• Journal of Ginseng Research
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• v.47 no.4
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• pp.583-592
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• 2023

Background: Alcohol is one of the most commonly used psychoactive drugs. Due to its addictive characteristics, many people struggle with the side effects of alcohol. Korean Red Ginseng (KRG) is a traditional herbal medicine that is widely used to treat various health problems. However, the effects and mechanisms of KRG in alcohol-induced responses remain unclear. Therefore, the purpose of this study was to investigate the effects of KRG in alcohol-induced responses. Methods: We investigated two aspects: alcohol-induced addictive responses and spatial working memory impairments. To determine the effects of KRG in alcohol-induced addictive responses, we performed conditioned place preference tests and withdrawal symptom observations. To assess the effects of KRG in alcohol-induced spatial working memory impairment, Y-maze, Barnes maze, and novel object recognition tests were performed using mice after repeated alcohol and KRG exposure. To investigate the potential mechanism of KRG activity, gas chromatography-mass spectrometry and western blot analysis were performed. Results: KRG-treated mice showed dose-dependent restoration of impaired spatial working memory following repeated alcohol exposure. Furthermore, withdrawal symptoms to alcohol were reduced in mice treated with KRG and alcohol. The PKA-CREB signaling pathway was activated after alcohol administration, which was reduced by KRG. However, the levels of inflammatory cytokines were increased by alcohol and decreased by KRG. Conclusion: Taken together, KRG may alleviate alcohol-induced spatial working memory impairments and addictive responses through anti-neuroinflammatory activity rather than through the PKA-CREB signaling pathway.

• Journal of Ginseng Research
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• v.29 no.2
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• pp.86-93
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• 2005

This study was undertaken to determine the antagonism of the ginseng total saponin (GTS) on the development of nalbuphine-induced tolerance and physical dependence. GTS is blown to have antinarcotic action with a dose of 100mg/kg (i.p.) in rats. STS significantly inhibits the development of nalbuphine-induced physical dependence as well as the tolerance. The level of pCREB was elevated in the striatum by the chronic treatment with nalbuphine or GTS, how-ever, the elevation of pCREB was inhibited by the GTS co-treatment. It has been suggested that NMDA receptor and/or NO is involved in the penomena of opioid dependence and withdrawal. However, the level of nNOS and NR1 was not modulated by the treatment with nalbuphine or GTS on the cortex, hippocampus and striatum in the rat brain. These results suggest that the GTS could be used to ameliorate the nalbuphine tolerance and withdrawal symptoms.

• Journal of Hospice and Palliative Care
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• v.26 no.1
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• pp.18-21
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• 2023

The combination of oxycodone and naloxone is useful for cancer pain management. Naloxone, as a pure opioid antagonist, cannot be used simultaneously with opioids. However, owing to its low bioavailability, it can be used in an oral composite formulation. We present the case of a 55-year-old man with gastric cancer who experienced severe opioid withdrawal syndrome (OWS) triggered by oxycodone/naloxone that was successfully managed with dexmedetomidine. He had been in a stable condition on intravenous morphine to alleviate cancer pain. Intravenous morphine was switched to oral oxycodone/naloxone for discharge from the hospital. The patient suddenly developed restlessness, heartburn, and violent behavior 30 minutes after taking oxycodone/naloxone. We attempted sedation with midazolam and propofol, but paradoxical agitation and desaturation occurred. Next, we tried dexmedetomidine and the patient showed a decreased heart rate and reduced agitation. The patient was eventually stabilized by increasing the dose of dexmedetomidine. This report informs clinicians of the possibility of OWS when switching from opioids to oxycodone/naloxone, which can be overcome with the appropriate use of sedatives and dexmedetomidine depending on the patient's condition.

