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Aim: This prospective, randomized, controlled, rater-blinded study investigated the effect of G protein-activated inwardly rectifying potassium (GIRK) channel inhibitor ifenprodil on alcohol use in patients with alcohol dependence. Methods:The participants were 68 outpatients with alcohol dependence who were assigned to an ifenprodil group (administered 60 mg ifenprodil per day for 3 months) or control group (administered 600 mg ascorbic acid and calcium pantothenate per day for 3 months). The participants completed a questionnaire that included the frequency of alcohol drinking and presence of heavy drinking before the study period (time 1) and 3 months after the start of the study period (time 2).The alcohol use score was calculated using these two items.Results: Valid data were obtained from 46 participants (25 in the ifenprodil group and 21 in the control group). The alcohol use score at time 2 in the ifenprodil group was significantly lower than that in the control group after adjusting for the score at time 1 and some covariates. The intention-to-treat analysis of multiply imputed datasets indicated similar results. Group differences in the frequency of alcohol drinking were significant in the multiply imputed datasets but not in 46 participants. The ifenprodil group had a significantly lower rate of heavy drinking at time 2 than the control group.Conclusions: This study found an inhibitory effect of ifenprodil on alcohol use in patients with alcohol dependence. The results support the hypothesis that GIRK channel inhibitors ameliorate alcohol dependence.Trial registry: This trial was registered in the UMIN clinical trial registry (UMIN000006347).alcohol dependence, alcohol use, G protein-activated inwardly rectifying potassium channel, ifenprodil, randomized controlled study Nagisa Sugaya and Yasukazu Ogai contributed equally to this study.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. The rewarding effects of addictive substances are mediated by various molecules, and much attention has been given to the effects of G protein-activated inwardly rectifying potassium (GIRK) channels. 4 GIRK channels play an important role in signaling that is influ- The opening of GIRK channels hyperpolarizes the cell membrane to modulate neuronal excitability. Ethanol has been found to directly open GIRK channels. [8][9][10] Nucleotide sequence differences in GIRK channel subunit genes have been reportedly related to alcohol dependence and other substance use disorders. Ethanol-induced antinociception is reduced in weaver mutant mice that possess an amino acid sequence mutation of the GIRK2 subunit. 5,8 Hill et al 11 reported that GIRK2 knockout mice exhibited a reduction in saccharin aversion at a nonhypnotic dose of ethanol in a conditioned taste aversion paradigm and weaker ethano...

Objective:To demonstrate the usefulness of the Addiction Severity Index Japanese Version (ASI-J) in Japanese alcohol-dependent individuals. The ASI is a frequently used clinical and research instrument that measures severities in seven functional domains in people with substance abuse disorders.Methods:A total of 370 male inpatients with a history of alcohol dependence participated in the study. Forty-nine participants were excluded in the final analysis due to lack of reliability (i.e., patient misrepresentation or inability to understand). We used the ASI-J and a series of indexes that determined patient states during and post-treatment.Results:The correlations between ASI Composite Scores (CSs), which were calculated through a weighted formula and indicated the severity of each problem area, were significant but low in eight relations and not significant in 13 relations, indicating substantial independence of the problem areas. Significant differences were found in Family/Social CSs between abstinent and relapsed alcohol-dependent individuals. The questions of undesirable attitude were significantly related to the CSs of Employment, Drug use, Family/Social, and Psychiatric sections. Significant differences were observed in patient demographics, CS, and ASI Severity Rating (SR) and interviewer’s subjective scoring between alcohol-dependent individuals and drug abusers. CSs in Japanese alcohol-dependent individuals were generally similar to corresponding CSs in individuals from other countries, with the exception of The Netherlands.Conclusions:This study demonstrated that the ASI-J is useful for understanding individual profiles of problems for each patient and planning customized treatment. The ASI-J served as a predictive tool for relapse and compliance to treatment afterward and was shown to be useful as a comparison tool in clarifying similarities and differences between substance abuser groups.

We investigated the differential influence of family dysfunction on alcohol and methamphetamine dependence in Japan using the Addiction Severity Index (ASI), a useful instrument that multilaterally measures the severity of substance dependence. The participants in this study were 321 male patients with alcohol dependence and 68 male patients with methamphetamine dependence. We conducted semi-structured interviews with each patient using the ASI, which is designed to assess problem severity in seven functional domains: Medical, Employment/Support, Alcohol use, Drug use, Legal, Family/Social relationships, and Psychiatric. In patients with alcohol dependence, bad relationships with parents, brothers and sisters, and friends in their lives were related to current severe psychiatric problems. Bad relationships with brothers and sisters and partners in their lives were related to current severe employment/support problems, and bad relationships with partners in their lives were related to current severe family/social problems. The current severity of psychiatric problems was related to the current severity of drug use and family/social problems in patients with alcohol dependence. Patients with methamphetamine dependence had difficulty developing good relationships with their father. Furthermore, the current severity of psychiatric problems was related to the current severity of medical, employment/support, and family/social problems in patients with methamphetamine dependence. The results of this study suggest that family dysfunction differentially affects alcohol and methamphetamine dependence. Additionally, family relationships may be particularly related to psychiatric problems in these patients, although the ASI was developed to independently evaluate each of seven problem areas.

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