Evaluation of the immune system status and hematological dyscrasias, among amphetamine and cannabis abusers at Eradah Hospital in Qassim, Saudi Arabia.

This cross-sectional study aims to evaluate the immune system status and hematological disturbances among individuals who abuse amphetamines and cannabis. Substance abuse, particularly of amphetamines and cannabis, has been associated with various adverse effects on the body, including potential impacts on the immune system and hematological parameters. However, limited research has been conducted to comprehensively assess these effects in a cross-sectional design. Additionally, fungal infections are on the rise internationally, and immune-compromised people are particularly susceptible. The study will recruit a sample of amphetamine and cannabis abusers (n = 50) at the Eradah Hospital in the Qassim Region of Buraydah and assess their sociodemographic and biochemical variables, including blood indices and differential WBC indices, liver, and kidney profiles. Additionally, 50 sputum samples in total were cultured for testing for fungus infections. To obtain the descriptive statistics, the data was imported into Microsoft Excel and subjected to statistical analysis using SPSS 22.0. Amphetamine and cannabis abuser's sociodemographic variables analysis observed that the majority (52%) were aged 18-30, with 56% in secondary school. Unemployment was a significant issue, and most had no other health issues. The majority (50%) had 5-10 years of abuse, while 32% had less than 5 years, and only 18% had been drug abusers for more than 10 years. There were significant changes (p < 0.001) in all different leukocyte blood cells, including neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Furthermore, a microscopic examination of blood films from individuals who misuse the combination of the medications "amphetamine and cannabis" reveals hazardous alterations in Neutrophils. Out of 50, 35 sputum samples showed positive growth on Sabouraud dextrose agar (SDA) with chloramphenicol antibiotic, indicating a unicellular fungal growth. The present study explores the immune system and hematological disturbances linked to amphetamine and cannabis abuse, providing insights into health risks and targeted interventions. The findings complement previous research on drug users' hematological abnormalities, particularly in white blood cells. Routine hematological tests help identify alterations in homeostatic conditions, improving patient knowledge and preventing major issues. Further research is needed on multi-drug abuse prevention, early detection, and intervention. The cross-sectional design allows for a snapshot of the immune system and hematological status among abusers, laying the groundwork for future longitudinal studies. Key Words: Drug Effect, Immunity, Epidemiology, Oxidative Stress, Inflammation.

Changes in injecting versus smoking heroin, fentanyl, and methamphetamine among people who inject drugs in San Diego, California, 2020-2023.

BACKGROUND: Amidst an increasingly toxic drug supply in North America, people who inject drugs may be transitioning to smoking them. We aimed to assess changes in injecting and smoking opioids and methamphetamine among a cohort of people who inject drugs from San Diego, California. METHODS: Over five six-month periods spanning October 2020-April 2023, we assessed prevalence of injecting and smoking opioids or methamphetamine and whether participants used these drugs more frequently by smoking than injecting. Multivariable Poisson regression via generalized estimating equations was used to examine time trends. RESULTS: Of 362 participants, median age was 40 years; a minority were female (29%), Hispanic/Latinx/Mexican (45%), and housed (33%). Among this cohort, of whom 100% injected (and 84% injected and smoked) in period one (October 2020-April 2021), by period five (November 2022-April 2023), 34% only smoked, 59% injected and smoked, and 7% only injected. By period five, the adjusted relative risk (aRR) of injecting opioids was 0.41 (95% Confidence Interval [CI]: 0.33, 0.51) and the aRR for injecting methamphetamine was 0.50 (95% CI: 0.39, 0.63) compared to period one. Risks for smoking fentanyl rose significantly during period three (aRR=1.44, 95% CI: 1.06, 1.94), four (aRR=1.65, 95% CI: 1.24, 2.20) and five (aRR=1.90, 95% CI: 1.43, 2.53) compared to period one. Risks for smoking heroin and methamphetamine more frequently than injecting these drugs increased across all periods. CONCLUSIONS: Opioid and methamphetamine injection declined precipitously, with notable increases in smoking these drugs. Research is needed to understand the health consequences of these trends.

