Study on Therapeutic Effect of Compound Decoction of Comcide in Treating Withdrawal Reaction of Heroin Dependent Rhesuses

Objective: To observe the therapeutic effect of compound decoction of Comcide (CDC), a traditional Chinese medicine (TCM) in treating the withdrawal reaction (WR) of heroin dependent rhesuses (HDR).Methods: To study therapeutic effects of CDC and methadone in treating WR of HDR models induced by administering of heroin. Through observing, comparing and evaluating the scores of all groups gained during the first 4 days when the WR was most severe.Results: CDC and methadone had the same therapeutic effects on WR of HDR. There were significant differences between the scores of CDC and methadone, and that of natural withdrawal,P < 0. 01; while there were insignificant difference between the scores of CDC and that of methadone,P > 0.05.Conclusion: CDC had the therapeutic effect in treating WR of HDR.

THERAPEUTIC EFFECT OF ABSTINENCE CAPSULE ON WITHDRAWAL SYMPTOMS OF HEROIN ADDICTS

435 heroin addicts were treated for 10 days to evaluate the therapeutic effectiveness ofabstinence capsule on heroin withdrawal symptoms and its main adverse actions.Lofexidine was applied in a control group of 48 addicts.The single blind method and somedetermination methods used internationally were employed to evaluate the therapeuticeffectiveness and adverse actions of the drugs.The results showed that the abstinence capsulehas better therapeutic effectiveness,with less adverse actions,wider safety range,longer timeof action and less cost than lofexidine.

低频电针对海洛因心理依赖小鼠海马乙酰胆碱和多巴胺浓度的影响

目的:探讨电针淡化海洛因心理依赖小鼠成瘾记忆的中枢神经生化机制。方法:将经过CPP筛选无明显自然位置偏性的56只雌雄昆明种小鼠随机分为空白组、模型组、电针组和西药组。以海洛因剂量逐日递增原则注射并进行CPP训练制作海洛因心理依赖模型小鼠作为研究对象,电针"内关"、"三阴交"及点刺"四神聪"穴,频率2 Hz,电压2~4 V,电流1~3mA递增,刺激强度以小鼠下肢轻微抖动为度,每次10分钟,每日1次,治疗10次。运用酶联免疫法检测海马AchE浓度和DA浓度。结果:①模型组海马AchE浓度较空白组低,P<0.05;电针组海马AchE浓度较模型组明显升高,P<0.01;西药组与模型组比较,海马AchE浓度仅有升高趋势,P>0.05。②模型组海马DA浓度较空白组高,P<0.05;电针组、西药组与模型组比较,都可降低海马DA浓度,P<0.01,P<0.05。结论:电针对海洛因心理依赖小鼠具有升高海马AchE浓度和降低海马DA浓度的作用。低频电针可通过调节海洛因心理依赖小鼠成瘾记忆保持和激发的重要靶区———海马胆碱能神经系统和多巴胺系统之间的内稳态而发挥淡化成瘾记忆的作用。

Clinical Observation of Electroacupuncture in Treating Withdrawal Anxiety in Heroin-dependent Patients

Objective： To observe the effects of electroacupuncture on withdrawal anxiety in heroin-dependent patients. Methods： Sixty heroin-withdrawal subjects with negative urine morphine were digitally randomized into two groups： acupuncture group in which 30 cases were treated by electroacupuncture and control group in which 30 cases were given no treatment. The patients were assessed by Hamilton anxiety scale before treatment and one week, two weeks and three weeks after treatment. Results： After treatment, the anxiety symptoms of heroin-dependent patients were improved more significantly in the acupuncture group than in the control group （P〈0.01）. Conclusion： Electroacupuncture has good effects on anxiety symptoms and emotions of heroin-dependent patients.

Primary studies on heroin abuse and injury induced by oxidation and lipoperoxidation