• Proceedings of the Korean Society for Emotion and Sensibility Conference
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• 2009.05a
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• pp.101-104
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• 2009

This study investigated compensatory mechanisms in the brain during a verbal working memory task among people with Alcohol Use Disorders (AUD). A total of 21 college male students participated in the study: eleven AUD participants and 10 normal controls. Study participants were asked to complete the Korean version of the Wechsler Adult Intelligence Scale-III (K-WAIS-III) prior to the fMRI experiment. Verbal 0-back and 2-back tasks were used to assess brain activities of the participants' verbal working memory. Brain scanning was performed on Siemens SONATA 1.5T Scanner while participants were performing the 0-back and 2-back tasks. Within the AUD group, participants with greater dependency to alcohol (based on DSM-IV criteria) in the past 1 year showed lower mean score on the 'Similarities' of the K-WAIS-III (r=-0.63, p<0.05, N=11). The more participants experienced alcohol withdrawal symptoms in the past 1 year, the lower the score they received on the K-WAIS-III 'Picture Arrangement' (r=-0.69, p<0.05, n=11). The fMRI regression results showed that individuals who present greater degree of alcohol dependency symptoms are likely to show greater brain activation in the bilateral middle frontal gyri (BA 9) during the verbal working memory task. The degree of alcohol withdrawal symptoms were associated with increased brain activation in the left superior and middle frontal gyri (BA8), left precentral gyrus (BA 6), and left inferior parietal lobule (BA 40). The study findings showed that the degree of alcohol abuse/dependence and withdrawal symptoms were associated with decreased cognitive function and increased activations in brain regions particularly important for abstract reasoning (BA 9), central executive (BA 9), or spatial storage (BA 40) during a working memory task. Therefore, these results could support previous studies suggesting that the neural system of people with ADD may adopt a brain compensatory mechanism to maintain normal level of cognitive functions.

• Korean Journal of Biological Psychiatry
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• v.13 no.3
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• pp.178-190
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• 2006

Objectives : We investigated the relationship of the alcohol withdrawal symptoms with genetic polymorphism among alcohol dependence patients. Method : The measuring instruments used in this study were the Clinical Institute Withdrawal Assessment for Alcohol(CIWA-Ar). We analyzed DRD2 TaqI A polymorphism, dopamine transporter(DAT 1) polymorphism, and catechol-O-methyltransferase(COMT) polymorphism in 108 male alcoholics and 76 healthy controls. Results : The major findings was as follows. No significant differences for genotype distribution or allele frequency were revealed comparing controls and alcoholic patients. DRD2 Taq I : The subscale score of auditory hallucination among CIWA-Ar scale in homozygote was significantly higher than in heterozygote(OR=1.34). The total score of CIWA-Ar scale in heterozygote was significantly higher than in homozygote. DAT1 : In the subject without DAT-9 gene allele, it was significantly higher of the subscale score of sweating, anxiety among CIWA-Ar scale than in the subject with DAT-9 gene allele. And The total score of CIWA-Ar scale in the subject without DAT-9 gene allele was significantly higher than in the subject with DAT-9 gene allele. COMT : The total score of CIWA-Ar scale in heterozygote was significantly higher than in homozygote. Conclusion : Our results suggest the relationship between specific genetic factors and the withdrawal symptoms of alcohol dependent patients. As the candidate gene of the severity of alcohol withdrawal syndrome, DRD2 Taq1 gene was recommended.

• Biomolecules & Therapeutics
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• v.6 no.1
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• pp.25-30
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• 1998

The roles of dopamine(DA) and N-methyl-D-aspartate(NMDA) system in the development and expression of morphine dependence were investigated by monitoring the concentrations of extracellular DA and its metabolites by in vivo microdialysis and simultaneous observation of behavioral changes in morphine dependent rats. Extracellular DA level in caudate putamen of morphine-dependent rat was decreased and the concentrations of its metabolites, dihydroxy phenylacetic acid(DOPAC) and homovanillic acid(HVA), were increased during naloxone-precipitated withdrawal. DA contents were recovered to normal levels by pretreatment of MK-801, a noncompetitive NMDA receptor antagonist, which may explain the mechanism of diminishing effect of MK-801 on withdrawal symptoms in morphine-dependent rats. MK-801(0.3 mg/tg, i.p.) induced the untoward hamful neurological signs such as ataxia and severe rotations, which may be produced by hyperactivation of dopaminergic system. These results suggest that MK-801 may inhibit the expression of mophine dependence by altering the dopamine release.

