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Aims Design, setting and participants Interventions Measurements Findings Conclusions This study tested the efficacy and safety of a 12‐week course of lisdexamfetamine in reducing methamphetamine use, an outcome which is associated with improvements in health and wellbeing, in people dependent on methamphetamine.This study was a randomised double‐blind placebo‐controlled trial conducted in six specialist outpatient clinics in Adelaide, Melbourne, Newcastle and Sydney, Australia (2018–2021). Participants were164 adults with methamphetamine dependence, reporting at least 14 use days out of the previous 28 days (62% male, 38% female, < 1% other; mean age 39 years).Participants were randomly allocated 1:1 to a 15‐week regimen of lisdexamfetamine (1‐week induction to 250 mg, 12‐week maintenance regimen, 2‐week reduction; n = 80) or matched placebo (n = 84), followed‐up to Week 19.The primary efficacy measure was past 28‐day methamphetamine use at Week 13. Safety was assessed by adverse event rates. Secondary measures included methamphetamine use during the 12‐week treatment period and treatment satisfaction.Nine randomized participants did not start treatment (five were allocated to lisdexamfetamine and four allocated to placebo) and were excluded from the analyses. Fifty‐seven per cent of participants were retained on study medication to primary end‐point. There was only weak evidence of a lisdexamfetamine benefit at 13 weeks [adjusted difference in days of methamphetamine use = 2.2, 95% confidence interval (CI) = –0.5 to 5.0; P = 0.49]. However, throughout the whole 12‐week treatment maintenance phase, the lisdexamfetamine group had fewer days of methamphetamine use in total (difference = 8.8, 95% CI = 2.7–15.0; P = 0.005). The lisdexamfetamine group reported greater self‐reported treatment effectiveness [odds ratio (OR) = 2.89, 95% CI = 1.67–5.02; P < 0.001] and treatment satisfaction (OR = 3.80, 95% CI = 1.93–7.47; P < 0.001). Adverse events with lisdexamfetamine included nausea. Serious adverse events occurred in four (5%) of participants who received lisdexamfetamine.Lisdexamfetamine appears to reduce methamphetamine use over a 12‐week treatment period, although there is only weak evidence that reduced use is maintained during the last 4 weeks. [ABSTRACT FROM AUTHOR]

Background: The quinone oxidoreductase 1 (NQO1) gene was involved in the pathophysiological process of illicit drugs abuse, and its polymorphisms might be associated with methamphetamine (METH) dependence susceptibility. The purpose of this study was to examine the NQO1 mRNA and protein levels and to analyze the 609C/T polymorphism (rs1800566) between METH‐dependent patients and controls. Methods: A total of 392 METH‐dependent patients (cases) and 669 healthy controls (controls) were enrolled in the study. The quantitative real‐time polymerase chain reaction (RT‐qPCR) and enzyme‐linked immunosorbent assay (ELISA) were used to detect the relative expressions of NQO1 mRNA in PBMCs and protein levels in plasma, respectively. PCR‐restriction fragment length polymorphism (RFLP‐PCR) and direct‐sequencing genotyping were used to detect the alleles and genotypes of NQO1 609C/T polymorphism. Results: The levels of NQO1 mRNA in cases (3.2650 ± 2.2943) was significantly higher than in controls (1.0125 ± 0.7959) (p < 0.001), the plasma protein in cases (0.2368 ± 0.1486) was significantly lower than in controls (0.5844 ± 0.1742) (p < 0.001). The T allele of the 609C/T polymorphism significantly increased the risk of METH dependence (p = 0.032, OR = 1.214, 95%CI = 1.017–1.450). The TC and TC/TT genotypes of 609C/T were observed significantly more frequently in cases than in controls, respectively (TC vs CC: p = 0.012, OR = 1.457, 95% CI = 1.087–1.952; TC/TT vs CC: p = 0.008, OR = 1.460, 95% CI = 1.102–1.935). Similar results were obtained after adjusting for age and sex. We failed to find that any genotype of 609C/T polymorphism affected the mRNA or plasma protein levels in controls, respectively (p > 0.05). Conclusion: The findings suggested that NQO1 might play an important role in the pathophysiological process of METH dependence, and the 609C/T polymorphism might contribute to the susceptibility to METH dependence in a Chinese Han population. [ABSTRACT FROM AUTHOR]

