The role of the GABA system in amphetamine-type stimulant use disorders.
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ABSTRACT:
SUBMITTER: Jiao D
PROVIDER: S-EPMC4419710 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
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The role of the GABA system in amphetamine-type stimulant use disorders.
Jiao Dongliang D Liu Yao Y Li Xiaohong X Liu Jinggen J Zhao Min M
Frontiers in cellular neuroscience 20150505
Abuse of amphetamine-type stimulants (ATS) has become a global public health problem. ATS causes severe neurotoxicity, which could lead to addiction and could induce psychotic disorders or cognitive dysfunctions. However, until now, there has been a lack of effective medicines for treating ATS-related problems. Findings from recent studies indicate that in addition to the traditional dopamine-ergic system, the GABA (gamma-aminobutyric acid)-ergic system plays an important role in ATS abuse. Howe ...[more]
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Project description:Introduction: Amphetamine-type stimulants (ATS) use is a global concern due to increased usage and the harm to physical, mental, and social well-being. The objective of this overview of systematic reviews is to summarise trial results of psychosocial interventions and describe their efficacy and safety. Methods: We searched seven bibliographic databases to November 2020 for systematic reviews examining ATS misuse treatment by psychosocial interventions. Given the apparent incompleteness of the included reviews, we undertook a supplemental meta-analysis of all eligible primary studies. Results: We included 11 systematic reviews of moderate to high quality and 39 primary studies which assessed the outcomes of psychosocial interventions on people who use ATS. The key findings include: (1) There were conflicting results about the effectiveness of psychosocial interventions among reviews, which may confuse decision-makers in selecting treatment. (2) In the supplemental meta-analysis, relative to usual care (only counselling or self-help materials), membership of a psychological intervention group was associated with an important reduction in drug usage [risk ratio (RR) 0.80, 95% CI: 0.75 to 0.85]. Patients in psychological interventions used injectables substantially less [odds ratio (OR) 0.35, 95% CI: 0.24 to 0.49]. The risk of unsafe sex in the psychosocial intervention group was lower than in the control group (RR 0.49, 95% CI: 0.34 to 0.71). The combination of therapies reduced 1.51 day using drugs in the preceding 30 days (95% CI: -2.36 to -0.67) compared to cognitive behavioural therapy intervention alone. (3) Compared to usual care, cognitive behavioural therapy was less likely to be retained at follow-up (RR 0.89, 95% CI: 0.82 to 0.97; high-quality evidence). However, the additional of contingency management strategy can make an important improvement upon retention (RR 1.42, 95%CI: 1.25 to 1.62). Authors' Conclusions: Integrated models are more effective than a single-treatment strategy. Comprehensive and sustained psychosocial interventions can help to reduce use of ATS and other drugs, risk behaviours and mental disorders, and significantly improve treatment adherence.
| S-EPMC8245759 | biostudies-literature
Project description:IntroductionAmphetamine type stimulant (ATS) use and self-harm are both major public health concerns globally. Use of ATS is associated with a range of health and social problems, and has been increasing internationally in the last decade. Self-harm and ATS use share a number of underlying risk factors and occur at elevated rates in marginalised groups with high rates of exposure to trauma. The relationship between self-harm and ATS use is likely complex, and the causal pathway may run in either direction. A comprehensive review, synthesis and analysis of the evidence are warranted to investigate this relationship and inform policy and practice.Methods and analysisWe will search the Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO and Scopus databases for relevant observational studies published in peer-reviewed journals. The initial search was conducted on 5 February 2021, with a final search expected on 1 February 2022. All studies will be independently screened by two reviewers, first on title and abstract, and then on full-text to determine inclusion in the review. We place no restriction on the population that studies investigate, our exposure of interest is both prescription and illicit ATS use, comparators will be those not currently using ATS, and our primary outcome of interest is the prevalence of self-harm. Data will be extracted using a predesigned template, and pooled prevalence and pooled measures of effect for the association between ATS use and self-harm. If sufficient data are available, we will perform multiple meta-analyses to produce pooled measures of effect for each measure of ATS exposure, as well as different population sub-groups. The Methodological Standard for Epidemiological Research scale will be used to assess study quality, and Egger's test and I2 values will be used to assess publication bias and heterogeneity, respectively.Ethics and disseminationNo ethical approval is required for this review. We will only synthesise information from published studies that were conducted with ethical approval, so no individual participant data will be used. We will disseminate our findings via publication in a peer-reviewed journal, national and international conference presentations, and presentations to stakeholders in the community.Trial registration numberThis study has been registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42021226562).
