Oral Microbiota Profile of Individuals Who Abuse Methamphetamine.
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ABSTRACT:
SUBMITTER: Yang Y
PROVIDER: S-EPMC8461105 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:As a severe public health problem, methamphetamine (METH) abuse places a heavy burden on families and society. A growing amount of evidence has indicated communication between gut microbiota and the CNS in drug addiction, with associations to neural, endocrine and immune pathways. Thus, we searched for alterations in the gut microbiota and their potential effects in METH users through 16S rRNA gene sequencing. A decreased Shannon index indicated lower bacterial diversity in the METH users than in the age-matched control group. The gut microbial community composition in the METH users was also altered, including reductions in Deltaproteobacteria and Bacteroidaceae abundances and increases in Sphingomonadales, Xanthomonadales, Romboutsia and Lachnospiraceae abundances. Moreover, the Fusobacteria abundance was correlated with the duration of METH use. Enterobacteriaceae, Ruminococcaceae, Bacteroides, and Faecalibacterium had statistically significant correlations with items related to the positive and negative symptoms of schizophrenia and to general psychopathology in the METH users, and all have previously been reported to be altered in individuals with psychotic syndromes, especially depression. Abstraction, one of the items of the cognitive assessment, was positively related to Blautia. These findings revealed alterations in the gut microbiota of METH users, and these alterations may play a role in psychotic syndrome and cognitive impairment. Although the mechanisms behind the links between these disorders and METH abuse are unknown, the relationships may indicate similarities in the pathogenesis of psychosis induced by METH abuse and other causes, providing a new paradigm for addiction and METH use disorder treatment.
| S-EPMC8437956 | biostudies-literature
Project description:BackgroundThe transition from methamphetamine (MA) casual use (MCU) to compulsive use is enigmatic as some MA users can remain in casual use, but some cannot. There is a knowledge gap if gut microbiota (GM) play a role in differing MCU from MA use disorder (MUD). We aimed to investigate the clinical features and GM differences between individuals with MCU and MUD.MethodWe recruited two groups of MA users -MCU and MUD - and matched them according to age and body mass index (n=21 in each group). Participants were accessed using the Semi-Structured Assessment for Drug Dependence and Alcoholism, and their fecal samples were undergone 16S ribosomal DNA sequencing. We compared the hosts' clinical features and GM diversity, composition, and structure (represented by enterotypes) between the two groups. We have identified differential microbes between the two groups and performed network analyses connecting GM and the clinical traits.ResultCompared with the casual users, individuals with MUD had higher incidences of MA-induced neuropsychiatric symptoms (e.g., paranoia, depression) and withdrawal symptoms (e.g., fatigue, drowsiness, and increased appetite), as well as stronger cravings for and intentions to use MA, and increased MA tolerance. The GM diversity showed no significant differences between the two groups, but four genera (Halomonas, Clostridium, Devosia, and Dorea) were enriched in the individuals with MUD (p<0.05). Three distinct enterotypes were identified in all MA users, and Ruminococcus-driven enterotype 2 was dominant in individuals with MUD compared to the MCU (61.90% vs. 28.60%, p=0.03). Network analysis shows that Devosia is the hub genus (hub index = 0.75), which is not only related to the counts of the MUD diagnostic criteria (ρ=0.40; p=0.01) but also to the clinical features of MA users such as reduced social activities (ρ=0.54; p<0.01). Devosia is also associated with the increased intention to use MA (ρ=0.48; p<0.01), increased MA tolerance (ρ=0.38; p=0.01), craving for MA (ρ=0.37; p=0.01), and MA-induced withdrawal symptoms (p<0.05).ConclusionOur findings suggest that Ruminococcus-driven enterotype 2 and the genera Devosia might be two influential factors that differentiate MA casual use from MUD, but further studies are warranted.
| S-EPMC9996337 | biostudies-literature
Project description:Pharmacological treatment for methamphetamine addiction will provide important societal benefits. Neurotensin receptor NTR1 and dopamine receptor distributions coincide in brain areas regulating methamphetamine-associated reward, and neurotensin peptides produce behaviors opposing psychostimulants. Therefore, undesirable methamphetamine-associated activities should be treatable with druggable NTR1 agonists, but no such FDA-approved therapeutics exist. We address this limitation with proof-of-concept data for ML314, a small-molecule, brain penetrant, ?-arrestin biased, NTR1 agonist. ML314 attenuates amphetamine-like hyperlocomotion in dopamine transporter knockout mice, and in C57BL/6J mice it attenuates methamphetamine-induced hyperlocomotion, potentiates the psychostimulant inhibitory effects of a ghrelin antagonist, and reduces methamphetamine-associated conditioned place preference. In rats, ML314 blocks methamphetamine self-administration. ML314 acts as an allosteric enhancer of endogenous neurotensin, unmasking stoichiometric numbers of hidden NTR1 binding sites in transfected-cell membranes or mouse striatal membranes, while additionally supporting NTR1 endocytosis in cells in the absence of NT peptide. These results indicate ML314 is a viable, preclinical lead for methamphetamine abuse treatment and support an allosteric model of G protein-coupled receptor signaling.