Aims: Pharmacotherapy for methamphetamine dependence has not yet been developed in Japan or elsewhere in the world. Ifenprodil is a blocker of G protein‐activated inwardly rectifying potassium channels that play a key role in the mechanism of action of addictive substances. Our aim is to examine the safety, efficacy, and outcomes of ifenprodil for the treatment of methamphetamine dependence in a randomized, double‐blind, placebo‐controlled trial. Methods: The recruitment of outpatients with methamphetamine dependence began in January 2018. The patients will be randomized into three arms: placebo, 60 mg/d ifenprodil, or 120 mg/d ifenprodil. Placebo or ifenprodil will be taken for 84 days. We will use Cerocral fine granule 4%® (ifenprodil tartrate). Follow‐up assessments will be conducted for 84 d after the drug administration period. All of the patients will be assessed by self‐administered questionnaires and urine tests. The primary outcome will be the presence or absence of methamphetamine use during the 84‐day administration period in the 120 mg/d ifenprodil and placebo groups. Secondary outcomes will include the number of days and percentage of days of abstinence from methamphetamine use, positive urine for methamphetamine, relapse risk, and drug craving. Discussion: This study is the first clinical trial of ifenprodil treatment for methamphetamine dependence and is designed as an intervention test with off‐label drug use. The present study is expected to provide evidence of the effects of ifenprodil treatment on methamphetamine dependence. Trial registry: This trial was registered in the UMIN clinical trial registry (UMIN000030849; date of registration: January 17, 2018). [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: Methamphetamine dependence is associated with heightened impulsivity and diminished quality of life, but the link between impulsivity and changes in quality of life during treatment has not been examined. We aimed to investigate how different elements of impulsivity predict change in quality of life in the 6 weeks after engaging in treatment. Design: Longitudinal, observational cohort study. Setting: Public and private detoxification and rehabilitation facilities in metropolitan Melbourne, Australia. Participants: One hundred and eight individuals with methamphetamine dependence (81 male) tested within 3 weeks of commencing treatment; 80 (74%) were followed‐up at 6 weeks. Measurements: The Continuous Performance Test‐2 measured impulsive action (cognitive and motor impulsivity); the Delay Discounting Task measured impulsive choice. Quality of life was measured with the World Health Organization Quality of Life Scale—Brief, which includes social, psychological, physical and environment domains. Control variables included age, gender, estimated IQ, depression severity score, methamphetamine dependence severity score, cannabis dependence severity score and treatment modality. Findings: We found that all three forms of impulsivity were significant predictors of change in the social domain: motor impulsivity (β = −0.54, P = 0.013), cognitive impulsivity (β = −0.46, P = 0.029) and impulsive choice (β = −0.26, P = 0.019). Change in the psychological domain was predicted significantly by motor impulsivity (β = −0.45, P = 0.046). Control variables of age and depression were associated significantly with changes in the physical domain. Conclusions: In Australian methamphetamine‐dependent individuals, elevated impulsivity predicts lower improvement of social and psychological quality of life in the first 6–9 weeks of treatment. [ABSTRACT FROM AUTHOR]

To compare the effects of heroin and methamphetamine (METH) addiction on dopamine transporters (DATs) in the same dose and duration, we assessed DAT levels in the striatum by 99m Tc-TRODAT-1 single-photon emission computed tomography (SPECT) brain images in people with heroin and METH dependence. We recruited 21 healthy human controls, 23 heroin-dependent subjects and 25 METH abusers. The heroin- and METH-dependent subjects exhibited negative urine toxicology after undergoing physiological detoxification. All subjects underwent SPECT brain imaging, and specific tracer uptake ratios (SURs) were assessed bilaterally in the regions of interest. A significant SUR reduction in heroin-dependent subjects and METH-dependent subjects compared with healthy controls was found in the left striatum, right striatum, left caudate nucleus, right caudate nucleus, left putamen and right putamen. There were no significant differences in the heroin group and METH group for the left striatum, right striatum, left caudate nucleus, right caudate nucleus, left putamen and right putamen. The scores of craving, HAMA (Hamilton Anxiety Rating Scale), in heroin abusers were lower than in the METH abusers. Our results show that people with heroin and METH dependence who are currently abstinent had lower DAT levels in the striatum than healthy controls. There were no differences in striatal DAT in heroin and METH users. These results suggest that chronic heroin and METH abuse appears to produce similar effects in striatal DAT in humans. METH users may have more serious craving and anxiety symptoms than heroin users with prolonged abstinence. [ABSTRACT FROM AUTHOR]