Objective To further reveal serious risks of heroin abuse to human body and clarify grave injuries of oxidation, peroxidation and lipoperoxidation induced by nitric oxide and other free radicals to heroin abusers Methods Determined and compared plasma levels of nitric oxide (P NO), vitamin C (P VC), vitamin E (P VE), β carotene (P β CAR), lipoperoxides (P LPO) and erythrocyte activities of superoxide dismutase (E SOD), catalase (E CAT), glutathione peroxidase (E GSH Px) and erythrocyte level of lipoperoxides (E LPO) in 137 cases of heroin abusers (HAs) and 100 cases of healthy volunteers (HVs), used linear regression and correlation, stepwise regression and correlation to analyze correlation among heroin abusing duration (HAD), daily heroin abusing quantity (DHAQ) with above determination values in the HAs Results Compared with the above average values in the HVs group, the average values of P NO, P LPO, E LPO in the HAs group were significantly increased ( P <0 0001), the average values of P VC, P VE, P β CAR, E SOD, E CAT and E GSH Px were significantly decreased ( P <0 0001); the analysis of linear regression and correlation showed that with ascending of the HAD and DHAQ in the HAs, the values of P NO, P LPO, E LPO were gradually increased ( P <0 0001), the values of P VC, P VE, P β CAR, E SOD, E CAT, E GSH Px were gradually decreased ( P <0 0001); the analysis of stepwise regression and correlation suggested that the correlation among the HAD, DHAQ with the values of P NO, P VC, P VE was the closest Conclusion The balance between oxidation and antioxidation in the HAs was seriously destroyed, and the injuries induced by nitric oxide and other free radicals, oxidation, peroxidation and lipoperoxidation reactions to the body of HAs gravely exacerbated In the abstaining from heroin dependence, therefore, it should consider that sufficient quantum antioxidants such as VC, VE and β CAR are dosed to the HAs so as to abate the injuries to their bodies

Clinical observation of physiological and psychological reactions to electric stimulation of the amygdaloid nucleus and the nucleus accumbens in heroin addicts after detoxification

Background Stereotactic surgery has been used to treat heroin abstinence in China since 2000 by ablating the amygdaloid nucleus （AMY） and the nucleus accumbens （NAc）,which also provides opportunity to identify the relationship between these nuclei and addiction.Our study aimed to explore the physiological and psychological effects of electrically stimulating the AMY and the NAc in herein addicts after detoxification by observing changes of heart rate,arterial pressure and occurrence of euphoria similar to heroin induced euphoria.Methods A total of 70 heroin addicts after detoxification were recruited,and 61 of them were eligible to be given stereotactic surgery for heroin abstinence.The operation was carried out after determining the coordinates of all target nucleuses,and stimulation was performed at the AMY and the NAc solely or jointly.Heart rate,arterial pressure and occurrence of euphoria similar to heroin induced euphoria were recorded and analyzed.Results The average heat rate was （66±10） beats/min before electric stimulation,and significantly increased to （84±14） beats/min during stimulation,and changed to （73±12） beats/min 10 minutes after stimulation.There was a significant elevation of the average arterial pressure from 83 mmHg before stimulation to 98 mmHg during the stimulation,and it then decreased to 90 mmHg after stimulation.Forty-three of the 61 patients showed intense euphoria similar to heroin induced euphoria.The largest number （118/186） of euphoric responses occurred when the AMY and the NAc were stimulated at the same time.Odds ratio was 5.4 （95% CI： 2.4-11.9,P 〈0.0001） to quantify the association.Results from a Logistic regression model showed a positive correlation between unilateral stimulation of either the AMY or NAC and induction of euphoria （OR 〉1 ）,especially when the left AMY or left NAc was stimulated （P 〈0.05）.Conclusions Our data are consistent with existing results that the AMY and the NAc are related to addiction.Different roles in drug dependence would be suggested according to the location of the AMY and NAc.

Effect of acupuncture in intervening heroin-induced brain damage via regulating ubiquitin-proteasome pathway

Objective：To observe the effect of acupuncture in regulating ubiquitin-proteasome pathway （UPP）,and discuss the action of acupuncture in intervening heroin-induced brain damage.Methods：Thirty male Sprague-Dawley （SD） rats were divided into a control group,a model group and an acupuncture group by using the random number table.Rats in the model and acupuncture groups received intramuscular heroin injection for successive 8 d at a progressively increased dose.Afterwards,the injection was suspended for 5 d for withdrawal.The heroin relapse rat model was established by repeating the drug addiction and withdrawal process for 3 times.The control group followed the step of the model establishment,but was given intramuscular injection of normal saline at the stage of addiction and no intervention at the stage of withdrawal;the model group was given intramuscular heroin injection at a progressively increased dose at the addiction stage and no intervention at the withdrawal stage;the acupuncture group was dealt in the same way as the model group at the addiction stage,but received acupuncture at Baihui （GV 20） and Dazhui （GV 14） at the withdrawal stage,with the needles retained for 30 min each time,1 session a day,for successive 5 d.On the 39th day,brain tissues were extracted from the hippocampus and ventral tegmental area （VTA） of the three groups of rats.The apoptosis of brain nerve cells was detected by using terminal deoxynucleotidyl transferase-mediated nick and labeling （TUNEL）.The mRNA and protein expressions of ubiquitin （Ub）,ubiquitin protein ligase （E3） and 26S were examined by immunohistochemistry and quantitative real-time polymerase chain reaction （RT-qPCR）.Results：Compared with the model group,rat＇s hippocampus and VTA in the acupuncture group showed significantly fewer cells positively stained by TUNEL staining （P〈0.01）,and its mRNA and protein expressions of Ub,E3,26S were significantly lower （P〈0.01）.Conclusion：Reducing nerve cell apoptosis and regulating the mRNA and protein expressions of Ub,E3 and 26S in rat＇s hippocampus and VTA are possibly one of the action mechanisms of acupuncture in intervening heroin-induced brain damage.