Methamphetamine Enhancement of HIV-1 gp120-Mediated NLRP3 Inflammasome Activation and Resultant Proinflammatory Responses in Rat Microglial Cultures.

Human Immunodeficiency Virus type 1 (HIV-1)-associated neurocognitive disorders (HANDs) remain prevalent in HIV-1-infected individuals despite the evident success of combined antiretroviral therapy (cART). The mechanisms underlying HAND prevalence in the cART era remain perplexing. Ample evidence indicates that HIV-1 envelope glycoprotein protein 120 (gp120), a potent neurotoxin, plays a pivotal role in HAND pathogenesis. Methamphetamine (Meth) abuse exacerbates HANDs, but how this occurs is not fully understood. We hypothesize that Meth exacerbates HANDs by enhancing gp120-mediated neuroinflammation. To test this hypothesis, we studied the effect of Meth on gp120-induced microglial activation and the resultant production of proinflammatory cytokines in primary rat microglial cultures. Our results show that Meth enhanced gp120-induced microglial activation, as revealed by immunostaining and Iba-1 expression, and potentiated gp120-mediated NLRP3 expression and IL-1ß processing and release, as assayed by immunoblotting and ELISA. Meth also augmented the co-localization of NLRP3 and caspase-1, increased the numbers of NLRP3 puncta and ROS production, increased the levels of iNOS expression and NO production, and increased the levels of cleaved gasderminD (GSDMD-N; an executor of pyroptosis) in gp120-primed microglia. The Meth-associated effects were attenuated or blocked by MCC950, an NLRP3 inhibitor, or Mito-TEMPO, a mitochondrial superoxide scavenger. These results suggest that Meth enhances gp120-associated microglial NLRP3 activation and the resultant proinflammatory responses via mitochondria-dependent signaling.

Alterations in the fecal microbiota of methamphetamine users with bad sleep quality during abstinence.

BACKGROUND: Methamphetamine (MA) abuse has resulted in a plethora of social issues. Sleep disturbance is a prominent issue about MA addiction, which serve as a risk factor for relapse, and the gut microbiota could play an important role in the pathophysiological mechanisms of sleep disturbances. Therefore, improving sleep quality can be beneficial for treating methamphetamine addiction, and interventions addressing the gut microbiota may represent a promising approach. METHOD: We recruited 70 MA users to investigate the associations between sleep quality and fecal microbiota by the Pittsburgh Sleep Quality Index (PSQI), which was divided into MA-GS (PSQI score < 7, MA users with good sleep quality, n = 49) and MA-BS group (PSQI score ≥ 7, MA users with bad sleep quality, n = 21). In addition, we compared the gut microbiota between the MA-GS and healthy control (HC, n = 38) groups. 16S rRNA sequencing was applied to identify the gut bacteria. RESULT: The study revealed that the relative abundances of the Thermoanaerobacterales at the order level differed between the MA-GS and MA-BS groups. Additionally, a positive correlation was found between the relative abundance of the genus Sutterella and daytime dysfunction. Furthermore, comparisons between MA users and HCs revealed differences in beta diversity and relative abundances of various bacterial taxa. CONCLUSION: In conclusion, the study investigated alterations in the gut microbiota among MA users. Furthermore, we demonstrated that the genus Sutterella changes may be associated with daytime dysfunction, suggesting that the genus Sutterella may be a biomarker for bad sleep quality in MA users.

Hereditary and cortical morphological biomarker of sensitivity to reward in short-term withdrawal methamphetamine abusers.