• Molecules and Cells
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• v.39 no.9
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• pp.645-653
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• 2016

Morphine is the most potent analgesic for chronic pain, but its clinical use has been limited by the opiate's innate tendency to produce tolerance, severe withdrawal symptoms and rewarding properties with a high risk of relapse. To understand the addictive properties of morphine, past studies have focused on relevant molecular and cellular changes in the brain, highlighting the functional roles of reward-related brain regions. Given the accumulated findings, a recent, emerging trend in morphine research is that of examining the dynamics of neuronal interactions in brain reward circuits under the influence of morphine action. In this review, we highlight recent findings on the roles of several reward circuits involved in morphine addiction based on pharmacological, molecular and physiological evidences.

• The Journal of Internal Korean Medicine
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• v.22 no.2
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• pp.239-243
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• 2001

Alcoholism is a chronic behavior disorder that disturbs the health, social, and economical functions by intaking alcohol repeatedly. Alcoholism includes some habituation, dependency, and addiction. It may be clinically silent or severe enough to lead to the rapid development of hepatic, renal and gastrointestinal failure. Alcoholism can also cause death. In this case, we administrated saenggangunbitang and sungjoocheonggantang to a patient suffering from alcohoism and its withdrawal symptoms. After administration of saenggangunbitang-sungjoocheonggantang medication, clinical symptoms, including liver function with diabetes mellitus and splenomegaly improved. saenggangunbitang-sungjoocheonggantang showed desirable effect on alcoholism symptoms.

• Journal of Oriental Neuropsychiatry
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• v.16 no.2
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• pp.135-148
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• 2005

Objective : The purpose of this study is to take around the oriental medical treatment about substance related disorder in china. Method : We review the studies which are published by six different journal in China since 1992 to 2002 involved in substance related disorders. Result 1. The kinds of substance which is the subject of each study. It suggest that the narcotics-withdrawal patients in china take kinds of opium many more than phillopon or barbiturate, cocain etc. especially the heroine takes the most portion in the kinds of opium. 2. The type of chinese medicine demonstration which is about the addiction and withdrawal. There are many symptoms in the each period of withdrawal, According to the each period demonstration, the herbal formula must be different. 3. The formula used in treatment and the substance which is used in common Codonopsis radix is widely used, and pinellia ternata, aractylodes japonica, citrus nobilis, vegetable worms, angelica gigas, zizyphus jujuba, panax ginseng, astragalus membranaceus etc are also used in treatment. 4. The methods of acupunture treatment Hapkok(LI-4), Naegwan(PC6), and Sanyinjiao(SP6) are the widely used acu-points. in addition to these acupoints, there are waegwan(TE5) choksamli(ST36) hanggan(LR2)etc. Conclusion : We expect that this review about substance related disorders in TCM help the clinical study of substance related disorders in Korean medicine.

• Journal of Microbiology and Biotechnology
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• v.21 no.10
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• pp.1088-1096
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• 2011

The purpose of this study was to evaluate whether wild ginseng (WG) administration could attenuate anxiety- and depression-like behaviors and expression of corticotrophin-releasing factor (CRF) and neuropeptide Y (NPY) following withdrawal from repeated morphine administration in rats. Male rats were administered daily doses of WG (50, 100, or 200 mg/kg, i.p.) for 5 days, 30 min before morphine injection (40 mg/kg, s.c). The anxiety- and depression-like behavioral responses were measured 72 h after the last morphine injection using an elevated plus maze (EPM) and forced swimming test (FST), respectively. Changes in hypothalamic CRF and NPY expressions were also examined by analyzing their immunoreactivities in the hypothalamus. Daily administration of WG significantly reduced anxiety- and depression-like behavior, and elicited the suppression of CRF expression and the stimulation of NPY expression in the hypothalamus. Our results demonstrated that WG extract might be effective at inhibiting the anxiety and depression responses due to morphine withdrawal by possibly modulating the hypothalamus CRF and NPY systems. Furthermore, these findings imply that WG extract can be used for developing new medication to cure or alleviate morphine withdrawal symptoms and to prevent relapses of morphine use.