济泰片联合氯硝西泮、曲马朵治疗海洛因依赖100例疗效观察

目的·· :观察非阿片类中药济泰片为主 ,辅以氯硝西泮、曲马朵对海洛因依赖戒断症状的疗效及不良反应。方·法· :对100例符合诊断标准的海洛因依赖者 ,进行为期10d的用药与观察。结果··:100例接受上述治疗的海洛因依赖者 ,显效66例 ,占66% ;有效30例 ,占30 % ;无效4例 ,占4%。总有效率为96 % ,其尿吗啡检测在5 -7d转阴。主要不良反应有口干和视物模糊 ,共82例 ,占82% ;16例 (16 % )出现恶心、呕吐和腹泻 ;2例 (2 % )出现谵妄。结论·· :本疗法能有效缓解轻、中度海洛因依赖者的戒断症状。不良反应轻微 ,停药后自动消失。     

Acute heroin abstinence in man: I. Changes in behavior and sleep

The purpose of this study was to examine overt behavioral characteristics and sleep during acute heroin abstinence in man. Both heroin-dependent patients and drug-free control subjects were observed and monitored on a 24-hour per day basis for 5 to 7 days. Observational data were analyzed for frequency of occurrence of various behaviors including the signs and symptoms of withdrawal. Electroencephalographic (EEG) data were scored into awake and sleep stages according to standard techniques. The heroin-dependent subjects generally displayed a higher number of observations across all recording days as compared to the controls. In addition, the signs and symptoms of withdrawal for these patients peaked on day 1 or day 2 and then declined over the remaining recording days. The EEG state data showed an increase in waking and decrease in both slow wave and REM sleep during acute heroin withdrawal. Total sleep was maximally suppressed on withdrawal days 2 and 3 and was still below normal control values on withdrawal days 5–7. REM sleep was more disrupted than slow-wave sleep during withdrawal from heroin. Results of this study indicate that heroin withdrawal produces a differential action upon central nervous system structures responsible for the various states of sleep, waking and related behaviors.     

Time-dependent changes in extinction behavior and stress-induced reinstatement of drug seeking following withdrawal from heroin in rats

RATIONALE AND OBJECTIVES: Footshock stress reliably reinstates heroin seeking in rats, but the time course of the development of this effect following drug withdrawal is not known. Here we studied the effect of intermittent footshock stress on reinstatement of heroin seeking following different withdrawal periods (1-66 days). We also studied whether changes in corticotropin-releasing factor (CRF) mRNA in the central nucleus of the amygdala (CeA) and the bed nucleus of the stria terminalis (BNST) are correlated with this reinstatement after 1 day and 6 days of heroin withdrawal. METHODS: Rats were trained to self-administer heroin (9 h/day; 0.1 mg/kg per infusion) for 10 days. Tests for extinction behavior and footshock-induced reinstatement of heroin seeking were then conducted after 1, 6, 12, 25, or 66 days of heroin withdrawal. On the test day, rats were given five to ten 60-min extinction sessions until they reached the extinction criterion of less than 15 responses per 60 min on the lever previously associated with heroin. Rats were then exposed to intermittent foot-shock (0.8 mA; 10 min), and lever-pressing behavior was recorded for 120 min. RESULTS: Reinstatement of lever-pressing behavior by footshock followed an inverted U-shaped curve with maximal responding after 6 days and 12 days of heroin withdrawal. Surprisingly, foot-shock did not reinstate lever-pressing behavior on day 1 of withdrawal. Lever pressing during extinction, prior to exposure to footshock, also followed an inverted U-shaped curve, with higher responding after 6, 12, and 25 days of heroin withdrawal. Finally, compared with control groups not exposed to shock, CRF mRNA levels in response to footshock were increased in the CeA (day 1 of withdrawal) and the dorsal BNST (day 1 and day 6), but not in the ventral BNST. CONCLUSIONS: The duration of the heroin withdrawal period is an important factor in the manifestation of (1) footshock stress-induced reinstatement of heroin seeking and (2) extinction of the heroin-reinforced behavior. Finally, the time-dependent changes in footshock stress-induced reinstatement following withdrawal from heroin were not correlated with alterations in CRF mRNA in the CeA and BNST.     