Higher sensitivity to reward (SR) and weaker sensitivity to punishment (SP) construct the fundamental craving characteristics of methamphetamine abuse. However, few studies have appraised relationships between SR/SP (SR or SP) and cortical morphological alterations in methamphetamine abusers and whether hereditary factors take effects on SR/SP is unclear. Based on surface-based morphometric analysis, cortical discrepancy was investigated between 38 methamphetamine abusers and 37 healthy controls. Within methamphetamine abusers, correlation profiling was performed to discover associations among aberrant neuroimaging substrates, SR, SP, and craving. According to nine single nucleotide polymorphism sites of dopamine-related genes, we conducted univariate general linear model to find different effects of genotypes on cortical alterations and SR/SP/craving (SR, SP, or craving). Ultimately, mediation analyses were conducted among single nucleotide polymorphism sites, SR/SP/craving, and cortical morphological alterations to discover their association pathways. Compared to healthy controls, thinner cortices in inferior temporal gyrus, lateral orbitofrontal cortex, medial orbitofrontal cortex, inferior parietal lobule, and lateral occipital cortex in the left hemisphere were found in methamphetamine abusers (P < 0.05, family-wise error corrected). Cortical thickness in the inferior temporal gyrus was negatively correlated with SR scores. We found that rs1800497 A-containing genotypes had lower cortical thickness in the left inferior parietal lobule than the GG genotype. The rs5751876 had effects on SR scores. This study would provide convincing biomarkers for SR in methamphetamine abusers and offer potential genetic targets for personalizing relapse prevention.

Lycium barbarum polysaccharide mitigated methamphetamine addiction and altered methamphetamine-induced gut microbiota dysbiosis.

Methamphetamine (MA) is a highly addictive mental stimulant, and MA abuse remains a significant public health problem worldwide, while effective treatment options are limited. Lycium barbarum polysaccharide (LBP), a major effective component extracted from Lycium barbarum, has potential health-promoting effects on the nervous system; however, its role in MA dependence remains unclear. In this study, the conditioned place preference (CPP) of MA addiction in adult male mice was established to detect changes in gut microbiota profiles after LBP treatment through 16S rRNA gene sequencing. Our results found that LBP administration could alleviate MA-induced CPP and hyperactivity. Interestingly, LBP improved MA-induced gut microbiota dysbiosis by increasing some beneficial autochthonous genus abundances, such as Allobaculum, Gordonibacter, and Ileibacterium. MA exposure induced the co-occurrence network of intestinal microbiota to become weaker and more unstable when compared with the control group, while LBP changed the above effects when compared with the MA group. Bacterial gene function prediction showed that amphetamine addiction, cocaine addiction, and short-chain fatty acid metabolism were enriched. These findings reveal that LBP might regulate MA-induced gut microbiota and behavior changes, which showed potential therapeutic applicability in treating MA addiction by regulating the gut microbiota.

Positive and negative symptoms in methamphetamine-induced psychosis compared to schizophrenia: A systematic review and meta-analysis.

BACKGROUND: The clinical profiles of methamphetamine-induced psychosis (MIP) and schizophrenia are largely overlapping making differentiation challenging. In this systematic review and meta-analysis, we aim to compare the positive and negative symptoms of MIP and schizophrenia to better understand the differences between them. STUDY DESIGN: In accordance with our pre-registered protocol (CRD42021286619), we conducted a search of English-language studies up to December 16th, 2022, in PubMed, EMBASE, and PsycINFO, including stable outpatients with MIP and schizophrenia. We used the Newcastle-Ottawa Scale to measure the quality of cross-sectional, case-control, and cohort studies. STUDY RESULTS: Of the 2052 articles retrieved, we included 12 studies (6 cross-sectional, 3 case-control, and 2 cohort studies) in our meta-analysis, involving 624 individuals with MIP and 524 individuals with schizophrenia. Our analysis found no significant difference in positive symptoms between the two groups (SMD, -0.01; 95%CI, -0.13 to +0.11; p = 1). However, individuals with MIP showed significantly less negative symptoms compared to those with schizophrenia (SMD, -0.35; 95CI%, -0.54 to -0.16; p = 0.01; I2 = 54 %). Our sensitivity analysis, which included only studies with a low risk of bias, did not change the results. However, our meta-analysis is limited by its cross-sectional approach, which limits the interpretation of causal associations. Furthermore, differences in population, inclusion criteria, methodology, and drug exposure impact our findings. CONCLUSIONS: Negative symptoms are less prominent in individuals with MIP. While both groups do not differ regarding positive symptoms, raises the possibility of shared and partly different underlying neurobiological mechanisms related to MIP and schizophrenia.

