Clinical characteristics of over‐the‐counter (OTC) drug abusers in psychiatric practice in Japan: Comparison of single and multiple OTC product abusers

Abstract Objective To examine the clinical characteristics of over‐the‐counter (OTC) drug abusers in psychiatric practice in Japan. Method We examined the attributes, ICD‐10 subcategory, and comorbid mental disorders of patients who mainly abuse OTC products and compared the clinical characteristics of single product and multiple products abusers, using the database of the “2022 Nationwide Mental Hospital Survey of Drug‐related Disorders.” Results Among the 2468 subjects included in this survey, 273 (11.1%) used OTC products as main drugs. Of these, 209 (78.3%) and 58 (21.7%) were classified into the single product group and the multiple products group, respectively. Six were excluded for unknown ingredients. By comparing these groups, we found that many of the multiple products group consisted of young women who were recently treated for drug problems. Many subjects in the group also had a short treatment period. No differences were observed between the groups regarding the ICD‐10 F1 subcategory, but many subjects in the multiple products group fulfilled the criteria of F6 “disorders of adult personality and behavior.” Conclusion OTC products are easily accessible drugs of abuse for young women in Japan. The results of this study indicate the necessity to reconsider the educational approach for preventing drug abuse, which has focused on illicit drugs. The study also indicates that some OTC products, which contain ingredients banned overseas due to their harmful effects, are still sold in Japan and that abusers for those products exist. Measures by the government are considered urgently needed

Pharmacological characterization of [125I]CHIBA-1006 binding, a new radioligand for α7 nicotinic acetylcholine receptors, to rat brain membranes

The alpha 7 nicotinic acetylcholine receptors (nAChRs) play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. However, there are currently no suitable small molecule radioligands for imaging alpha 7 nAChRs in the brain. In this study, we synthesized the novel radioligand [I-125]4-iodophenyl 1,4-diazaicyclo[3.2.2]nonane-4-carboxylate ([I-125]CHIBA-1006), a iodine-derivative of the selective alpha 7 nAChR agonist SSR180711, and studied the characterization of [I-125]CHIBA-1006 binding to rat brain membranes. The assays of [I-125]CHIBA-1006 binding to rat brain membranes were performed at 4 degrees C. The presence of a single saturable high-affinity binding component for [I-125] CHIBA-1006 in the rat brain was shown. Scatchard analysis revealed an apparent equilibrium dissociation constant (K-d) of 88.2 +/- 21.4 nM and a maximal number of binding sites (B-max) of 65.4 +/- 6.8 fmol/mg protein (mean +/- SEM, n=4). The specific binding of [I-125]CHIBA-1006 was inhibited by a number of alpha 7 nAChR-selective ligands (e.g., unlabeled CHIBA-1006, SSR180711, CHIBA-1001, MG624 and A844606), suggesting a similarity among 7 nAChR pharmacological profiles. In contrast, alpha-bungarotoxin, MLA, and nicotine showed very weak affinity for [I-125]CHIBA-1006 binding. The regional distribution of [I-125]CHIBA-1006 binding to crude membranes from dissected regions of the rat brain was different from that of [I-125] alpha-bungarotoxin binding, suggesting that [I-125]CHIBA-1006 binding sites may not be identical to [I-125]alpha-bungarotoxin binding sites in the rat brain. The present findings suggest that [I-125]CHIBA-1006 would be a useful new small molecule radioligand for alpha 7 nAChRs in the brain. (C) 2010 Elsevier B.V. All rights reserved.NeurosciencesSCI(E)2ARTICLE130-137136

)‐related disorders from fiscal year 2012 to 2014: A study in hospitals specializing in the treatment of addiction

Abstract Aims The use of new psychoactive substances (NPS) has become increasingly widespread over the last decade, in Japan and internationally. NPS are associated with a range of increasingly serious clinical, public, and social issues. Political measures to ameliorate the effects of NPS in Japan have focused on tightening regulation rather than establishing treatment methods. The current study sought to compare the neuropsychiatric symptoms of patients with NPS‐related disorders across several years. We examined patients who attended specialized hospitals for treating addiction, to elucidate the impacts of legal measures to control NPS. Methods Subjects (n = 864) were patients with NPS‐related disorders who received medical treatment at eight specialized hospitals for treating addiction in Japan between April 2012 and March 2015. Clinical information was collected retrospectively from medical records. Results Among psychiatric symptoms, the ratio of hallucinations/delusions decreased over time across 3 years of study (first year vs second year vs third year: 40.1% vs 30.9% vs 31.7%, P = 0.037). Among neurological symptoms, the ratio of coma/syncope increased over the 3‐year period (7.8% vs 11.0% vs 17.0%, P = 0.002), as did the ratio of convulsions (2.8% vs 4.3% vs 9.7%, P = 0.001). Conclusion The symptoms associated with NPS were primarily psychiatric in the first year, while the prevalence of neurological symptoms increased each year. The risk of death and the severity of symptoms were greater in the third year compared with the first year, as regulation of NPS increased

Study of effects of ifenprodil in patients with methamphetamine dependence: Protocol for an exploratory, randomized, double‐blind, placebo‐controlled trial

Abstract 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)

Risk factors for the onset of dependence and chronic psychosis due to cannabis use: Survey of patients with cannabis-related psychiatric disorders.

AIM: The objective of the current study was to identify risk factors that affect the onset of dependence and chronic psychosis due to cannabis use. METHODS: We examined clinical genetic factors, psychiatric disorders prior to cannabis use, starting age of cannabis use, duration and frequency of cannabis use, types of cannabis products used, combined use of other psychoactive substances, and the psychiatric diagnosis of 71 patients with cannabis-related psychiatric disorders who underwent treatment at nine mental health hospitals in Japan. Information was collected from cross-sectional interview surveys conducted by each patient's attending psychiatrist. RESULTS: For the diagnosis of dependence syndrome due to the use of cannabis, we found associations with the number of years of cannabis use and the use of cannabis products with a high Δ9-tetrahydrocannabinol (THC) content. However, we found no association between diagnosis of residual and late-onset psychotic disorders and clinical genetic factors, presence of preceding psychiatric disorders, duration and frequency of cannabis use, starting age of cannabis use, or combined use of other psychoactive substances; an association was found only for the absence of use of cannabis products other than dried cannabis. CONCLUSION: The onset of cannabis dependence was related to long-term cannabis use and the use of cannabis products with a high THC content. However, chronic psychosis was not associated with total THC intake or psychiatric vulnerability. Thus, unknown factors appear to be involved in the onset of chronic psychosis