| S-EPMC4947017 | biostudies-literature
Project description:ObjectivesTo describe the oral health profile of individuals who had undergone gastric bypass surgery (GBP) or sleeve gastrectomy (SG) to generate hypotheses for further studies.Material and methodsFourteen individuals treated with GBP or SG surgery ≥ 2 years ago and with observed and/or perceived oral problems were recruited to a case series. The documentation included clinical and radiographic examinations, biomedical sampling, and self-reported diet and questionnaires. The results are presented descriptively.ResultsThe age range was 31 to 66 years and all had a BMI > 25 (range 25.4-44.7). Only four participants were fully dentate. Eleven out of 14 individuals exhibited severe decay. A majority had poor oral hygiene and high bacterial counts. The flow rates of unstimulated saliva were extremely low and hyposalivation was present in ten of the fourteen cases. Most perceived several oral health problems, such as chewing difficulty and tooth hypersensitivity.ConclusionsIndividuals who had undergone GBP or SG surgery had poor clinically diagnosed oral health and perceived oral health problems. Longitudinal studies are needed to monitor the patients' oral health, from before bariatric surgery to long-term postoperatively.
| S-EPMC8543454 | biostudies-literature
Project description:PurposeTo perform a pilot clinical trial of bupropion for methamphetamine abuse/dependence among adolescents.MethodsNineteen adolescents with methamphetamine abuse (n = 2) or dependence (n = 17) were randomly assigned to bupropion SR 150 mg twice daily or placebo for 8 weeks with outpatient substance abuse counseling.ResultsBupropion was well-tolerated except for one female in the bupropion group who was hospitalized for suicidal ideation during a methamphetamine relapse. Adolescents receiving bupropion and females provided significantly fewer methamphetamine-free urine tests compared to participants receiving placebo (p = .043) and males (p = .005) respectively.ConclusionsResults do not support the feasibility of additional trials of bupropion for adolescent methamphetamine abuse/dependence. Future studies should investigate the influence of gender on adolescent methamphetamine abuse and treatment outcomes.
| S-EPMC3608805 | biostudies-literature
Project description:Oral microbiota ecology is influenced by environmental and host conditions, but few studies have evaluated associations between untargeted measures of the entire oral microbiome and potentially relevant environmental and host factors. This study aimed to identify salivary microbiota cluster groups using hierarchical cluster analyses (Wards method) based on 16S rRNA gene amplicon sequencing, and identify lifestyle and host factors which were associated with these groups. Group members (n = 175) were distinctly separated by microbiota profiles and differed in reported sucrose intake and allelic variation in the taste-preference-associated genes TAS1R1 (rs731024) and GNAT3 (rs2074673). Groups with higher sucrose intake were either characterized by a wide panel of species or phylotypes with fewer aciduric species, or by a narrower profile that included documented aciduric- and caries-associated species. The inferred functional profiles of the latter type were dominated by metabolic pathways associated with the carbohydrate metabolism with enrichment of glycosidase functions. In conclusion, this study supported in vivo associations between sugar intake and oral microbiota ecology, but it also found evidence for a variable microbiota response to sugar, highlighting the importance of modifying host factors and microbes beyond the commonly targeted acidogenic and acid-tolerant species. The results should be confirmed under controlled settings with comprehensive phenotypic and genotypic data.
| S-EPMC7146170 | biostudies-literature
Project description:Methamphetamine (MA) is a highly addictive stimulant with recent upward trends in prevalence and associated public health problems. Drug demand, as assessed by hypothetical purchasing tasks, has been useful in addictions research and may help our understanding of the factors influencing MA use. However, no studies have assessed MA demand using current models of demand. The purpose of the current study was to assess demand for MA using a hypothetical drug purchasing task. Given high rates of cigarette smoking among MA users, it was of interest also to assess and compare demand for MA relative to cigarettes. Participants consisted of non-treatment-seeking volunteers with MA use disorder (N = 18), of whom 17 reported daily smoking. Results showed the exponentiated demand model provided a good fit to consumption data. Results from Bayesian generalized linear modeling demonstrated multiple positive relationships (posterior probability ≥75%) between self-reported drug use (days MA used in the past 30 days, cigarettes smoked per day) and indices of demand for each drug (Qo, Omax, Pmax, and break point). Comparing MA to cigarettes, results from Bayesian generalized linear mixed modeling revealed greater abuse liability for MA compared to cigarettes (posterior probability ≥99%) based on α and essential value. Overall, the findings of the current study support the feasibility and validity of the exponentiated demand model for assessing demand for drugs among individuals with MA use disorder. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
| S-EPMC7508771 | biostudies-literature
Project description:Methamphetamine (METH) is a drug with high abuse potential that directly affects the central nervous system. METH use leads not only to detrimental health for the user but also to potential risks and costs for society. Impaired cognition has been shown to exist in individuals with long-term METH dependence, and this impairment may be the main cause of impulsive drug taking and high relapse rate. However, the molecular mechanisms underlying METH addiction and METH-induced cognitive decline remain unknown. To investigate potential molecular mechanisms of METH addiction, we compared serum protein expression levels by using label-free quantitative proteomics in 12 long-term METH users and 12 healthy control participants. In total, 23 differentially expressed proteins were found between the two groups. Bioinformatics analyses were used to identify functional networks and protein-protein interactions. The differentially expressed proteins were related to cognitive dysfunction, inflammation of the nervous system, immune system decline, energy metabolism, and calcium binding and regulation. Thus, these 23 proteins may be closely associated with the damage caused by METH to the nervous, immune, and metabolic systems. The results of this study provide additional insights into the molecular mechanisms of METH addiction and potential prevention and treatment options for METH-dependent individuals.