Participant experiences in a pilot study for methamphetamine withdrawal treatment: Implications for retention.

INTRODUCTION: There is little knowledge of the perspectives of people who use methamphetamine and have participated in clinical trials, and none for interventions not intended to address abstinence. A better understanding of these experiences could lead to more patient centred clinical trial design. This study seeks to understand the experiences of people who completed a clinical trial of lisdexamfetamine for the treatment of acute methamphetamine withdrawal. METHODS: Thematic analysis of open-ended, semi-structured interviews with eight people who participated in an inpatient clinical trial of lisdexamfetamine for acute methamphetamine withdrawal. Interviews were conducted between days 3 and 6 of admission to an inner-city Sydney hospital. RESULTS: Participants described how research procedures, the research setting, and the investigational product affected their experiences while enrolled in a clinical trial. Of particular importance to participants were transparent and low burden trial procedures, a welcoming trial environment, trusting relationships and effective communication, which were linked with the participants' subsequent decision to remain enrolled in the trial. DISCUSSION: The experiences of participants in this clinical trial can be distilled into four meta-themes: agency, caring-trust, safety, and communication. Participants spontaneously linked these experiences with a capacity to remain enrolled in the study. By considering the experiences of trial participants in clinical trial design, researchers can improve the experiences of future trial participants and facilitate their choice to remain enrolled in clinical trials.

Methamphetamine intoxication and suicidal ideation/behavior in the emergency department.

BACKGROUND: This study investigates the association between Methamphetamine (MA) intoxication and suicidal ideation/behavior in patients presenting to emergency departments. Amidst rising MA use and co-use with opioids, this "twin epidemic" has manifested in increasing admissions for MA intoxication, often accompanied by psychiatric symptoms that can escalate to suicidal behaviors. METHOD: This retrospective study utilized patient records and analyzed data from 629 patients admitted to a Texas emergency department in 2020, with MA intoxication confirmed via urine tests and patient interviews. The suicidal tendencies were assessed using the Columbia-Suicide Severity Scale. The 629 patients were divided into three groups for analysis: Group I (n = 188), MA positive with suicidal ideation (SI) (MA + SI+); Group II (n = 202), MA-positive without SI (MA + SI-); and Group III (n = 239), MA-negative with SI (MA- SI+). Multiple regression analysis was used to elicit clinical features predicting patients presenting to the emergency department with acute MA intoxication. RESULTS: Results reveal that approximately half of patients with acute MA intoxication reported suicidal thoughts, indicating a significant association between MA use and suicidal tendencies. Females exhibited higher rates of suicidal thoughts, behavior, and subsequent medical attention compared to males. Sociodemographic characteristics and clinical features differed among MA-positive patients with and without SI. Multivariable regression analysis identified factors influencing MA use, including cannabis use, male gender, agitation, and an inverse association with alcohol use. Notably, the severity and potential lethality of suicidal behavior in MA-intoxicated patients paralleled those observed in psychiatric patients without MA use. CONCLUSION: These results underscore the urgent need for targeted interventions to address the complex interplay between MA use and suicidal risks in the emergency department setting, as well as broader public health strategies to combat the increasing prevalence of MA use.

Epigenome-wide association study on methamphetamine dependence.

