Mapping a psychosocial syndemic among methamphetamine-using sexual minority men living with HIV.

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.

The distinct functional brain network and its association with psychotic symptom severity in men with methamphetamine-associated psychosis.

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.

Neuro-Immune Communication at the Core of Craving-Associated Brain Structural Network Reconfiguration in Methamphetamine Users.

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 (PFDR<0.05), with strong alterations in somatomotor regions (PFDR<0.05) and moderate alterations in high-level association networks (PFDR<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.

Impact of HIV-1 tat protein on methamphetamine-induced inhibition of vesicular monoamine transporter2-mediated dopamine transport and methamphetamine conditioned place preference in HIV-1 tat transgenic mice.

Perturbation of dopamine transmission has been implicated as a contributing factor in HIV-1 associated neurocognitive disorders with concurrent methamphetamine (METH) abuse. We have demonstrated that the HIV-1 protein, transactivator of transcription (Tat), decreases dopamine transport through inhibition of vesicular monoamine transporter2 (VMAT2). This study determined the effects of Tat protein on METH-inhibited VMAT2 function and METH-conditioned place preference (CPP). In vitro exposure of isolated mouse whole brain vesicles to recombinant Tat1-86 or METH displayed a concentration-dependent inhibition of the vesicular [3H]Dopamine uptake, in which a combination of Tat and METH induced a greater reduction of dopamine uptake compared to Tat or METH alone. In vivo, the maximal velocity (Vmax) of vesicular [3H]Dopamine uptake was decreased in inducible Tat transgenic (iTat-tg) mice harvested after treatment with either 21-day doxycycline (Dox) or 14-day METH (3 mg/kg, i.p., daily), whereas these mice treated with both Dox and METH displayed an additive reduction of the Vmax compared to either Tat or METH alone. Moreover, Dox-induced Tat expression increased METH-CPP in an exposure-dependent manner, with iTat-tg mice demonstrating a 2.3-fold potentiation of METH-CPP compared with Tat null control mice upon administration of Dox for 14 days. Furthermore, a 7-day administration of Dox reinstated extinguished METH-CPP. Collectively, these results suggest a synergistic effect of Tat protein and METH on inhibition of VMAT2-mediated DA transport, potentially contributing to potentiation of METH-CPP in iTat-tg mice.

Experiences of harm and mental ill-health among gay, bisexual and other men-who-have-sex-with-men who use methamphetamine or GHB/GBL in different combinations: findings from the COMeT study in Taiwan.

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.

Methamphetamine-induced impairment of memory and fleeting neuroinflammation: Profiling mRNA changes in mouse hippocampus following short-term and long-term exposure.

Methamphetamine (METH) has been implicated in inducing memory impairment, but the precise mechanisms underlying this effect remain unclear. Current research often limits itself to singular models or focuses on individual gene or protein functions, which hampers a comprehensive understanding of the underlying mechanisms. In this study, we established three METH mouse exposure models, extracted hippocampal nuclei, and utilized RNA sequencing to analyze changes in mRNA expression profiles. Our results indicate that METH significantly impairs the learning and memory capabilities of mice. Additionally, we observed that METH-induced inflammatory responses occur in the early phase and do not further exacerbate with repeated injections. However, RNA sequencing revealed the persistent enrichment of inflammatory pathway molecules, which correlated with worsened behaviors. This suggests that although METH-induced neuroinflammation plays a critical role in learning and memory impairment, the continued enrichment of inflammatory pathway molecules is associated with behavioral outcomes. These findings provide crucial evidence for the potential application of immune intervention in METH-related disorders.

Methamphetamine abuse impairs sequential working memory.

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. Results 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.

Prevalence of Methamphetamine (Mkpurummiri) use in south east Nigeria: a community-based cross-sectional study.

