Dataset Information

Association of Stimulant Use With Dopaminergic Alterations in Users of Cocaine, Amphetamine, or Methamphetamine: A Systematic Review and Meta-analysis.

ABSTRACT: Importance:Stimulant use disorder is common, affecting between 0.3% and 1.1% of the population, and costs more than $85 billion per year globally. There are no licensed treatments to date. Several lines of evidence implicate the dopamine system in the pathogenesis of substance use disorder. Therefore, understanding the nature of dopamine dysfunction seen in stimulant users has the potential to aid the development of new therapeutics. Objective:To comprehensively review the in vivo imaging evidence for dopaminergic alterations in stimulant (cocaine, amphetamine, or methamphetamine) abuse or dependence. Data Sources:The entire PubMed, EMBASE, and PsycINFO databases were searched for studies from inception date to May 14, 2016. Study Selection:Case-control studies were identified that compared dopaminergic measures between stimulant users and healthy controls using positron emission tomography or single-photon emission computed tomography to measure striatal dopamine synthesis or release or to assess dopamine transporter availability or dopamine receptor availability. Data Extraction and Synthesis:Demographic, clinical, and imaging measures were extracted from each study, and meta-analyses and sensitivity analyses were conducted for stimulants combined, as well as for cocaine and for amphetamine and methamphetamine separately if there were sufficient studies. Main Outcomes and Measures:Differences were measured in dopamine release (assessed using change in the D2/D3 receptor availability after administration of amphetamine or methylphenidate), dopamine transporter availability, and dopamine receptor availability in cocaine users, amphetamine and methamphetamine users, and healthy controls. Results:A total of 31 studies that compared dopaminergic measures between 519 stimulant users and 512 healthy controls were included in the final analysis. In most of the studies, the duration of abstinence varied from 5 days to 3 weeks. There was a significant decrease in striatal dopamine release in stimulant users compared with healthy controls: the effect size was -0.84 (95% CI, -1.08 to -0.60; P?

SUBMITTER: Ashok AH

PROVIDER: S-EPMC5419581 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Association of Stimulant Use With Dopaminergic Alterations in Users of Cocaine, Amphetamine, or Methamphetamine: A Systematic Review and Meta-analysis.

Ashok Abhishekh H AH Mizuno Yuya Y Volkow Nora D ND Howes Oliver D OD

JAMA psychiatry 20170501 5

<h4>Importance</h4>Stimulant use disorder is common, affecting between 0.3% and 1.1% of the population, and costs more than $85 billion per year globally. There are no licensed treatments to date. Several lines of evidence implicate the dopamine system in the pathogenesis of substance use disorder. Therefore, understanding the nature of dopamine dysfunction seen in stimulant users has the potential to aid the development of new therapeutics.<h4>Objective</h4>To comprehensively review the in vivo ...[more]

PMID: 28297025

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Project description:Dopamine system plays a pivotal role in specific kinds of substance use disorders (SUD, i. e., cocaine and methamphetamine use disorders). Many studies addressed whether dopamine-involved craving could be alleviated by non-invasive brain stimulation (NIBS) techniques. Nevertheless, the outcomes were highly inconsistent and the stimulating parameters were highly variable. In the current study, we ran a meta-analysis to identify an overall effect size of NIBS and try to find stimulating parameters of special note. We primarily find 2,530 unduplicated studies in PubMed, Psychology and Behavioral Sciences Collection, PsycARTICLES, PsycINFO, and Google Scholar database involving "Cocaine"/"Amphetamine"/"Methamphetamine" binded with "TMS"/"tDCS"/"non-invasive stimulation" in either field. After visual screening, 26 studies remained. While 16 studies were further excluded due to the lack of data, invalid craving scoring or the absence of sham condition. At last, 16 units of analysis in 12 eligible studies were coded and forwarded to a random-effect analysis. The results showed a large positive main effect of stimulation (Hedge's g = 1.116, CI = [0.597, 1.634]). Further subgroup analysis found that only high-frequency repetitive transcranial magnetic stimulation (rTMS) could elicit a significant decrease in craving, while the outcome of low-frequency stimulation was relatively controversial. Moreover, univariate meta regression revealed that the number of pulses per session could impose negative moderation toward the intervention. No significant moderation effect was found in types of abuse, overall days of stimulation and other variables of stimulating protocol. In conclusion, this meta-analysis offered a persuasive evidence for the feasibility of using NIBS to remit substance addictive behavior directly based on dopamine system. We also give clear methodological guidance that researchers are expected to use high-frequency, sufficiently segmented rTMS to improve the efficacy in future treatments.