Repeated abuse of methamphetamine (METH) can cause dependence, repeated relapse of psychotic symptoms, compulsive drug-seeking behaviour, and various neurological symptoms. These long-term biological changes may be associated with epigenetic mechanisms; however, the association between METH use and epigenetic mechanisms has been poorly investigated. Thus, we performed an epigenome-wide association study of METH dependence using genomic DNA extracted from the blood samples of 24 patients with METH dependence and 24 normal controls. All participants were of Japanese descent. We tested the association between METH dependence and DNA methylation using linear regression analysis. We found epigenome-wide significant associations at four CpG sites, one of which occurred in the CNOT1 gene and another in the PUM1 gene. We especially noted the CNOT1 and PUM1 genes as well as several other genes that indicated some degree of association with METH dependence. Among the relatively enriched Gene Ontology terms, we were interested in terms of mRNA metabolism, respirasome, and excitatory extracellular ligand-gated ion channel activity. Among the relatively enriched Kyoto Encyclopedia of Genes and Genome pathways, we noted pathways of several neurological diseases. Our results indicate that genetic changes akin to those in other psychiatric or neurodegenerative disorders may also occur via epigenetic mechanisms in patients with METH dependence.

SMART Family and Friends: Feasibility and outcomes of a video-conference delivered intervention for families impacted by another's methamphetamine use.

INTRODUCTION: Families affected by another's substance use, including methamphetamine, experience harms to their mental and physical health. Yet, research has paid little attention to support and service needs of this population. This pilot study examines the feasibility and outcomes of SMART Family and Friends, a video-conference-delivered mutual-support group targeting families affected by another's methamphetamine use. METHODS: Recruitment for this study occurred between March-October 2021 via the SMART Recovery Australia website. Participants were English-speaking Australian residents, ≥18 years, affected by another's methamphetamine use, interested in participating in a manualised eight-module group delivered via video-conferencing. Feasibility was evaluated by attendance rates, participant satisfaction, fidelity ratings, and semi-structured interviews. Measures of distress, quality of life, and family functioning assessed outcomes at baseline and one-month post-treatment conclusion. RESULTS: Forty-three participants commenced SMART Family and Friends groups. 84 % (n = 36) completed ≥4 modules, 67 % (n = 29) completed ≥6, and 42 % (n = 18) completed all 8 modules. Participant satisfaction (M = 4.32, SD = 0.66, out of 5) and facilitator fidelity (>94 % for all modules) were high. A within-group analysis, without comparison condition demonstrated significant improvements in psychological distress (d = 0.38), family impact (d = 0.64), family strain symptoms (d = 0.48), and total family burden (d = 0.69) post-treatment. Qualitative findings illustrated the benefits and challenges of the video-conference-delivered group, as well as recommendations for improvement. CONCLUSIONS: Results provide initial support for the feasibility and positive outcomes of the SMART Family and Friends program. These findings demonstrate the successful provision of a mutual-support group for affected families delivered via video-conferencing, and merit further sufficiently powered randomised-control-trials to evaluate efficacy.

Modeling methamphetamine use disorder in mammals: Sex differences in behavioral, biochemical, and transcriptional consequences.

Methamphetamine (METH) is the most commonly misused amphetamine-type stimulant throughout the globe. METH is very rewarding, and its misuse can lead to a diagnosis of METH use disorder (MUD). Although METH use is observed in both sexes, there are, however, reported differences in the clinical manifestations of METH use and its consequences. These observations indicate the need for more research on the long-term sex-dependent consequences of METH taking in both preclinical and clinical settings. In effect, sex is a biological variable that can impact conclusions drawn from various basic and clinical studies. Thus, the present chapter provides a succinct review of the current state of the research on METH and its sex-associated consequences. In addition to behavioral and cognitive aspects of METH use, we discuss METH-induced changes in neurotransmitter systems and structures in the brain. Thus, the book chapter serves to highlight the significance of sex as a critical element that needs to be considered during discussions of novel therapeutic approaches to MUD.

The role of sex and drug use during adolescence in determining the risk for adverse consequences of amphetamines.