| S-EPMC8788311 | biostudies-literature
Project description:BackgroundAmphetamine-type stimulants (ATS) refer to a group of synthetic stimulants including amphetamine, methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA) and related substances. ATS are highly addictive and prolonged use may result in a series of mental and physical symptoms including anxiety, confusion, insomnia, mood disturbances, cognitive impairments, paranoia, hallucinations and delusion.Currently there is no widely accepted treatment for ATS-use disorder. However, cognitive-behavioural treatment (CBT) is the first-choice treatment. The effectiveness of CBT for other substance-use disorders (e.g. alcohol-, opioid- and cocaine-use disorders) has been well documented and as such this basic treatment approach has been applied to the ATS-use disorder.ObjectivesTo investigate the efficacy of cognitive-behavioural treatment for people with ATS-use disorder for reducing ATS use compared to other types of psychotherapy, pharmacotherapy, 12-step facilitation, no intervention or treatment as usual.Search methodsWe identified randomised controlled trials (RCT) and quasi-RCTs comparing CBT for ATS-use disorders with other types of psychotherapy, pharmacotherapy, 12 step facilitation or no intervention. We searched the Cochrane Drugs and Alcohol Group Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE via PubMed, Embase and five other databases up to July 2018. In addition, we examined reference lists of eligible studies and other systematic reviews. We contacted experts in the field.Selection criteriaEligibility criteria consisted of RCTs and quasi-RCTs comparing CBT versus other types of interventions with adult ATS users (aged 18 years or older) diagnosed by any explicit diagnostic system. Primary outcomes included abstinence rate and other indicators of drug-using behaviours.Data collection and analysisWe used standard methodological procedures expected by Cochrane.Main resultsOnly two studies met the eligibility criteria. Both studies were at low risk of selection bias and reporting bias. In one study, almost half of participants in the intervention group dropped out and this study was at high risk of attrition bias. The studies compared a single session of brief CBT or a web-based CBT to a waiting-list control (total sample size across studies of 129). Results were mixed across the studies. For the single-session brief CBT study, two out of five measures of drug use produced significant results, percentage of abstinent days in 90 days (odds ratio (OR) 0.22, 95% confidence interval (CI) 0.02 to 2.11) and dependence symptoms (standardised mean difference (SMD) -0.59, 95% CI-1.16 to-0.02). Little confidence could be placed in the results from this study give the small sample size (25 participants per group) and corresponding large CIs around the observed effects. For the web-based CBT, there was no significant difference across different outcomes. Neither study reported adverse effects. The meta-analytic mean across these two trials for drug use was not significant (SMD -0.28, 95% CI-0.69 to 0.14). In summary, overall quality of evidence was low and there was insufficient evidence to conclude that CBT is effective, or ineffective, at treating ATS use.Authors' conclusionsCurrently, there is not enough evidence to establish the efficacy of CBT for ATS-use disorders because of a paucity of high-quality research in this area.