BACKGROUND: Methamphetamine (MA) (Mkpurummiri) is seen as the most common, accessible and new drug of use/abuse in south east Nigeria. Despite the overwhelming evidence of the dire consequences of this drug to the users, there is lack of empirical research to determine its prevalence in this area where use is assumed to be common. This study aimed to determine the prevalence of MA use, characteristics of the users and the control measures. METHODS: A descriptive cross-sectional survey research design was conducted from May through November 2023 among adolescents/adults at the age bracket of 15-64 years in the five states of south east, Nigeria. Three hundred and seventy-one (371) respondents were recruited using purposive/convenience sampling methods. A semi structured questionnaire was the instrument used. Data were analyzed using percentage, bivariate and multivariate logistics regression statistics. The Prevalence of MA was determined using percentages whereas the factors that are associated with MA use were expressed using multivariate logistics regression statistics AORs and 95%CIs. The level of significance was set at P < 0.05. RESULTS: The prevalence of Methamphetamine (Mkpurummiri) was (21.8%). The most common reason for MA use was depression (86.5%), the most common route of administration was inhalation (64.9%). The most common characteristic of MA (Mkpurummiri) user was aggressive/violent behaviour (94.1%).The control measures were self-control (92.2%), parental monitoring (85.7%), drug education (83.1%) and legal control (80.8%). The multivariate logistics regression statistics AOR shows that off-campus were 3 times (AOR = 0.298; CI = 0.12-0.73 P = 0.008), family house 4 times (AOR = 0.241; CI = 0.09-0.65; P = 0.005 ≤ 0.05 ) less likely than on-campus to predict MA use. Recently married were 3.25 times (aOR = 3.25; CI = 1.47-7.18), divorced 3.45 times (aOR = 3.45; CI = 1.23-9.58), polygamy 2.3 times (aOR = 2.3; CI = 1.08-4.90; P = 0.031 ≤ 0.05 ), tradition 4.44 times (aOR = 4.44; CI = 1.77-11.15; P = 0.001 ≤ 0.05 ) , more likely than others to use MA. CONCLUSIONS: MA use prevalence was relatively high, and marital status, living arrangements, family type and religion were the predictors. These findings underscore the need for concerted effort among the relevant government agencies, community stakeholders, families, religious bodies and school authorities to designing MA use policy/laws with special focus on adopting the punitive measure used in checking cocaine users. This may help to arrest and prosecute the manufacturers, distributors and users of MA.

Cross sectional analysis of an addiction consultation service, substance co-use patterns, and receipt of medications for opioid use disorder during hospitalization.

INTRODUCTION: Despite effective medications for opioid use disorder (MOUD), treatment engagement remains low. As the overdose crisis is increasingly characterized by opioids co-used with other substances, it is important to understand whether existing models effectively support treatment for patients who use multiple substances. Hospital-based addiction consultation services (ACS) have shown promise at increasing MOUD initiation and treatment engagement, but the effectiveness for patients with specific co-use patterns remains unknown. METHODS: Using 2016-2023 admissions data from a large safety net hospital, we estimated a random-effects logistic regression model to determine whether specific co-use (methamphetamine, cocaine, alcohol, sedative, and other) moderated the effect of being seen by ACS on the receipt of MOUD. Adjusting for patient sociodemographic, health, and admission characteristics we estimated the proportion of patients who received MOUD across specific co-use groups. RESULTS: Of 7679 total admissions indicating opioid use, of which 5266 (68.6 %) indicated co-use of one or more substances and 2387 (31.1 %) were seen by the ACS. Among admissions not seen by the ACS, a smaller proportion of admissions with any co-use received MOUD (23.5 %; 95 % CI: 21.9-25.1) compared to admissions with opioid use alone (34.0 %; 95 % CI: 31.9-36.1). However, among admissions seen by the ACS a similar proportion of admissions with any co-use received MOUD (57.8 %; 95 % CI: 55.5-60.1) as admissions with opioid use alone (56.2 %; 95 % CI: 52.2-60.2). The increase in proportion of admissions receiving MOUD associated with being seen by the ACS was larger for admissions with methamphetamine (38.6 percentage points; 95 % CI: 34.6-42.6) or cannabis co-use (39.0 percentage points; 95 % CI: 32.9-45.1) compared to admissions without methamphetamine (25.7 percentage points; 95 % CI: 22.2-29.2) or cannabis co-use (29.1 percentage points; 95 % CI: 26.1-32.1). CONCLUSIONS: The ACS is an effective hospital-based treatment model for increasing the proportion of admissions which receive MOUD. This study shows that ACSs are also able to support increased receipt of MOUD for patients who use other substances in addition to opioids. Future research is needed to further understand what transition strategies best support treatment linkage for patients who use multiple substances.