Effect of Electroacupuncture on Anxiety and Craving in Heroin Addicts During Detoxification

Objective:To observe the effect of electroacupuncture at Jiaji (EX-B 2) points for anxiety and craving in heroin addicts during detoxification. Methods:A total of 60 cases were randomized into an electro-acupuncture group and a control group, 30 in each group. Cases in the electroacupuncture group were treated with electroacupuncture at Jiaji (EX-B 2) points, whereas cases in the control group were treated with Methadone and Doxepin. Then scores were graded using Zung self-rating anxiety score (SAS) and self-made visual analogue scale (VAS). The assessment was conducted once a day to record the adverse reactions. Results:After treatment, the SAS and VAS scores in the electro-acupuncture group were significantly lower than that in the control group (P<0.01). Conclusion:Electroacupuncture at Jiaji (EX-B 2) points can effectively alleviate anxiety and craving intensity in heroin addicts during detoxification.

Effect of Acupuncture on Contents of Tyrosine Hydroxylase and Glial Fibrillary Acidic Protein in Ventral Tegmental Area of Heroin Self-administrating Rats

Objective： This present study is to investigate the biochemical adaptations in the rdated brain regions of the mesolimbic dopamine system, such as the ventral tegmental area （VFA）, nucleus accumbens （NAc）, amygdale （Amy）, prefrontal cortex （PFC） , substantia nigra （SN） and caudateputamen （CPu） in response to heroin self-administration in rats and observe the effect of electroacupuncture on them. Methods. Thirty rats were trained by nose-poking response to establish stable intravenous heroin self-administration within 14 days, and then divided randomly into model group （group B） including 6 rats, withdrawal group which were withdrawn from heroin for 1 week （group C, n = 6） and for 2 weeks （group D, n= 6）, during which time they only lived in their individual home cages, and dectrtyacupuncture group which were also withdrawn from heroin for 1 week （group E, n= 6） and for 2 weeks （group F, n = 6）, during which time they were given electro-acupuncture treatment for 20 min daily and then returned to their individual home cages; in the meantime, another 6 rats were trained by nose-poking response with saline for 14 days as control （group A）; Then the leeds of tyrosine hydroxylase （TH） and glial fibrillary acidic protein （GFAP） in VFA, NAc, Amy, PFC, SN, CPu were detected with immunohistochemistry method. Results. The leeds of TH and GFAP in VFA of the heroin self administrating rats were obviously increased, and the leeds of TH and GFAP in NAc were also decreased, and these changes were not found in SN, CPu, Amy and PFC; Electro-acupuncture could promote the up regulation of TH and GFAP in VTA and down-regulation of TH and GFAP in NAc to return to the normal leeel. Conclusions： The chronic heroin self administration produced some biochemical adaptations in the related brain regions of the mesolimbic dopamine system and electroacupuncture could promote the repair of the ＂injured＂ DA neurons in VTA of heroin addicted rats and their functional recovery.

Studies on Coordinative Effect of Electroacupuncture and Methadone on Heroin Withdrawal Syndrome

Eight six heroin addicts were randomly divided into the treatment group by electroacupuncture plus Methadone and the control group by single Methadone for comparison of the therapeutic effects. Statistically there was no significant difference in the therapeutic effect （score reduction rate） between the treatment group and the control group （P〉 0.05）, In the treatment group, the dose of Methadone was half of routine dose, but the therapeutic effect was similar and side effect was less, in comparison with full dose in the control group.

Therapeutic Efficacy Observation on Acupuncture for Post-withdrawal Syndrome of Heroin Dependence

Obj ective： To observe and analyze the intervention effects of needling different points for post- withdrawal syndrome of heroin dependence, and thus provide clinical basis for screening specific points. Methods： A total of 60 males with heroin dependence were randomly allocated into 3 groups, the Neiguan （PC 6） group, the Shenmen （HT 7） group and the control group. The results were observed and evaluated before, during, and 3 weeks after treatment using the rating scale for post-withdrawal syndrome and Hamilton anxiety scale （HAMA）. Results： In regards to the control of post-withdrawal symptoms, the groups of Neiguan （PC 6） and Shenmen （HT 7） showed statistical difference when compared with the control group （P〈0.05, P〈0.01）; however, there was no statistical difference between the Neiguan （PC 6） group and Shenmen （HT 7） group （P〉0.05）. Conclusion： Acupuncture can alleviate the post-withdrawal syndrome and anxiety of heroin dependence. Although both Neiguan （PC 6） and Shenmen （HT 7） have equally remarkable effects, Shenmen （HT 7） have a better tendency for marked effect for heart-mind related symptoms.