海洛因依赖者脱毒治疗中产生谵妄的临床分析

目的··：探讨海洛因依赖者于脱毒治疗中生产谵妄的影响因素。方法··：总结１９９３年８月至１９９６年８月间首次入我院接受脱毒治疗的１２３例海洛因依赖者的有关资料，并对不同情况下发生谵妄进行比较。结果··：共有５６例产生谵妄，谵妄发生率为４５．５％，以注射方式滥用毒品、健康状况较差的患者谵妄发生率明显高于其他方式滥用者（Ｐ＜０．０１），而使用美沙酮替代方式脱毒较之丁丙诺啡，谵妄发生率明显低（Ｐ＜０．０１）。结论··：海洛因戒断、精神药物的使用、躯体疾患是导致谵妄产生的主要影响因素。     

Involvement of arginine vasopressin and V1b receptor in heroin withdrawal and heroin seeking precipitated by stress and by heroin.

A previous study has shown that the stress responsive neurohormone arginine vasopressin (AVP) is activated in the amygdala during early withdrawal from cocaine. The present studies were undertaken to determine whether (1) AVP mRNA levels in the amygdala or hypothalamus, as well as hypothalamic-pituitary-adrenal (HPA) activity, would be altered during chronic intermittent escalating heroin administration (10 days; 7.5-60 mg/kg/day) or during early (12 h) and late (10 days) spontaneous withdrawal; (2) foot shock stress would alter AVP mRNA levels in the amygdala or hypothalamus in rats withdrawn from heroin self-administration (7 days, 3 h/day, 0.05 mg/kg/infusion); and (3) the selective V1b receptor antagonist SSR149415 (1 and 30 mg/kg, intraperitoneal) would alter heroin seeking during tests of reinstatement induced by foot shock stress and by heroin primes (0.25 mg/kg), as well as HPA hormonal responses to foot shock. We found that AVP mRNA levels were increased during early spontaneous withdrawal in the amygdala only. This amygdalar AVP mRNA increase was no longer observed at the later stage of heroin withdrawal. Foot shock stress increased AVP mRNA levels in the amygdala of rats withdrawn from heroin self-administration, but not in heroin na?ve rats. Behaviorally, SSR149415 dose-dependently attenuated foot shock-induced reinstatement and blocked heroin-induced reinstatement. Finally, SSR149415 blunted the HPA activation by foot shock. Together, these data in rats suggest that stress responsive AVP/V1b receptor systems (including the amygdala) may be critical components of the neural circuitry underlying the aversive emotional consequences of drug withdrawal, as well as the effect of negative emotional states on drug-seeking behavior.     

益安口服液用于海洛因依赖者脱毒Ⅳ期临床评价

目的·· :评价益安口服液治疗海洛因依赖的戒断症状及稽延性戒断症状的效果及不良反应。方法··:固定疗程、固定剂量的多中心Ⅳ期临床开放实验。海洛因中度依赖者单纯使用益安口服液 ;重度依赖者 ,前3d与美沙酮联合用药。疗程为10d。稽延性戒断症状的治疗于脱毒后d10开始 ,疗程30d ;稽延性戒断症状于用药后每5d测评一次。结果··:单独使用益安口服液组 (495例 )和与美沙酮联合组 (75例 )用药后每日戒断症状总分与各自用药前比较 ,差异有显著性(P<0.01) ;稽延性戒断症状治疗组 (109例 )每次测评稽延性症状总分与用药前相比明显下降 ,差异有显著性 (P<0.01)。益安口服液的不良反应主要有口干、腹泻、食欲不振、恶心等胃肠道反应 ,一般表现较轻 ,药物减量即可缓解。结论·· :益安口服液能有效地控制海洛因依赖者的戒断症状 ;治疗稽延性戒断症状效果肯定 ;不良反应小 ,是一安全的戒毒中药制剂     

盐酸丁丙诺啡治疗海洛因依赖73例临床疗效分析

本文应用不同剂量盐酸丁丙诺啡递减疗法对海洛因依赖轻度、中度、重度患者分三组脱毒治疗，以１０ｄ为一疗程。结果表明：对轻度患者组控制症状最彻底，治疗开始３ｄ无催瘾反应产生，ＯＷＳ总分呈直线下降，全程戒断症状轻微且波动小，ＯＷＳ总分平稳下降，减药顺利，停药后症状反复小，中度患者组次之。相反，重度患者组头３ｄ戒断症状较重，停药日症状波动明显。轻度患者组脱毒成功率为９０．９１％，中度８５．００％，重度组为６７．７４％。在治疗过程中三组病例药物不良反应轻微，未见欣快及对盐酸丁丙诺啡形成依赖，提示盐酸丁丙诺啡是一种较为理想、值得进一步推广的海洛因依赖脱毒治疗药物。     