Decreased consumption of natural rewards in rhesus monkeys with prolonged methamphetamine abstinence.

Rationale: Relapse to drug use is a major clinical challenge in the treatment of addictive disorders, including psychostimulant use and may be exacerbated by reduced sensitivity to natural, non-drug reward. Given the relatively limited set of outcomes, and short withdrawal time in rodent studies, we conducted a more detailed assessment of the response to natural rewards in methamphetamine (METH) naive versus exposed monkeys during long-term abstinence. Methods: This study introduced an improved sucrose preference test (iSPT) to assess natural reward seeking and consumption in monkeys with long-term abstinence after methamphetamine (METH) use. The test was administered to sixteen naive monkeys and five METH exposed monkeys that had been abstinent for at least 3 months. Results: METH exposed monkeys showed a lower sucrose preference score in both the iSPT (z = -2.10, p = 0.036) and the sucrose preference test (z = -2.61, p = 0.009). The sucrose preference score was significantly correlated with the latency of the establishment of stable sucrose-preference (r = -0.76, df = 46, p < 0.001) but not with the other variables. Furthermore, water-sucrose switch latency and switch times were significantly negatively correlated (r = -0.50, df = 20, p = 0.02). Conclusion: These results show reductions in natural reward consumption during long-term methamphetamine abstinence.

Mechanisms and treatments of methamphetamine and HIV-1 co-induced neurotoxicity: a systematic review.

Combination antiretroviral therapy (cART) has dramatically reduced mortality in people with human immunodeficiency virus (HIV), but it does not completely eradicate the virus from the brain. Patients with long-term HIV-1 infection often show neurocognitive impairment, which severely affects the quality of life of those infected. Methamphetamine (METH) users are at a significantly higher risk of contracting HIV-1 through behaviors such as engaging in high-risk sex or sharing needles, which can lead to transmission of the virus. In addition, HIV-1-infected individuals who abuse METH exhibit higher viral loads and more severe cognitive dysfunction, suggesting that METH exacerbates the neurotoxicity associated with HIV-1. Therefore, this review focuses on various mechanisms underlying METH and HIV-1 infection co-induced neurotoxicity and existing interventions targeting the sigma 1 receptor, dopamine transporter protein, and other relevant targets are explored. The findings of this review are envisaged to systematically establish a theoretical framework for METH abuse and HIV-1 infection co-induced neurotoxicity, and to suggest novel clinical treatment targets.

Pharmacological Treatments for Methamphetamine Use Disorder: Current Status and Future Targets.

The illicit use of the psychostimulant methamphetamine (METH) is a major concern, with overdose deaths increasing substantially since the mid-2010s. One challenge to treating METH use disorder (MUD), as with other psychostimulant use disorders, is that there are no available pharmacotherapies that can reduce cravings and help individuals achieve abstinence. The purpose of the current review is to discuss the molecular targets that have been tested in assays measuring the physiological, the cognitive, and the reinforcing effects of METH in both animals and humans. Several drugs show promise as potential pharmacotherapies for MUD when tested in animals, but fail to produce long-term changes in METH use in dependent individuals (eg, modafinil, antipsychotic medications, baclofen). However, these drugs, plus medications like atomoxetine and varenicline, may be better served as treatments to ameliorate the psychotomimetic effects of METH or to reverse METH-induced cognitive deficits. Preclinical studies show that vesicular monoamine transporter 2 inhibitors, metabotropic glutamate receptor ligands, and trace amine-associated receptor agonists are efficacious in attenuating the reinforcing effects of METH; however, clinical studies are needed to determine if these drugs effectively treat MUD. In addition to screening these compounds in individuals with MUD, potential future directions include increased emphasis on sex differences in preclinical studies and utilization of pharmacogenetic approaches to determine if genetic variances are predictive of treatment outcomes. These future directions can help lead to better interventions for treating MUD.