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.

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).

Project description:BACKGROUND:Polydrug use may challenge effective treatment for substance use disorders. We evaluate whether secondary substance use modifies the association between treatment and primary drug use among primary heroin, cocaine and methamphetamine (MA) users. METHODS:Data were obtained from prospective cohort studies on people who use illicit drugs (PWUD) in California, USA. Using repeated monthly data on self-reported secondary substance use (heroin, cocaine, MA, alcohol or marijuana; ?1day in a month), primary drug use (?1day in a month), and treatment participation, collected via timeline follow-back, we fitted generalized linear mixed multiple regression models controlling for potential confounders to examine the interactions between treatment and secondary substance use on the odds of primary heroin, cocaine and MA use, respectively. RESULTS:Included in our study were 587 primary heroin, 444 primary MA, and 501 primary cocaine users, with a median of 32.4, 13.3 and 18.9 years of follow-up, respectively. In the absence of secondary substance use, treatment was strongly associated with decreased odds of primary drug use (adjusted odds ratios (aORs): 0.25, 95% CI: 0.24, 0.27, 0.07 (0.06, 0.08), and 0.07 (0.07, 0.09)) for primary heroin, MA, and cocaine users, respectively. Secondary substance use of any kind moderated these associations (0.82 (0.78, 0.87), 0.25 (0.21, 0.30) and 0.53 (0.45, 0.61), respectively), and these findings were consistent for each type of secondary substance considered. Moreover, we observed different associations in terms of direction and magnitude between secondary substance use and primary drug use during off-treatment periods across substance types. CONCLUSION:This study demonstrates secondary substance use moderates the temporal associations between treatment and primary drug use among primary heroin, MA and cocaine users. Disparate patterns of polydrug use require careful measurement and analysis to inform targeted treatment for polydrug users.

Project description:BackgroundStimulant drugs are second only to cannabis as the most widely used class of illicit drug globally, accounting for 68 million past-year consumers. Dependence on amphetamines (AMPH) or methamphetamine (MA) is a growing global concern. Yet, there is no established pharmacotherapy for AMPH/MA dependence. A comprehensive assessment of the research literature on pharmacotherapy for AMPH/MA dependence may inform treatment guidelines and future research directions.MethodsWe systematically reviewed the peer-reviewed literature via the electronic databases PubMed, EMBASE, CINAHL and SCOPUS for randomised controlled trials reported in the English language examining a pharmacological treatment for AMPH/MA dependence or use disorder. We included all studies published to 19 June 2019. The selected studies were evaluated for design; methodology; inclusion and exclusion criteria; sample size; pharmacological and (if included) psychosocial interventions; length of follow-up and follow-up schedules; outcome variables and measures; results; overall conclusions and risk of bias. Outcome measures were any reported impact of treatment related to AMPH/MA use.ResultsOur search returned 43 studies that met our criteria, collectively enrolling 4065 participants and reporting on 23 individual pharmacotherapies, alone or in combination. Disparate outcomes and measures (n = 55 for the primary outcomes) across studies did not allow for meta-analyses. Some studies demonstrated mixed or weak positive signals (often in defined populations, e.g. men who have sex with men), with some variation in efficacy signals dependent on baseline frequency of AMPH/MA use. The most consistent positive findings have been demonstrated with stimulant agonist treatment (dexamphetamine and methylphenidate), naltrexone and topiramate. Less consistent benefits have been shown with the antidepressants bupropion and mirtazapine, the glutamatergic agent riluzole and the corticotropin releasing factor (CRF-1) antagonist pexacerfont; whilst in general, antidepressant medications (e.g. selective serotonin reuptake inhibitors [SSRIs], tricyclic antidepressants [TCAs]) have not been effective in reducing AMPH/MA use.ConclusionsNo pharmacotherapy yielded convincing results for the treatment of AMPH/MA dependence; mostly studies were underpowered and had low treatment completion rates. However, there were positive signals from several agents that warrant further investigation in larger scale studies; agonist therapies show promise. Common outcome measures should include change in use days. Future research must address the heterogeneity of AMPH/MA dependence (e.g. coexisting conditions, severity of disorder, differences between MA and AMPH dependence) and the role of psychosocial intervention.

Dataset Information

Association of Stimulant Use With Dopaminergic Alterations in Users of Cocaine, Amphetamine, or Methamphetamine: A Systematic Review and Meta-analysis.

Publications

Association of Stimulant Use With Dopaminergic Alterations in Users of Cocaine, Amphetamine, or Methamphetamine: A Systematic Review and Meta-analysis.

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