| S-EPMC8356519 | biostudies-literature
Project description:Qualitative poor decision-making and associated altered neuronal activation patterns have been described for the users of several drugs, amongst others for stimulants like amphetamine and MDMA. Deficits in decision-making might be caused by an augmented attraction to short-term rewarding properties despite negative long-term consequences, leading to rigid stimulus-response patterns. In the present imaging study, we investigated decision-making and associated neuronal activation in three groups differing in their exposure to amphetamine and MDMA. An established paradigm on risky choices was used to evaluate decision-making performance and corresponding functional magnet resonance imaging (fMRI) activation. Subjects could choose between a low-risk control gamble and an experimental gamble, which always differed in the probability of winning or losing, as well as the magnitudes of monetary gain or loss. Experienced users (EU), users with low exposure to stimulants and drug-naive controls, did not differ from each other in behavioral performance. In accordance with our hypotheses, the anticipation of reward led to an activation of primarily the frontal cortex and the striatum in low-exposure users and drug-naive controls. In contrast, frontal and parietal activation was observed in all groups when the actual outcome of an experimental gamble was presented. EU displayed more activation compared to both control groups when there was a high probability of winning. The study at hand supports the hypothesis that neuronal activation patterns might even differ between drug users and healthy controls when no behavioral deficits are apparent. In EU, the probability of the occurrence of an event has more influence on neuronal activation than on the actual magnitude of reinforcing properties of this event.
| S-EPMC3682139 | biostudies-other
Project description:BACKGROUND:Amphetamine type stimulants (ATS) use is highly prevalent and frequently co-occurs with opioid dependence in Malaysia and Asian countries. No medications have established efficacy for treating ATS use disorder. This study evaluated the safety, tolerability, and potential efficacy of atomoxetine for treating ATS use disorder. METHODS:Participants with opioid and ATS dependence (N?=?69) were enrolled in a pilot, double-blind, placebo-controlled randomized clinical trial; all received buprenorphine/naloxone and behavioral counseling and were randomized to atomoxetine 80?mg daily (n?=?33) or placebo (n?=?33). The effect size of the between-group difference on the primary outcome, proportion of ATS-negative urine tests, was estimated using Cohen's d for the intention-to-treat (ITT) sample and for higher adherence subsample (?60?days of atomoxetine or placebo ingestion). RESULTS:Participants were all male with mean (SD) age 39.4 (6.8) years. The proportion of ATS-negative urine tests was higher in atomoxetine- compared to placebo-treated participants: 0.77 (0.63-0.91) vs. 0.67 (0.53-0.81, d?=?0.26) in the ITT sample and 0.90 (0.75-1.00) vs. 0.64 (0.51-0.78, d?=?0.56) in the higher adherence subsample. The proportion of days abstinent from ATS increased from baseline in both groups (p?<?0.001) and did not differ significantly between atomoxetine- and placebo-treated participants (p?=?0.42). Depressive symptoms were reduced from baseline in both groups (p?<?0.02) with a greater reduction for atomoxetine- than placebo-treated participants (p?<?0.02). There were no serious adverse events or adverse events leading to medication discontinuation. CONCLUSIONS:The findings support clinical tolerability and safety and suggest potential efficacy of atomoxetine for treating ATS use disorder in this population.
| S-EPMC5911201 | biostudies-literature
Project description:BackgroundEmerging data indicate a resurgence of availability and harms of amphetamine-type stimulant (ATS) use. This study examined ATS overdose-involved emergency department (ED) visit trends and visit characteristics associated with ATS overdose.MethodsData from the Healthcare Cost and Utilization Project's (HCUP) 2010-2017 Nationwide Emergency Department Sample identified ATS overdose-involved visits. Predicted trend lines from 2010 to 2015 were fit using weighted logistic regression forany or only ATS-involved overdose using ICD-9-CM discharge diagnosis codes; percentage change from 2016 to 2017 used ICD-10-CM. Multivariable logistic regression examined characteristics in 2017 associated with only ATS-involved overdoses compared to drug overdoses not involving ATS.ResultsEvery year from 2010 to 2015 the odds of any ATS overdose-involved ED visits increased 11 % (odds ratio [OR]: 1.11, 95 % CI: 1.09, 1.14) and 7 % for only ATS overdose-involved visits (OR: 1.07, 95 % CI: 1.04, 1.10). From 2016 to 2017, any and only ATS overdose-involved visit rates increased 19.1 % and 20.5 %, respectively (P < .05). In 2017, ATS overdose-involved visits (N = 42,428) accounted for 4.4 % of all drug overdose visits (N = 956,266). In adjusted regression models, characteristics more prevalent among patients with only ATS overdose included Western region; micropolitan and noncore urbanization levels; unintentional, undetermined, and assault intents; and cardiovascular effects.ConclusionsOur findings, coupled with the rising availability of ATS and related harms, underscore the expansion of current substance use and overdose prevention and response efforts to address stimulant use, particularly among groups at risk. Research to identify additional individual and community-level risk factors for increasing ATS overdose is warranted.