Correlates of Current Methamphetamine Use and Opioid Co-Use Among Latina Women in a Low-Income Community.

Using data from Proyecto SALTO, a 15-year follow-up study of a cohort of Mexican American women in a low-income community in San Antonio, Texas, this study examines emerging patterns of current methamphetamine (MA) use, including opioid co-use, among this understudied population. A bivariate analysis compared individuals with and without current MA use and identified sociodemographic correlates and co-occurring mental health and substance use. A secondary analysis compared those with current MA use, opioid use, and concurrent MA and opioid use. Nineteen percent of the sample had current MA use. MA use was associated with having a lower income (OR = 7.04-1.93, SE = 1.59-5.46), residential instability (OR = 5.19, SE = 1.99), and suicidal ideation (OR = 2.62, SE = 0.93). Participants with MA use had more than four times the odds of using opioids than those without MA use. Women with concurrent MA and opioid use differed in sociodemographics and behavioral risks compared to those with only MA or only opioid use. These findings explore the social, mental health, and structural inequities that exacerbate risks and harms associated with high-risk substance use among marginalized Latino populations. Prevention and intervention strategies should adopt a holistic approach that considers and addresses polysubstance use, mental health, and the sociocultural contexts in which individuals live.

Structural and Functional Dysregulation of the Brain Endothelium in HIV Infection and Substance Abuse.

Blood-brain barrier (BBB) injury and dysfunction following infection with the human immunodeficiency virus (HIV) enables viral entry into the brain, infection of resident brain cells, neuronal injury and subsequent neurodegeneration leading to HIV-associated neurocognitive disorders (HAND). Although combination antiretroviral therapy has significantly reduced the incidence and prevalence of acquired immunodeficiency syndrome and increased the life expectancy of people living with HIV, the prevalence of HAND remains high. With aging of people living with HIV associated with increased comorbidities, the prevalence of HIV-related central nervous system (CNS) complications is expected to remain high. Considering the principal role of the brain endothelium in HIV infection of the CNS and HAND, the purpose of this manuscript is to review the current literature on the pathobiology of the brain endothelium structural and functional dysregulation in HIV infection, including in the presence of HIV-1 and viral proteins (gp120, Tat, Nef, and Vpr). We summarize evidence from human and animal studies, in vitro studies, and associated mechanisms. We further summarize evidence of synergy or lack thereof between commonly abused substances (cocaine, methamphetamine, alcohol, tobacco, opioids, and cannabinoids) and HIV- or viral protein-induced BBB injury and dysfunction.

Death Due to Caffeine and Methamphetamine Toxicity: A Case Report.

Caffeine (1,3,7-trimethylxanthine) is an over-the-counter psychostimulant that, when used in appropriate amounts, is generally considered safe. However, excessive use can cause various symptoms and, in severe cases, can even be life-threatening. A 34-year-old man with a reported history of psychiatric disorders was found unresponsive at his girlfriend's house and transported to an emergency department. He was presumed to have taken several caffeine pills and was pronounced dead approximately six hours later. There was no evidence of trauma or natural diseases at autopsy. Toxicology testing on hospital blood samples revealed toxic levels of caffeine and methamphetamine. After investigation of the circumstances surrounding the death and accounting for the autopsy and toxicology findings, the cause and manner of death were certified as combined caffeine and methamphetamine toxicity and accident, respectively. Lethal levels of caffeine have been reported when blood concentration exceeds 80 mg/L. Caution is needed to avoid excessive caffeine intake, especially when consumed in concentrated forms like tablets or powders. Caffeine should be used with care not only in cases of cardiovascular disease or genetic vulnerability but also for those with psychiatric disorders. Although deaths from caffeine are rare, they are consistently reported, necessitating attention and caution in its use.

Methamphetamine and Ecstasy-Induced Acute Reversible Cerebellar Neurotoxicity in a 3-Year-Old Child: A Case Report.