To date, no medication has been approved as an effective treatment for methamphetamine dependence. Topiramate has attracted considerable attention as a treatment for the dependence on alcohol and stimulants. Therefore, this study aimed to evaluate the effect of topiramate for methamphetamine dependence. This study was a double-blind, randomized, placebo-controlled trial. In the present investigation, 62 methamphetamine-dependent adults were enrolled and randomized into two groups, and received topiramate or a placebo for 10 weeks in escalating doses from 50 mg/day to the target maintenance dose of 200 mg/day. Addiction severity index ( ASI) and craving scores were registered every week. The Beck questionnaire was also given to each participant at baseline and every 2 weeks during the treatment. Urine samples were collected at baseline and every 2 weeks during the treatment. Fifty-seven patients completed 10 weeks of the trial. There was no significant difference between both groups in the mean percentage of prescribed capsules taken by the participants. At week six, the topiramate group showed a significantly lower proportion of methamphetamine-positive urine tests in comparison with the placebo group ( P = 0.01). In addition, there were significantly lower scores in the topiramate group in comparison with the placebo group in two domains of ASI: drug use severity ( P < 0.001) and drug need ( P < 0.001). Furthermore, the craving score (duration) significantly declined in the topiramate patients compared to those receiving the placebo. In conclusion, the results of this trial suggest that topiramate may be beneficial for the treatment of methamphetamine dependence. [ABSTRACT FROM AUTHOR]

Introduction and Aims. Cigarette smoking occurs frequently among individuals with methamphetamine (MA) dependence. Preclinical and clinical evidence has suggested that the common co-abuse of MA and cigarettes represents a pharmacologically meaningful pattern. Methods. The present study is a secondary analysis of a randomised, placebo-controlled trial of bupropion treatment for MA dependence (bupropion n = 36; placebo n = 37). A hierarchical logistic modelling approach assessed the efficacy of bupropion for reducing MA use separately among smokers and non-smokers. Among smokers, relations between cigarettes smoked and MA use were assessed. Results. Smoking status did not affect treatment responsiveness in either the bupropion condition or the placebo condition. In the placebo condition, increased cigarette use was associated with an increased probability of MA use during the same time period. This effect was not observed in the bupropion condition. Discussion and Conclusions. Initial smoking status did not impact treatment outcomes. Among smokers, results suggest that bupropion may dissociate cigarette and MA use. The effect was modest and a precise pharmacological mechanism remains elusive. Cholinergic systems may be relevant for MA use outcomes. Future studies should continue to assess the role of smoking in MA treatment outcomes.[Brensilver M, Heinzerling KG, Swanson A-N, Telesca D, Furst BA, Shoptaw SJ. Cigarette smoking as a target for potentiating outcomes for methamphetamine abuse treatment. Drug Alcohol Rev 2013;32:96-99] [ABSTRACT FROM AUTHOR]

Introduction and Aims. To examine the cost-effectiveness of modafinil (200 mg daily) plus counselling compared with placebo for the treatment of psychostimulant dependence. Design and Methods. Cost and outcome data were collected alongside two randomised controlled trials of modafinil 200 mg daily over 10 weeks for methamphetamine (n = 74) and cocaine dependence (n = 8), respectively. Incremental cost-effectiveness ratios representing the additional costs to achieve a given outcome were calculated for both the change in the number of stimulant-free days and quality-adjusted life years 12 weeks post-treatment. Results. The incremental cost-effectiveness ratio indicated that it would cost an additional $AUD79 to achieve an extra stimulant-free day with modafinil compared with placebo. This result was not statistically significant, but appeared to be a robust estimate after sensitivity analysis. Counselling, whether received within program or from other services, improved the cost-effectiveness of modafinil relative to placebo. Discussion and Conclusions. Strategies to improve the uptake of counselling are recommended as cost-effective.[Shearer J, Shanahan M, Darke S, Rodgers C, van Beek I, McKetin R, Mattick RP. A cost-effectiveness analysis of modafinil therapy for psychostimulant dependence. Drug Alcohol Rev 2010] [ABSTRACT FROM AUTHOR]