Use of amphetamines during adolescence, a critical period of brain development and reorganization, may lead to particularly adverse outcomes that are long-lasting. Similarly, female users may be uniquely vulnerable to certain aspects of drug use. A recognition of the role of use during adolescence and sex on outcomes of amphetamine and methamphetamine exposure are of critical importance in understanding and treating substance use disorders. This chapter highlights what human research, which has been largely epidemiological, suggests about sex and age differences in drug use patterns and outcomes. We also discuss work in laboratory animals that has typically utilized rats or mice exposed to drugs in a non-contingent manner (i.e., involuntarily) or through volitional self-administration. Lastly, we draw attention to the fact that advancing our understanding of the effects of amphetamine and methamphetamine use, the development of problematic drug taking, and the mechanisms that contribute to relapse will require an emphasis on inclusion of age and sex as moderating factors in future studies.

Associations between impulsivity and fecal microbiota in individuals abstaining from methamphetamine.

INTRODUCTION: Methamphetamine (MA) abuse is a major public problem, and impulsivity is both a prominent risk factor and a consequence of addiction. Hence, clarifying the biological mechanism of impulsivity may facilitate the understanding of addiction to MA. The microbiota-gut-brain axis was suggested to underlie a biological mechanism of impulsivity induced by MA. METHODS: We therefore recruited 62 MA addicts and 50 healthy controls (HCs) to investigate the alterations in impulsivity and fecal microbiota and the associations between them in the MA group. Thereafter, 25 MA abusers who abstained from MA for less than 3 months were followed up for 2 months to investigate the relationship between impulsivity and microbiota as abstinence became longer. 16S rRNA sequencing was conducted for microbiota identification. RESULTS: Elevated impulsivity and dysbiosis characterized by an increase in opportunistic pathogens and a decrease in probiotics were identified in MA abusers, and both the increased impulsivity and disrupted microbiota tended to recover after longer abstinence from MA. Impulsivity was related to microbiota, and the effect of MA abuse on impulsivity was mediated by microbiota. CONCLUSION: Our findings potentially highlighted the importance of abstention and implicated the significant role of the microbiota-gut-brain axis in the interrelationship between microbiota and behaviors, as well as the potential of microbiota as a target for intervention of impulsivity.

Dopaminergic dominance in the ventral medial hypothalamus: A pivotal regulator for methamphetamine-induced pathological aggression.

Methamphetamine (METH) abuse is associated with a spectrum of behavioral consequences, among which heightened aggression presents a significant challenge. However, the causal role of METH's impact in aggression and its target circuit mechanisms remains largely unknown. We established an acute METH exposure-aggression mouse model to investigate the role of ventral tegmental area (VTA) dopaminergic neurons and ventral medial hypothalamus VMH glutamatergic neuron. Our findings revealed that METH-induced VTA dopamine excitability activates the ventromedial hypothalamus (VMH) glutamatergic neurons, contributing to pathological aggression. Notably, we uncovered a dopaminergic transmission within the VTA-VMH circuit that exclusively functioned under METH influence. This dopaminergic pathway emerged as a potential key player in enabling dopamine-related pathological aggression, with heightened dopaminergic excitability implicated in various psychiatric symptoms. Also, the modulatory function of this pathway opens new possibilities for targeted therapeutic strategies for intervention to improve treatment in METH abuse and may have broader implications for addressing pathological aggression syndromes.

Alterations in the brain functional network of abstinent male individuals with methamphetamine use disorder.

Methamphetamine is a highly addictive psychostimulant drug that is abused globally and is a serious threat to health worldwide. Unfortunately, the specific mechanism underlying addiction remains unclear. Thus, this study aimed to investigate the characteristics of functional connectivity in the brain network and the factors influencing methamphetamine use disorder in patients using magnetic resonance imaging. We included 96 abstinent male participants with methamphetamine use disorder and 46 age- and sex-matched healthy controls for magnetic resonance imaging. Compared with healthy controls, participants with methamphetamine use disorder had greater impulsivity, fewer small-world attributes of the resting-state network, more nodal topological attributes in the cerebellum, greater functional connectivity strength within the cerebellum and between the cerebellum and brain, and decreased frontoparietal functional connectivity strength. In addition, after controlling for covariates, the partial correlation analysis showed that small-world properties were significantly associated with methamphetamine use frequency, psychological craving, and impulsivity. Furthermore, we revealed that the small-word attribute significantly mediated the effect of methamphetamine use frequency on motor impulsivity in the methamphetamine use disorder group. These findings may further improve our understanding of the neural mechanism of impulse control dysfunction underlying methamphetamine addiction and assist in exploring the neuropathological mechanism underlying methamphetamine use disorder-related dysfunction and rehabilitation.