盐酸丁两诺啡治疗海洛因依赖临床疗效评价──附631例临床报告

本文以针剂盐酸丁丙诺啡（ＢＵＰ）肌肉注射８—１０ｄ递减疗法对海洛因依赖者６３１例进行戒毒治疗，戒毒成功率为８７．６４％，脱试率为１２．３６％，通过临床治疗结果，并对其临床疗效进行评价。结果表明ＢＵＰ用于海洛因依赖的戒断治疗，选择合理递减疗程控制症状彻底，减药时戒断症状轻微平稳，治疗过程无明显兴奋及欣快表现，住院过程无强烈觅药行为，停药后戒断症状反应反复较少且不良反应轻微。本组治疗结果亦表明ＢＵＰ依赖性潜力低，成瘾性小，治疗过程无ＢＵＰ新的依赖性形成。绝大多数患者在住院期间情绪稳定，无行为偏倚，渴求淡漠，有利于心瘾的消除。治疗实践说明ＢＵＰ是一种比较好的海洛因依赖治疗药物，值得进一步推广应用。     

海洛因对大鼠谷氨酸脱氢酶基因表达的影响

目的:研究海洛因对大鼠谷氨酸脱氢酶(GDH)基因表达的影响。方法:40只成年♂Wistar大鼠随机分为4组:对照组腹腔注射(ip)生理盐水9d;给药3d组ip海洛因3d;给药9d组ip海洛因9d;停药组ip海洛因9d后停药8d。采用生化自动分析系统检测血浆及组织中GDH活性,逆转录聚合酶链反应法(RT-PCR)检测组织中GDHmRNA的含量。结果:血浆中GDH活性在海洛因给药期间逐渐增高,停药8d后仍无明显降低;大脑组织GDH活性在海洛因给药3d、海洛因给药9d及停药8d后均显著低于对照组(P<0·01);肝脏GDH活性在海洛因给药过程中降低(P<0·01),停药8d后恢复到对照组水平;小肠GDH活性在海洛因给药9d后显著高于对照组(P<0·05),停药8d后小肠GDH活性继续升高并明显高于对照组(P<0·01)和海洛因给药9d组(P<0·05)。大脑、肝脏和小肠GDHmRNA含量分别与其GDH活性变化趋势一致。结论:海洛因对大鼠不同组织GDH基因表达影响不同。     

Tolerance and sensitization to chronic escalating dose heroin following extended withdrawal in Fischer rats: possible role of mu-opioid receptors

Rationale/objectives

Heroin addiction is characterized by recurrent cycles of drug use, abstinence, and relapse. It is likely that neurobiological changes during chronic heroin exposure persist across withdrawal and impact behavioral responses to re-exposure. We hypothesized that, after extended withdrawal, heroin-withdrawn rats would express behavioral tolerance and/or sensitization in response to heroin re-exposure and that these responses might be associated with altered mu-opioid receptor (MOPr) activity.

Methods

Male Fischer rats were exposed chronically to escalating doses of heroin (7.5–75 mg/kg/day), experienced acute spontaneous withdrawal and extended (10-day) abstinence, and were re-exposed chronically to heroin. Homecage behaviors and locomotor activity in response to heroin, as well as somatic withdrawal signs, were recorded. Separate groups of rats were sacrificed after extended abstinence and MOPr expression and G-protein coupling were analyzed using [³H]DAMGO and [³⁵S]GTPγS assays.

Results

The depth of behavioral stupor was lower during the initial days of heroin re-exposure compared to the initial days of the first exposure period. Behavioral responses (e.g., stereotypy) and locomotion were elevated in response to heroin re-exposure at low doses. Rats conditioned for heroin place preference during the chronic re-exposure period expressed heroin preference during acute withdrawal; this preference was stronger than rats conditioned during chronic heroin exposure that followed chronic saline and injection-free periods. Extended withdrawal was associated with increased MOPr expression in the caudate-putamen and frontal and cingulate cortices. No changes in G-protein coupling were identified.

Conclusions

Aspects of tolerance/sensitization to heroin are present even after extended abstinence and may be associated with altered MOPr density.     

