Nihon Arukoru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence最新文献

This study examined the efficacy of a group-based cognitive-behavioral treatment (CBT) for Japanese alcoholic outpatients. Participants (N = 169) were assigned either to a CBT-based relapse prevention group or a TAU (treatment as usual) group. The CBT group received 12-session CBT treatment with a structured treatment workbook once a week. The TAU group received usual daycare treatment including 12-step meeting, vocational training and leisure activities. Participants in the CBT group demonstrated a significantly low relapse rate at the end of treatment. Moreover, coping skills of the CBT group participants were significantly improved than those of the TAU group at the 6-month follow-up period. However, at the 6-month follow-up, the difference in relapse rates diminished. The effectiveness of CBT for alcoholics was well documented in Western countries but few studies were conducted outside of the West. The results provide support for the use of CBT for Japanese alcoholics.

Recent clinical neuroimaging studies have revealed a possible relationship between morphological brain changes and the manifestation of psychiatric disorders such as depression, schizophrenia, and alcoholism. Although its biological mechanism is still unclear, the emerging evidence suggests that the alteration of neurogenesis is the key factor for the morphological brain changes of these psychiatric disorders. In our previous work, we analyzed the mechanism of neural network disruption by ethanol using cultured cells, and found a suppressive effect of ethanol on neural stem cell (NSC) differentiation. While, we also demonstrated that antidepressants, mood stabilizers and atypical antipsychotics stimulate NSC differentiation which was inhibited by ethanol. In the present work, we have demonstrated that the usefulness of intravenous transplantation of NSCs to fetal alcohol spectrum disorder (FASD) model rat for the purpose of reconstructing the impaired neural network and investigating the possibility of regenerative therapy for patients with neurobehavioral deficits of FASD. We have shown the potential migration of transplanted NSCs into the brain by visualizing a fluorescent cell marker and radioisotope, as well as the possible recovery of behavioral abnormalities observed in FASD model rats, such as memory/cognitive function, and social interaction. We further assessed the characteristics of transplanted cells in the brain and found that the GABAergic interneurons were increased in amygdale, DG, cingulated cortex areas in the model rat. In the amygdala and cingulate Cortex of model rats, number of parvalbumin positive cells was reduced and the NSC transplantation recovered these disturbances. Moreover, in the amygdala and cingulate cortex, intravenous NSC transplantation appears to regenerate expression of post-synaptic density protein 95 (PSD95) in FASD model rats. These results indicate that intravenous NSC transplantation has the potential to become a therapeutic intervention for FASD patients.

Nicotine (NIC) regulates various cellular functions acting on the nicotinic acetylcholine receptor (nAChR). And nAChR consists of ligand-gated cation channels with pentameric structure and composed of α and β subunits. In the central nervous system, α 4 β 2 and α 7 nAChRs are the most abundantly expressed as nAChR subtypes. There are several lines of evidence indicating that systemic administration of NIC elicits the release of endogenous opioids, such as, endorphins, enkephalins and dynorphins, in the brain. NIC exerts numerous acute effects, for example, antinociceptive effects and the activating effects of the hypothalamic-pituitary-adrenal (HPA) axis. In these effects, NIC-induced antinociception, but not HPA axis activation, was inhibited by opioid receptor antagonist, naloxone (NLX), and was also suppressed in morphine tolerated mice, indicating the participation of the endogenous opioid system in NIC-induced antinociception, but not HPA axis activation. Moreover, NIC-induced antinociception was antagonized by both α 4 β 2 and α 7 nAChR antagonists, while NIC-induced HPA axis activation was antagonized by α 4 β 2 nAChR antagonist, but not by α 7 nAChR antagonist. These results suggest that the endogenous opioid system may not be located on the downstream of α 4 β 2 nAChR. On the other hand, NIC has substantial physical dependence liability. NLX elicits NIC withdrawal after repeated NIC administration evaluated by corticosterone increase as a withdrawal sign, and NLX-precipitated NIC withdrawal is inhibited by concomitant administration of other opioid receptor antagonist, naltrexone, indicating the participation of endogenous opioid system in the development of physical dependence on NIC. NLX-precipitated NIC withdrawal was also inhibited by concomitant administration of an α 7 nAChR antagonist, but not an α 4 β 2 nAChR antagonist. Taken together, these findings suggest that the endogenous opioid system may be located on the downstream of α 7 nAChR and participates in the development of physical dependence on NIC.