| S-EPMC7606828 | biostudies-literature
Project description:Some schizophrenia patients are more sensitive to amphetamine (AMPH)-induced exacerbations in psychosis-an effect that correlates with higher striatal dopamine release. This enhanced vulnerability may be related to gamma-aminobutyric acid (GABA) deficits observed in schizophrenia. We hypothesized that a pharmacologically induced GABA deficit would create vulnerability to the psychotomimetic effects to the 'subthreshold' dose of AMPH in healthy subjects, which by itself would not induce clinically significant increase in positive symptoms. To test this hypothesis, a GABA deficit was induced by intravenous infusion of iomazenil (IOM; 3.7??g/kg), an antagonist and partial inverse agonist of benzodiazepine receptor. A subthreshold dose of AMPH (0.1?mg/kg) was administered by intravenous infusion. Healthy subjects received placebo IOM followed by placebo AMPH, active IOM followed by placebo AMPH, placebo IOM followed by active AMPH, and active IOM followed by active AMPH in a randomized, double-blind crossover design over 4 test days. Twelve healthy subjects who had a subclinical response to active AMPH alone were included in the analysis. Psychotomimetic effects (Positive and Negative Syndrome Scale (PANSS)), perceptual alterations (Clinician Administered Dissociative Symptoms Scale (CADSS)), and subjective effects (visual analog scale) were captured before and after the administration of drugs. IOM significantly augmented AMPH-induced peak changes in PANSS positive symptom subscale and both subjective and objective CADSS scores. There were no pharmacokinetic interactions. In conclusion, GABA deficits increased vulnerability to amphetamine-induced psychosis-relevant effects in healthy subjects, suggesting that pre-existing GABA deficits may explain why a subgroup of schizophrenia patients are vulnerable to AMPH.
| S-EPMC4864658 | biostudies-literature
Project description:BACKGROUND:The growing abuse of amphetamine-type stimulants leads to new challenges to human health. A possible addiction mechanism has been proposed by altered functional architecture of the nucleus accumbens (NAc) during resting state. NAc contains different subdivisions and they may play different roles in addiction. The aim of the present study was to examine whether there are common or distinct patterns of functional connectivity of the NAc subdivisions in amphetamine-type stimulant abusers (ATSAs). METHODS:The present study recruited 17 male ATSAs and 22 healthy male controls. All the subjects underwent resting-state functional magnetic resonance imaging (fMRI) with their eyes closed. The NAc was divided into core-like and shell-like subdivisions. We used seed-based resting-state functional connectivity (RSFC) analyses to identify differences in brain functional architecture between ATSAs and healthy controls (HCs). RESULTS:ATSAs had lower positive RSFCs with all of the NAc subdivisions over the left orbital part of superior frontal gyrus and higher positive RSFCs with the NAc subdivisions over the left opercular part of inferior frontal gyrus than HCs, which indicates common abnormalities across the NAc subdivisions in ATSAs. In addition, the RSFCs between the NAc subdivisions and the left orbital part of superior frontal gyrus were negatively correlated with the addiction severity in ATSAs. CONCLUSION:These results provide evidence that there are common RSFC patterns of the NAc subdivisions in ATSAs. The abnormality indicated by disrupted functional connectivity between the NAc subdivisions and prefrontal cortex suggests abnormal interaction between the rewarding process and cognitive control in ATSAs. Our results shed insight on the neurobiological mechanisms of ATSA and suggest potential novel therapeutic targets for treatment and intervention of ATSAs.