丁丙诺啡舌下含片用于海洛因依赖者脱毒治疗临床评价

目的 :评价丁丙诺啡舌下含片对海洛因依赖者脱毒的效果及不良反应。方法 :采用多中心随机双盲双模拟对照试验及无对照开放试验设计。对照试验选择 2 39例中度海洛因依赖者 ,按照 1:1:2的比例随机分入丁丙诺啡10d组、丁丙诺啡 14d组和美沙酮 14d组。另外 4 9例重度海洛因依赖者使用丁丙诺啡进行 10 - 14d脱毒治疗 ,进行开放观察。结果 :丁丙诺啡舌下含片控制戒断症状总分和主要戒断症状评分与美沙酮比较差异无显著性 (P >0 .0 5 )。焦虑量表评分丁丙诺啡组与美沙酮组比较差异也无显著性 (P >0 .0 5 )。用药前 3d丁丙诺啡单次用量最大可达 6mg ,日剂量最大为 18mg。不良反应较少 ,主要为便秘。停药后无明显戒断症状。结论 :足量使用丁丙诺啡舌下含片用于海洛因依赖脱毒治疗安全有效     

Rapid heroin detoxification using a single high dose of buprenorphine

To test the effect of 32 mg of buprenorphine on the withdrawal process from heroin, 10 street-heroin using subjects were given 32 mg of sublingual buprenorphine, following heroin abstinence of 24 hours. Withdrawal symptoms were monitored during the first few hours, and followed for six days after buprenorphine administration, after which naltrexone (50 mg) was introduced to prevent future heroin use. Nine subjects completed detoxification with negligible withdrawal symptoms and a smooth transition to naltrexone. One subject was excluded from the study due to methadone ingestion prior to experiment. These results strongly suggest that painless detoxification from heroin can be obtained by a single high dose of buprenorphine.     

Acute heroin abstinence in man: II. Alterations in rapid eye movement (REM) sleep

The purpose of this study was to examine the effects of withdrawal from heroin upon rapid eye movement (REM) sleep. Subjects included both heroin-dependent patients and drug-free controls. The drug users were young males who had an average daily intake of approximately 973 mg of 92–98% pure heroin before entering the study. All electrophysiological data were obtained via a telemetry system on a 24-hour per day basis for 5 to 7 consecutive days. EEC records were scored into the standard awake and sleep states. Results showed a marked decrease in total amount of REM sleep during heroin withdrawal. This total decrease was associated with a decrease in duration of individual REM episodes and a large decrease in the number of occurrences of REM sleep. The heroin-dependent patients during withdrawal also showed a prolonged latency from sleep onset to first REM episode and a reduced number of REM shifts per 24-hour period. No significant difference in REM sleep interval was observed between the control subjects and drug users. Some of the overt behavioral characteristics associated with heroin withdrawal may be indirectly related to the concurrent loss in REM sleep as observed in this study.     

Safety and Efficacy of Flumazenil for Reversal of Iatrogenic Benzodiazepine-Associated Delirium Toxicity During Treatment of Alcohol Withdrawal,a Retrospective Review at One Center

Both alcohol withdrawal syndrome (AWS) and benzodiazepines can cause delirium. Benzodiazepine-associated delirium can complicate AWS and prolong hospitalization. Benzodiazepine delirium can be diagnosed with flumazenil, a GABA-A receptor antagonist. By reversing the effects of benzodiazepines, flumazenil is theorized to exacerbate symptoms of AWS and precludes its use. For patients being treated for alcohol withdrawal, flumazenil can diagnose and treat benzodiazepine delirium without precipitating serious or life-threatening adverse events. Hospital admission records were retrospectively reviewed for patients with the diagnosis of AWS who received both benzodiazepines and flumazenil from December 2006 to June 2012 at a university-affiliated inpatient toxicology center. The day of last alcohol consumption was estimated from available blood alcohol content or subjective history. Corresponding benzodiazepine, flumazenil, and adjunctive sedative pharmacy records were reviewed, as were demographic, clinical course, and outcome data. Eighty-five patients were identified (average age 50.3 years). Alcohol concentrations were detectable for 42 patients with average 261 mg/dL (10–530 mg/dL). Eighty patients were treated with adjunctive agents for alcohol withdrawal including antipsychotics (n = 57), opioids (n = 27), clonidine (n = 35), and phenobarbital (n = 23). Average time of flumazenil administration was 4.7 days (1–11 days) after abstinence, and average dose was 0.5 mg (0.2–1 mg). At the time of flumazenil administration, delirium was described as hypoactive (n = 21), hyperactive (n = 15), mixed (n = 41), or not specified (n = 8). Response was not documented in 11 cases. Sixty-two (72.9 %) patients had significant objective improvement after receiving flumazenil. Fifty-six patients required more than one dose (average 5.6 doses). There were no major adverse events and minor adverse effects included transiently increased anxiety in two patients: 1 patient who received 0.5 mg on abstinence day 2 and another patient who received 0.2 mg flumazenil on abstinence day 11. This is the largest series diagnosing benzodiazepine delirium after AWS in patients receiving flumazenil. During the treatment of AWS, if delirium is present on day 5, a test dose of flumazenil may be considered to establish benzodiazepine delirium. With the limited data set often accompanying patients with AWS, flumazenil diagnosed benzodiazepine delirium during the treatment of AWS and improved impairments in cognition and behavior without serious or life-threatening adverse events in our patients.     