Aim To examine the safety and efficacy of modafinil (200 mg/day) compared to placebo in the treatment of methamphetamine dependence and to examine predictors of post-treatment outcome. Participants and design Eighty methamphetamine-dependent subjects in Sydney, Australia were allocated randomly to modafinil (200 mg/day) ( n = 38) or placebo ( n = 42) under double-blind conditions for 10 weeks with a further 12 weeks post- treatment follow-up. Measures Comprehensive drug use data (urine specimens and self-report) and other health and psychosocial data were collected weekly during treatment and research interviews at baseline, week 10 and week 22. Results Treatment retention and medication adherence were equivalent between groups. There were no differences in methamphetamine abstinence, craving or severity of dependence. Medication-compliant subjects tended to provide more methamphetamine-negative urine samples over the 10-week treatment period ( P = 0.07). Outcomes were better for methamphetamine-dependent subjects with no other substance dependence and those who accessed counselling. There were statistically significant reductions in systolic blood pressure ( P = 0.03) and weight gain ( P = 0.05) in modafinil-compliant subjects compared to placebo. There were no medication-related serious adverse events. Adverse events were generally mild and consistent with known pharmacological effects. Conclusions Modafinil demonstrated promise in reducing methamphetamine use in selected methamphetamine-dependent patients. The study findings support definitive trials of modafinil in larger multi-site trials. [ABSTRACT FROM AUTHOR]

Casein kinase 1 epsilon (CKIℇ) is a component of the DARPP-32 in second-messenger pathway. CKIℇ phosphorylates and activates DARPP-32, a key molecule in various complex signaling pathways, including dopamine and glutamine signaling, which have both been demonstrated to be main pathways in substance dependence. A recent clinical study showed that rs135745, a noncoding single nucleotide polymorphism of the 3′-untranslated region of the CSNK1E gene, was associated with the intensity of the subjective response to an oral amphetamine dose in normal volunteers. Differences in sensitivity to the drug should affect development of dependence to it. Hence, we genotyped rs135745 of the CSNK1E (MIM 600863) gene in 215 patients with methamphetamine dependence and 274 age- and gender-matched normal controls. No significant differences in genotype and allele frequencies were observed between the patients with methamphetamine dependence and controls. There was also no significant association between rs135745 and the clinical characteristics of methamphetamine dependence and co-morbid methamphetamine psychosis (e.g., age of first consumption, latency of psychosis, prognosis of psychosis after therapy, spontaneous relapse of psychotic symptoms, and poly-substance abuse status). The present findings suggest that having a genetic variant of the CSNK1E gene did not affect susceptibility to methamphetamine dependence or psychosis, at least in a Japanese population. [ABSTRACT FROM AUTHOR]

Cocaine- and amphetamine-regulated transcript (CART) was originally discovered as a peptide that increased in the rat striatum after injection of a psychostimulant drug, such as cocaine or amphetamine, and is suggested to play potential roles in drug dependence. We tested the genetic association between the CART gene and methamphetamine (METH) dependence and/or psychosis. The subjects were 203 patients with METH dependence and 239 age- and gender-matched healthy controls. Two single nucleotide polymorphisms (SNPs) of the CART gene, −156A>G and IVS1 + 224G>A, were examined . There were no significant differences in genotype and allele distributions of the polymorphisms between patients with METH dependence and/or psychosis and controls. Neither were significant differences in subgroups of clinical phenotypes, for example, age at first consumption of METH, latency to onset of psychotic symptoms after the first consumption of METH, prognosis of psychosis after therapy, complication of spontaneous relapse to a psychotic state, or multisubstance abuse status, observed. The present findings suggest that the CART gene may not play a pivotal role in the development of METH dependence and psychosis, at least in a Japanese population. [ABSTRACT FROM AUTHOR]