Clinical Study on Combined Acupuncture and Psychological Desensitization Therapy for Anxiety due to Heroin Addiction

Objective： To observe the clinical efficacy of combined acupuncture and psychological desensitization therapy for anxiety in those with heroin addiction. Methods： All 90 cases were randomly allocated into a treatment group （45 cases） and a control group （45 cases）. Cases in the treatment group received 30 min of combined acupuncture and psychological desensitization therapy for each treatment, twice a week and 8 weeks in total, whereas cases in the control group received no treatment. After that, the anxiety score and state were observed. In addition, the mental state prior to and after cue-elicited heroin craving was evaluated. Results： The total and standard scores of anxiety in the treatment group were significantly reduced compared to the control group （P〈0.05）, coupled with a significant reduction of heroin craving （P〈0.01）. Conclusion： Combined acupuncture and psychological desensitization can alleviate anxiety and inhibit the short-term heroin craving.

Observations on the Efficacy of Auricular-plaster Therapy plus Medicine in Treating Heroin Addiction

Objective. To investigate the curative effect of auricular plaster therapy on heroin addiction. Methods： Sixty cases of heroin addiction were treated by auricular plaster therapy in cooperation with methadone and another 60 cases with methadone as a control. The treatment lasted 10 days. Results and conclusion： The results showed that the curative effect of auricular-plaster therapy plus methadone on heroin addiction was significantly better than that of methadone in the control group（P〈 0.01）. The rate of drug relapse was also significantly lower in the former（P〈 0.01）. It is considered that auricular-plaster therapy in cooperation with methadone is now an ideal therapeutic method for drug withdrawal.

Influence of Acupuncture on Sleep Disorders and Anxiety in Patients with Heroin Dependence

Objective： To observe the influence of acupuncture on sleep disorders and anxiety in patients with heroin dependence. Methods： Sixty-two male patients with heroin dependence were divided into two groups by random number table. Thirty-five cases in the acupuncture group were treated by puncturing Baihui （GV 20）, Neiguan （PC 6）, and Shenmen （HT 7） and moxibustion at Zusanli （ST 36）. Twenty-seven cases in the control group did not receive any therapeutic measures. The therapeutic effects were summarized after observation of 8 weeks. Results： After treatment, the global scores and standard scores of anxiety declined in comparison with those before the treatment in both two groups, but there was statistical difference only in the acupuncture group （P〈0.05）. There were no statistical differences in the global score and the standard score of anxiety between the two groups, but the standard scores in the acupuncture group reached the normal level. After treatment, only the sleep latency was obviously improved in the control group （P〈0.05）. The syndromes of sleep disorder were improved noticeable in the acupuncture group （P〈0.05）, and the actual sleep time was improved better than those in the control group （P〈0.05）, and PSQI global scores decreased below the normal level. Conclusion： Acupuncture has the effects to improve sleep disorders and anxious emotion in the patients with heroin dependence.

Effect of Electro-acupuncture on Drug-seeking Behavior of the Heroin Self-administrating Rat

Objective： This present study is to establish a rat model of intravenous heroin self-administration and observe the effect of electro-acupuncture on the heroin seeking behavior of the heroin self-administrating rat. Methods： Six Male Wistar rats were surgically implanted with an intra jugular intravenous catheters under sodium pentobarbital anesthesia, following a minimum recovery of 7 days, the rats were trained by nose-poke response with one daily 4-hour session for 14 consecutive days to self administer heroin （50 μg /kg / per injection）, the session ended after 25 infusions were earned or 4 hours had passed, whichever came first, the reinforcement schedule was fixed ratio 1 （FR1） that the rat received a heroin injection for each nose poke response. And then the rats were given electro-acupuncture treatment daily 30min prior to each session and then were trained with one daily 4-h session for 7 consecutive days. Results： Stable intravenous heroin self-administration behavior of rats was established after 7-8 days＇ drug training, electro-acupuncture given to the stable heroin self-administrating rat 30 min prior to each session could reduce the drug self-administration behavior, namely the total heroin intake in each session was reduced, especially the 1^th hour heroin intake, the initiation of first nose-poke response in each session was relayed, and the haste heroin-seeking behavior also became slower. Conclusions： The above results suggested that the electro-acupuncture had better detoxification effect.