海洛因对大鼠肾脏功能及核苷酸与氨基酸代谢相关酶活性的影响

目的研究海洛因对大鼠肾脏功能及代谢的影响。方法50只成年♀性Wistar大鼠平均分为5组,对照组腹腔注射生理盐水12d,两给药组分别腹腔注射海洛因3d和9d,两停药组腹腔注射海洛因9d后分别停药3d和9d。自动生化分析仪分析血浆尿酸(UA)、尿素氮(UN)、肌酐(CRE)及肾脏组织谷氨酸脱氢酶(GDH)含量,比色法检测肾脏组织腺苷脱氨酶(ADA)、黄嘌呤氧化酶(XOD)、谷氨酰胺合成酶(GS)及谷氨酸(Glu)含量。结果与对照组相比,两海洛因给药组血浆中CRE及UN均无明显升高,两停药组CRE升高(P<0.05),UN在停药9d后明显升高(P<0.01);两给药组大鼠血浆UA比对照组明显升高,两停药组大鼠血浆UA与对照组无差异;各实验组大鼠肾脏ADA含量均低于对照组;与对照组比,肾脏GS含量从给药3d开始升高(P<0.01),停药9d后恢复到对照组水平;肾脏GDH给药9d后明显低于对照组(P<0.01),停药9d后高于对照组(P<0.05);实验中XOD、Glu含量无变化。结论长期应用海洛因影响肾脏组织的代谢并损害肾脏功能。     

Acute heroin abstinence in man: IV. Sleep-waking state contingencies

This study investigated the effect of acute heroin withdrawal on the pattern of sleep-waking state sequences. Subjects included drug-dependent patients using pure heroin and drug-free controls. Electrophysiological data were recorded on a 24-hour per day basis for the first 5–7 days of withdrawal. EEG records were scored according to standard criteria. Marked increases in the sequential state changes occurred during withdrawal when progressing from awake-with-alpha, stage I, stage II and rapid eye movement (REM) sleep to the awake state. Heroin withdrawal also caused significant decreases in sequential state changes when proceeding from waking or light sleep states into deeper sleep states or into REM sleep. This study revealed that heroin withdrawal caused more abrupt transitions from quiet awake or sleeping conditions into the awake state and impeded progression into slow wave or REM sleep states.     

Effects of training and withdrawal periods on heroin seeking induced by conditioned cue in an animal of model of relapse

Rationale  A high incidence of relapse can be triggered by exposure to conditioned cues previously associated with heroin. Extended access to drug and withdrawal are thought to affect the motivation for drug seeking. Objectives  The present study evaluated how different periods of training to self-administer heroin and different periods of withdrawal affected drug seeking. Materials and methods  Following 1 to 14 days of heroin self-administration, rats were left in the home environment for 1 or 14 days. Subsequently, rats were evaluated for extinction of nose poke during the first hour after being returned to the training apparatus. One hour later, a conditioned stimulus was presented to initiate cue-induced reinstatement. Results  Extending the training period from 1 to 14 days caused an escalation of reinstatement of drug seeking induced by conditioned cues. Increasing the withdrawal period from 1 to 14 days produced a similar increase in reinstatement of drug seeking induced by cues. Reinstatement of drug seeking induced by cues was augmented by pretreatment with naltrexone (1, 5 mg/kg) 24 h prior to reinstatement on day 1, but not at 14 days of withdrawal from heroin self-administration. Conclusions  These experiments demonstrate that increasing the duration of either heroin self-administration or the withdrawal periods from heroin self-administration augments the reinstatement induced by cues that were associated previously with heroin reinforcement. Additionally, we provide one of the first demonstrations that opiate withdrawal induces heroin seeking, as assessed in the reinstatement model.     