| S-EPMC6937793 | biostudies-literature
Project description:BackgroundStimulant (cocaine and/or methamphetamine) use has increased among people with opioid use disorder. We conducted a systematic review of medications for stimulant use disorders in this population.MethodsWe searched for randomized controlled trials in multiple databases through April 2019, and dual-screened studies using pre-specified inclusion criteria. Primary outcomes were abstinence defined as stimulant-negative urine screens for ≥3 consecutive weeks; overall use as the proportion of stimulant-negative urine specimens; and retention as the proportion of participants who completed treatment. We rated strength of evidence using established criteria and conducted meta-analyses of comparable interventions and outcomes.ResultsThirty-four trials of 22 medications focused on cocaine use disorder in patients with opioid use disorder. Most studies enrolled participants stabilized on opioid maintenence therapy, generally methadone. None of the six studies that assessed abstinence found significant differences between groups. We found moderate-strength evidence that antidepressants (desipramine, bupropion, and fluoxetine) worsened retention. There was moderate-strength evidence that disulfiram worsened treatment retention (N = 605, RR 0.86, 95 % CI 0.77 to 0.95). We found low-strength evidence that psychostimulants (mazindol and dexamphetamine) may reduce cocaine use, though the difference was not statistically significant (standard mean difference 0.35 [95 % CI -0.05 to 0.74]). There was only 1 trial for methamphetamine use disorder, which showed insufficient-strength evidence for naltrexone.ConclusionsCo-occurring stimulant/opioid use disorder is an important problem for targeting future research. Medication trials for methamphetamine use disorder are lacking in this population. Most of the medications studied for cocaine use were ineffective, although psychostimulants warrant further study.
| S-EPMC8562993 | biostudies-literature
Project description:There is ample evidence that genetic factors play an important role in anxiety disorders. In support, human genome-wide association studies have implicated several novel candidate genes. However, illumination of such genetic factors involved in anxiety disorders has not resulted in novel drugs over the past decades. A complicating factor is the heterogeneous classification of anxiety disorders in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) and diverging operationalization of anxiety used in preclinical and clinical studies. Currently, there is an increasing focus on the gene × environment (G × E) interaction in anxiety as genes do not operate in isolation and environmental factors have been found to significantly contribute to the development of anxiety disorders in at-risk individuals. Nevertheless, extensive research on G × E mechanisms in anxiety has not resulted in major breakthroughs in drug discovery. Modification of individual genes in rodent models has enabled the specific study of anxiety in preclinical studies. In this context, two extensively studied neurotransmitters involved in anxiety are the gamma-aminobutyric acid (GABA) and 5-HT (5-hydroxytryptamine) system. In this review, we illustrate the complex interplay between genes and environment in anxiety processes by reviewing preclinical and clinical studies on the serotonin transporter (5-HTT), 5-HT1A receptor, 5-HT2 receptor, and GABAA receptor. Even though targets from the serotonin and GABA system have yielded drugs with known anxiolytic efficacy, the relation between the genetic background of these targets and anxiety symptoms and development of anxiety disorders is largely unknown. The aim of this review is to show the vast complexity of genetic and environmental factors in anxiety disorders. In light of the difficulty with which common genetic variants are identified in anxiety disorders, animal models with translational validity may aid in elucidating the neurobiological background of these genes and their possible role in anxiety. We argue that, in addition to human genetic studies, translational models are essential to map anxiety-related genes and to enhance our understanding of anxiety disorders in order to develop potentially novel treatment strategies.
| S-EPMC3677985 | biostudies-literature