Objectives: Caffeine is widely available in beverages and over-the-counter products; however, in large doses, it can lead to lethal arrhythmia. This study aims to clarify the characteristics of caffeine intoxication-related deaths in Tokyo, Japan.

Subjects: Among the 4754 forensic autopsy cases between 2008 and 2013 in which a toxicological investigation was performed, cases in which the blood concentration of caffeine exceeded toxic levels (15 μg/ml) were selected (N = 22). We examined subjects' ages, medical histories, direct/underlying causes of death, and manner of death. We also assessed concurrent drug substance detection and identified the origin of the caffeine.

Results: More than 60% of the subjects were between the ages of 20 and 49 years (n = 14, 63.6%). Sixteen cases (72.7%) showed a history of psychiatric diseases such as depression and sleep disorders. The underlying cause of death for all cases except two was caffeine intoxication, and manner of death was classified as undetermined (n = 11), accidental (n = 7), suicide (n = 2), or others (n = 2). Toxicological analysis revealed the presence of ingredients common to analgesics/cold remedies in 12 cases (54.5%). The origin of the caffeine was identified in 11 cases (50.0%); the proportion of identification was significantly lower among the cases in which analgesic/cold remedy ingredients were not detected (20.0%).

Conclusions: Caffeine intoxication-related deaths mainly occurred in young and middle-aged persons with common psychiatric diseases. Psychiatrists should take note of caffeine dependence while diagnosing common psychiatric symptoms. In half of the cases, the origin of the caffeine was unidentified; nevertheless, dietary sources or over-the-counter drugs containing caffeine were suspected. As it becomes easier to obtain caffeinated products, continuous monitoring of the number of deaths from caffeine intoxication, in addition to detailed investigations of the caffeine's origin, will be necessary.

Ca2+ influx into neuron through L-type voltage-gated Ca2+ channels (VDCCs) plays an important role in psychostimulant-induced behaviroal and neuronal plasticity. On the other hand, Ca2+ release from ryanodine receptors in the endoplasmic reticulum is one mechanism altering the intracellular Ca2+ concentration. Little is known about functional relationship between psychological dependence due to drugs of abuse and L-type VDCCs or ryanodine receptors. In this paper, we review the roles and regulatory mechanisms of intracellular Ca2+ channels, especially L-type VDCCs and ryanodine receptors in brain of animals with drug dependence. Our recent study have reported that blockade of L-type VDCCs inhibits the development of rewarding effects on drugs of abuse (methamphetamine, cocaine and morphine), suggesting that up-regulation of L-type VDCCs (alpha 1C and alpha 1D subunits) occurs during the development of psychological dependence. Moreover, the critical expression of type-1 and -2 ryanodine receptors in the development of methamphetamine- and cocaine-induced rewarding effects are regulated by dopamine D1 receptors. These results suggest that changes in intracellular Ca2+ dynamics play an essential role in the development of drug dependence.

Ethanol increases brain aquaporin-4 (AQP4) expression after traumatic brain injury (TBI), leading to augment mortality and morbidity after TBI. AQP4 is regulated by sodium ion channels/transporters. Ethanol affects the ion channels/transporters. From these findings, we hypothesized that ethanol may have different effects on AQP4 expression in hypo- or hyper-sodium condition. In this study, rat primary astrocytes were incubated in iso-, hypo- or hyper-sodium MEM medium with 10% calf serum. Ethanol was added to each medium simultaneously. And to check whether hypo/hyper-sodium condition could change AQP4 expression after ethanol exposure or not, astrocytes were incubated in iso-sodium with ethanol, followed by changed to hypo/hyper-sodium with the same concentration of ethanol. Astrocyte AQP4 expression was increased in hypo-sodium exposure. Hypo-sodium with ethanol did not change AQP4 expression significantly, on the other hand, hyper-sodium with ethanol decreased AQP4 expression for short time exposure, and increased it for long time exposure. Hyper-sodium changing increased astrocyte AQP4 expression under EtOH exposure. These findings suggest that AQP4 expression is regulated by sodium ion or ion channels/transporters. And ethanol affects sodium ion channels/transporters, which is involved in AQP4 expression under ethanol.