Metabolomic profiling of brain tissues of mice chronically exposed to heroin

The chronic neurotoxicity of heroin on the nervous system is poorly understood. To address this issue, we comprehensively assessed the alteration of brain metabolomics caused by chronic heroin exposure and the withdrawal of heroin. Male C57BL/6J mice (n = 10) were given heroin (15 μmol/kg, i.p., twice a day) for 12 days while the withdrawal group received saline-treatment instead of heroin for the last two days. The control group received saline. We developed an UPLC-TOF/MS-based metabolomic approach to analyze the metabolites and carry out a metabolic pathway analysis in the brain. The major metabolites contributing to the discrimination were identified as amino acids, tricarboxylic-acid cycle intermediates, neurotransmitters, nucleotides and other compounds. A marked reduction in histidine and a slight but significant increase in phenylalanine and tryptophan were observed after heroin was withdrawn while the increased level of catecholamines was restored to baseline. Interestingly, N-acetylserotonin - a precursor of melatonin - was increased with the withdrawal of heroin while melatonin was markedly reduced along with the sub-chronic exposure to heroin. This shows that heroin disrupts not only the energy metabolism but also the biosynthesis of both catecholamines and melatonin in the mouse brain. Therefore, these substances are candidate biomarkers for chronic heroin-abuse.     

Antagonist-precipitated heroin withdrawal under anaesthetic prior to maintenance naltrexone treatment: determinants of withdrawal severity

This study sought to characterize antagonist-precipitated heroin withdrawal during and immediately following anaesthesia and to identify the determinants of withdrawal severity and duration in 48 dependent heroin users. Objective withdrawal signs decreased significantly with each naloxone bolus administered under anaesthetic. The cost (amount) of the final heroin administration and the number of hours between last heroin use and commencement of anaesthesia were significant, independent predictors of the severity of withdrawal symptomatology. While 83% (40/48) of participants completed withdrawal according to objective criteria and commenced maintenance naltrexone treatment, almost half (22/48) were unable to commence naltrexone on the day of the procedure due to residual withdrawal signs. Fourteen of these 22 participants subsequently commenced naltrexone (median number of days between admission and commencement of naltrexone was 2, range 1 - 6) while eight left treatment prior to initiation of naltrexone. Significantly fewer of those with more severe withdrawal signs during anaesthesia commenced naltrexone (40% vs. 60%). While the severity and duration of withdrawal symptomatology may be moderated by encouraging participants to reduce (or cease) heroin use close to the time of withdrawal, for a substantial proportion of participants in this study, heroin withdrawal by this antagonist-precipitated procedure was neither rapid nor painless. [Ali R, Thomas P, White J, McGregor C, Danz,C, Gowing L, Stegink A, Athanasos P. Antagonist-precipitated heroin withdrawal under anaesthetic prior to maintenance naltrexone treatment: determinants of withdrawal severity. Drug Alcohol Rev 2003;22:425 - 431]     

Effects of a high-dose fast tapering buprenorphine detoxification program on symptom relief and treatment retention

A large number of patients with heroin dependency fail to enter a treatment program because of dropping out during or immediately after detoxification. This article presents an open study of symptom relief of 10 patients withdrawing from heroin with a high-dose rapid tapering buprenorphine detoxification protocol. It also presents a pseudo-experimental comparison between 208 patients treated with a clonidine/dextropropoxiphene detoxification protocol and 246 patients treated with the high-dose rapid tapering buprenorphine detoxification protocol to evaluate differences in patients' ability to continue in treatment of addiction immediately after detoxification. The results indicate that 24 mg of sublingually administered buprenorphine beginning when the patient judges himself to be in a withdrawal state followed by another three days of daily administered and rapidly decreased doses resulted in a significant reduction of withdrawal symptoms. Also, when the clonidine/dextropropoxiphene protocol was replaced with this buprenorphine protocol the number of patients continuing in treatment immediately after discharge from the detoxification ward increased from 41.3% to 58.1%. Buprenorphine given in high doses with rapid tapering when withdrawal symptoms occur seems to offer an effective symptom-alleviating treatment, probably also decreasing the number of drop-outs after detoxification.