Impact of miR-29c-3p in the Nucleus Accumbens on Methamphetamine-Induced Behavioral Sensitization and Neuroplasticity-Related Proteins.

Methamphetamine (METH) abuse inflicts both physical and psychological harm. While our previous research has established the regulatory role of miR-29c-3p in behavior sensitization, the underlying mechanisms and target genes remain incompletely understood. In this study, we employed the isobaric tags for relative and absolute quantitation (iTRAQ) technique in conjunction with Ingenuity pathway analysis (IPA) to probe the putative molecular mechanisms of METH sensitization through miR-29c-3p inhibition. Through a microinjection of AAV-anti-miR-29c-3p into the nucleus accumbens (NAc) of mice, we observed the attenuation of METH-induced locomotor effects. Subsequent iTRAQ analysis identified 70 differentially expressed proteins (DEPs), with 22 up-regulated potential target proteins identified through miR-29c-3p target gene prediction and IPA analysis. Our focus extended to the number of neuronal branches, the excitatory synapse count, and locomotion-related pathways. Notably, GPR37, NPC1, and IREB2 emerged as potential target molecules for miR-29c-3p regulation, suggesting their involvement in the modulation of METH sensitization. Quantitative PCR confirmed the METH-induced aberrant expression of Gpr37, Npc1, and Ireb2 in the NAc of mice. Specifically, the over-expression of miR-29c-3p led to a significant reduction in the mRNA level of Gpr37, while the inhibition of miR-29c-3p resulted in a significant increase in the mRNA level of Gpr37, consistent with the regulatory principle of miRNAs modulating target gene expression. This suggests that miR-29c-3p potentially influences METH sensitization through its regulation of neuroplasticity. Our research indicates that miR-29c-3p plays a crucial role in regulating METH-induced sensitization, and it identified the potential molecular of miR-29c-3p in regulating METH-induced sensitization.

Model-based and model-free mechanisms in methamphetamine use disorder.

People with methamphetamine use disorder (MUD) struggle to shift their behaviour from methamphetamine-orientated habits to goal-oriented choices. The model-based/model-free framework is well suited to understand this difficulty by unpacking the computational mechanisms that support experienced-based (model-free) and goal-directed (model-based) choices. We aimed to examine whether 1) participants with MUD differed from controls on behavioural proxies and/or computational mechanisms of model-based/model-free choices; 2) model-based/model-free decision-making correlated with MUD symptoms; and 3) model-based/model-free deficits improved over six weeks in the group with MUD. Participants with MUD and controls with similar age, IQ and socioeconomic status completed the Two-Step Task at treatment commencement (MUD n = 30, Controls n = 31) and six weeks later (MUD n = 23, Controls n = 26). We examined behavioural proxies of model-based/model-free decisions using mixed logistic regression, and their underlying mechanisms using computational modelling. At a behavioural level, participants with MUD were more likely to switch their choices following rewarded actions, although this pattern improved at follow up. At a computational level, groups were similar in their use of model-based mechanisms, but participants with MUD were less likely to apply model-free mechanisms and less likely to repeat rewarded actions. We did not find evidence that individual differences in model-based or model-free parameters were associated with greater severity of methamphetamine dependence, nor did we find that group differences in computational parameters changed between baseline and follow-up assessment. Decision-making challenges in people with MUD are likely related to difficulties in pursuing choices previously associated with positive outcomes.