2023-02-14 | PXD040112 |
Project description:BACKGROUND:Although hair testing is well established for the assessment of past drug exposure, uncertainties persist about mechanisms of drug incorporation into hair and interpretation of results. The aim of this study was to administer methamphetamine (MAMP) under controlled conditions as a model drug to investigate drug incorporation into human hair. MATERIAL AND METHODS:Seven volunteers with a history of stimulant use received 4×10 mg (low) doses of sustained release S-(+)-MAMP HCl within 1 week, with weekly head hair samples collected by shaving. 3 weeks later, 4 of them received 4×20 mg (high) doses. After extensive isopropanol/phosphate buffer washing of the hair, MAMP and its metabolite amphetamine (AMP) concentrations were determined in all weekly hair samples by LC-MS-MS in selected reaction monitoring mode with the undeca- and deca-deuterated drugs, respectively, as internal standards (LLOQ, 0.005 ng mg(-1)). RESULTS:MAMP T(max) occurred from 1 to 2 weeks after both doses, with C(max) ranging from 0.6 to 3.5 ng mg(-1) after the low and 1.2 to 5.3 ng mg(-1) after the high MAMP doses. AMP C(max) in hair was 0.1-0.3 ng mg(-1) and 0.2-0.5 ng mg(-1), respectively, for low and high doses. Highly dose-related concentrations within subjects, but large variability between subjects were observed. MAMP concentrations were above the 0.2 ng mg(-1) cut-off for at least 2 weeks following administration of both low and high doses. The overall AMP/MAMP ratio ranged from 0.07 to 0.37 with a mean value of 0.15 ± 0.07, and a median of 0.13. The percentage of MAMP and AMP removed with the washing procedure decreased with time after administration. A strong correlation was found between area under the curve of MAMP (r(2)=0.90, p=0.00) and AMP (r(2)=0.94, p=0.00) concentrations calculated for the 3-week period following administration and the total melanin concentration in hair. Significant correlations were observed also between C(max) and melanin. CONCLUSIONS:This study demonstrated that despite large inter-individual differences, the incorporation of MAMP and AMP into hair is dose-related with much of the observed scatter of MAMP and AMP concentrations explained by melanin concentration in hair.
| S-EPMC3391534 | biostudies-literature
Project description:Chronic methamphetamine use may lead to changes in reward-related function of the ventral striatum and caudate nucleus. Whether methamphetamine-dependent individuals show heightened reactivity to positively valenced stimuli (i.e. positive reinforcement mechanisms), or an exaggerated response to negatively valenced stimuli (i.e. driven by negative reinforcement mechanisms) remains unclear. This study investigated neural functioning of expectancy and receipt for gains and losses in adults with (METH+) and without (METH-) histories of methamphetamine dependence.Participants (17 METH+; 23 METH-) performed a probabilistic feedback expectancy task during blood-oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). Participants were given visual cues probabilistically associated with monetary gain, loss, or neutral outcomes. General linear models examined the BOLD response to: (1) anticipation of gains and losses, and (2) gain and loss monetary outcomes.METH+ had less BOLD response to loss anticipation than METH- in the ventral striatum and posterior caudate. METH+ also showed more BOLD response to loss outcomes than to gain outcomes in the anterior and posterior caudate, whereas METH- did not show differential responses to the valence of outcomes.METH+ individuals showed attenuated neural response to anticipated gains and losses, but their response to loss outcomes was greater than to gain outcomes. A decreased response to loss anticipation, along with a greater response to loss outcomes, suggests an altered ability to evaluate future risks and benefits based upon prior experience, which may underlie suboptimal decision-making in METH+ individuals that increases the likelihood of risky behavior.
| S-EPMC5225125 | biostudies-other