH that are METH users and their attributes., Competing Interests: The authors of the manuscript “Identifying Methamphetamine Use Predictors in HIV Infection: Immune-Dopaminergic Signatures in Peripheral Leukocytes and the Role of COMT Genotype” have no conflicts of interest to declare., (© 2024 The Authors.)