We analyzed forensic autopsy cases to assess the relationship between alcohol consumption and external causes of death. We divided 605 autopsy cases which had been performed from 2000 to 2011 at our department into Alcohol group (n = 172, 28.4%) and Non-alcohol group (n = 433, 71.6%) according to whether alcohol could be detected in the deceased's blood. The individuals' sex and age, season when the death occurred, cause of death, type of death and circumstances of death were analyzed. Alcohol group had a significantly higher ratio of males and younger ages (both p < 0.05). There was no significant between-group difference regarding the seasons when the deaths occurred. Alcohol group had significantly greater rates of spinal injuries, abdominal injuries, traffic accidents, and accidental drowning. "Bicycling" was revealed as a related factor of the traffic accidents only in Alcohol group. In contrast, "accident on the expressway," "riding a motorcycle," and "a passenger in a vehicle" were related factors only in Non-alcohol group. We concluded that the factors of male gender and middle-to-senior age are responsible for the increased risk of external causes of death after alcohol consumption, and that alcohol consumption is one of the risk factors for accidental death. In Japan, drunk-driving-related accidents have shown a downward trend whereas bicycling-related accidents have shown an upward trend, and similar results were obtained in the present study. The low awareness of drinking-induced pitfalls may be responsible for drinking-related bicycle accidents.

Class I alcohol dehydrogenase (ADH1), a key enzyme of alcohol metabolism, contributes around 70% to the systemic alcohol metabolism and also to the acceleration of the metabolism due to chronic alcohol consumption by increasing its liver content, if the liver damage or disease is not apparent. However, the contribution of ADH1 to alcohol metabolism decreases in case of acute alcohol poisoning or chronic alcohol consumption inducing liver damage or disease. On the contrary, non-ADH pathway, which is independent of ADH1, increases the contribution to alcohol metabolism in these cases, by complementing the reduced role of ADH1. The molecular substantiality of non-ADH pathway has been still unknown in spite of the long and hot controversy between two candidates of microsomal ethanol oxidizing system (MEOS) and catalase. This research history suggests the existence of other candidates. Among ADH isozymes, Class III (ADH3) has the highest Km for ethanol and the highest resistance to pyrazole reagents of specific ADH inhibitors. This ADH3 was demonstrated to increase the contribution to alcohol metabolism in vivo dose-dependently, therefore, is a potent candidate of non-ADH pathway. Moreover, ADH3 is considered to increase the contribution to alcohol metabolism in case of alcoholic liver diseases, because the enzyme content increases in damaged tissues with increased hydrophobicity or the activity of the liver correlates with the accumulated alcohol consumptions of patients with alcoholic liver diseases. Such adaptation of ADH3 to alcohol metabolism in these pathological conditions makes patients possible to keep drinking a lot in spite of decrease of ADH1 activity and develops alcoholism seriously.

We developed the TAMA mental health and welfare center Relapse Prevention Program (TAMARPP) and evaluated the efficacy of the program. We provided the program for 59 substance abusers at Tokyo Tama Comprehensive Mental Health and Welfare Center, and conducted brief interviews and questionnaire surveys to them four times during eight months follow-up period. The main results were as follows. 1) Most of the subjects were before "hitting bottom". 2) More than half of the subjects continued participating in the program for more than 2 months and their attendance rate was fairly high. 3) Some of the subjects began joining a self-help group as N.A. and A.A. during the follow up period. 4) The mood states of the subjects were gradually improved during the period. 5) About one-third of the subjects abused substance again after two-month' program, but all of them continued to attend the program or a private counseling. Most of their families also continued having support from the center. These findings suggested it was meaningful to have such a friendly and less confrontational program as TAMARPP at our center to provide support for many substance abusers before "hitting bottom" and their families.