The prevalence of substance use disorders is increasing among children and adolescents. We present a case of a 3-year-old girl who was admitted to our hospital with complaints of acute onset difficulty walking and speaking. Neurological examination revealed dysarthria, truncal ataxia, hypotonia, and hyporeflexia. Brain magnetic resonance imaging, cerebrospinal fluid analysis, and routine blood and urine analyses were normal. Urine drug testing revealed positive results for ecstasy and methamphetamine. The patient's symptoms improved during hospitalization. To our knowledge, this is the youngest reported case of methamphetamine and ecstasy-induced acute reversible cerebellar neurotoxicity. It is essential to carefully monitor acute reversible neurological symptoms related to methamphetamine and ecstasy.

The development and validation of a knowledge, attitude, and practice questionnaire of methamphetamine use.

Methamphetamine is a synthetic psychostimulant that is showing a rising trend of usage among adolescents and youths. Its harmful side effects and high risk of developing addiction is a public health problem. Recognizing the knowledge, attitudes, and practices (KAP) on methamphetamine is critical in the planning of an intervention strategy. Currently there is a lack of KAP questionnaires on methamphetamine. The study aims to develop and validate a KAP questionnaire on methamphetamine-use for use among Malaysian adolescents. Following an extensive literature review, face and content validity were carried out among healthcare workers, the public, students, and local subject matter experts. A pilot study was conducted amongst 50 students to assess the test-retest reliability. The questionnaire was then distributed to two groups of 269 and 331 individuals for the Exploratory (EFA) and Confirmatory Factor Analysis (CFA), respectively. The internal reliability was also assessed among these groups. The content validation consisting of Item Content Validity Index (I-CVI, ranging from 0.875 to 1.00), and Scale Content Validity Index (S-CVI/Ave = 0.941) both showed good validation scores. Test-retest reliability showcased an Intraclass Correlation Coefficient (ICC) of > 0.7, indicating its reliability. The model was constructed via the EFA resulting in four constructs, and the model's goodness of fit was confirmed with CFA. An internal reliability was calculated with Cronbach's Alpha and showed acceptable reliability (α-values > 0.6) for all constructs. The KAP questionnaire of methamphetamine use is a valid and reliable tool that can be used among Malaysian adolescents. The model arising from this study, can also be used as a guide for future intervention models for adolescent methamphetamine-use disorder.

A synergistic effect of herb and acupuncture on the methamphetamine.

Background: Herbal medicine Ja-Geum-Jeong (JGJ) has been used for the treatment of detoxification in Eastern Asia. However, the mechanisms involved are not clearly defined. The purpose of the present study was to investigate if herb medication inhibits Methamphetamine (METH)'s reinforcing effect and also examined if a combination of herb medication and acupuncture produces a synergistic effect on METH. Methods: Male Sprague-Dawley rats were given acute METH intraperitoneally and the locomotor activity and ultrasonic vocalization (USV) calls were measured. Rats were administered JGJ orally and acupuncture was given at HT7 or SI5. Monosodium glutamate (MSG) and gamma-aminobutyric acid (GABA) agonists were injected into the Central amygdala (CeA) to investigate a possible neuroscientific mechanism. Tyrosine hydroxylase (TH) and fast scan cyclic voltammetry (FSCV) were measured to immunohistochemically and electrically confirm the behavioral data. Results: Locomotor activity and USV calls were increased by METH (P < 0.05) and these increases were inhibited by JGJ (P < 0.05). Also, JGJ had no effect on the normal group given saline, and acupuncture at SI5 acupoint, but not at HT7 acupoint, produced a synergistic effect when combined with JGJ (P < 0.05). The JGJ's inhibition was blocked by the inactivation of CeA (P < 0.05), and MSG mimicked JGJ (P < 0.05). TH and FSCV measures showed the same pattern with the behavioral data (P < 0.05). Conclusion: Results of the present study suggest that JGJ had inhibitory effects on the METH which was mediated through the activation of CeA and that combination of acupuncture and herb produced synergistic effect.

HIV, inflammation, and initiation of methamphetamine use in sexual and gender minorities assigned male at birth.

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.