High-dose Buprenorphine Research Articles

Effects of two doses of buprenorphine four or six hours apart on nociceptive thresholds, pain and sedation in dogs after castration

Twenty-eight dogs were randomly allocated into two groups. They were premedicated with either 10 or 20 μg/kg buprenorphine and 0·05 mg/kg acepromazine administered intramuscularly, and then anaesthetised with intravenous thiopentone...

Dexamethasone hepatic induction in rats subsequently treated with high dose buprenorphine does not lead to respiratory depression

In humans, asphyxic deaths and severe poisonings have been attributed to high-dosage buprenorphine, a maintenance therapy for heroin addiction. However, in rats, intravenous buprenorphine at doses up to 90 mg kg(-1) was not associated with significant effects on arterial blood gases. In contrast, norbuprenorphine, the buprenorphine major cytochrome P450 (CYP) 3A-derived metabolite, is a potent respiratory depressant. Thus, our aim was to study the consequences of CYP3A induction on buprenorphine-associated effects on resting ventilation in rats. We investigated the effects on ventilation of 30 mg kg(-1) buprenorphine alone or following cytochrome P450 (CYP) 3A induction with dexamethasone, using whole body plethysmography (N=24) and arterial blood gases (N=12). Randomized animals in 4 groups received sequential intraperitoneal dosing with: (dexamethasone [days 1-3]+buprenorphine [day 4]), (dexamethasone solvent [days 1-3]+buprenorphine [day 4]), (dexamethasone [days 1-3]+buprenorphine solvent [day 4]), or (dexamethasone solvent [days 1-3]+buprenorphine solvent [day 4]). Buprenorphine alone caused a significant rapid and sustained increase in the inspiratory time (P<0.001), without significant effects on the respiratory frequency, the tidal volume, the minute volume, or arterial blood gases. In dexamethasone-pretreated rats, there was no significant alteration in the respiratory parameters, despite CYP3A induction and significant increase of the ratio of plasma norbuprenorphine-to-buprenorphine concentrations. In conclusion, dexamethasone did not modify the effects of 30 mg kg(-1) buprenorphine on rat ventilation. Our results suggest a limited role of drug-mediated CYP3A induction in the occurrence of buprenorphine-attributed respiratory depression in addicts.

Does High-Dose Buprenorphine Cause Respiratory Depression?

Buprenorphine is an opioid agonist-antagonist with a 'ceiling effect' for respiratory depression. Compared with methadone, its unique pharmacology offers practical advantages and enhanced safety when prescribed as recommended and supervised by a physician. Buprenorphine has been approved in several countries as an efficient and safe maintenance therapy for heroin addiction. Its use resulted in a salutary effect with a reduction in heroin overdose-related deaths in countries that implemented office-based buprenorphine maintenance. In France, however, where high-dose buprenorphine has been marketed since 1996, several cases of asphyxic deaths were reported among addicts treated with buprenorphine. Death resulted from buprenorphine intravenous misuse or concomitant sedative drug ingestion, such as benzodiazepines. In these situations of abuse, misuse, or in association with elevated doses of psychotropic drugs, buprenorphine may cause severe respiratory depression. Unlike other opiates, the respiratory effects from buprenorphine are not responsive to naloxone. However, the exact mechanism of buprenorphine-induced effects on ventilation is still unknown. The role of norbuprenorphine, the main N-dealkylated buprenorphine metabolite with potent respiratory depressor activity, also remains unclear. Experimental studies investigating the respiratory effects of combinations of high doses of buprenorphine and benzodiazepines suggested that this drug-drug interaction may result from a pharmacodynamic interaction. A pharmacokinetic interaction between buprenorphine and flunitrazepam is also considered. As there are many questions regarding the possible dangers of death or respiratory depression associated with buprenorphine use, we aimed to present a comprehensive critical review of the published clinical and experimental studies on buprenorphine respiratory effects.

Détournement d’usage du clonazépam (Rivotril®) : tendances récentes

Recent observations suggest the existence of clonazepam abuse. In order to determine the importance of this practice and the characteristics of these consumers, a study has been carried out, based on data from the Provence-Alpes-Côte-d'Azur and Corsica health reimbursement system. Individuals from these regions affiliated to the French health reimbursement system, who have had a prescription of clonazepam reimbursed between January 1, 2001 and February 15, 2001, have been selected. The deliveries have been monitored over a 9 month-period. 9381 subjects have been selected. A sub-group of 1.5 per cent subjects with a deviant behaviour has been identified by factorial analysis and has been compared to the sub-group without deviant behaviour. The subjects with deviant behaviour are younger and mostly male. The dosage of clonazepam is higher (10.8 mg per day versus 2.1 mg per day) with a significantly higher proportion of benzodiazepine and high-dose buprenorphine. The number of deliveries is higher (19.4 versus 5.9) as well as the number of different physicians (4.5 versus 1.5) and pharmacies (5.9 versus 1.3). This study provides some arguments in favor of the potential of abuse and dependence of clonazepam and the necessity to reinforce its monitoring. This information requires to be relayed to health professionals.

Effects of High-Dose Intravenous Buprenorphine in Experienced Opioid Abusers

Effects of High-Dose Intravenous Buprenorphine in Experienced Opioid Abusers

Buprenorphine treatment outcome in dually diagnosed heroin dependent patients: A retrospective study

The present study compared retrospectively in a clinical non-experimental setting the efficacy of buprenorphine (BUP) in different subgroups of dually diagnosed and non-dually diagnosed opioid-dependent patients: all the subjects included in the study showed severe long-lasting heroin addiction and 68.4% were affected by psychiatric comorbidity. Participants (206) (mean age 32.2 ± 8.9, 177 males–29 females) were applicants to a long-term buprenorphine treatment program (mean doses 7.9 ± 0.42 mg). Aim of the study was to evaluate dual diagnosis variables possibly influencing retention rate and abstinence from illicit drugs. The patients were divided into 5 subgroups on the basis of dual diagnosis: group 1: major depression (MD) 29.61%; group 2: generalized anxiety (GAD) (11.2%); group 3: personality disorders (PD), antisocial-borderline (21.84%); group 4: schizophrenia (SC)(6.3%); group 5: substance use disorder without overt psychiatric comorbidity (SUD) (31.1%). Group 1 patients affected by MD showed the highest retention rate at 12 months (72.1%) in comparison with the other groups of patients: group 2 GAD (39.1%), group 3 PD (17.8%), group 4 SC (7.7%) and group 5 SUD, without comorbidity (45.3%) ( p = 0.006, p < 0.001, p < 0.001, p = 0.002). Similarly, at 12 months, the patients affected by MD showed less risk of illicit opioid use (16.4%) than those affected by GAD (34.8%), PD (42.2%), SC (53.8%) and SUD without comorbidity (34.4%) ( p = 0.06, p = 0.003, p = 0.008, p = 0.017). When evaluated on the whole sample, retention rate was not influenced by dose. In contrast, the higher BUP doses were associated with less risk of illicit opioid use, than lower doses ( p < 0.001). Multivariate analysis and factor analysis showed a greater association of outcome measures (retention rate and negative urines rate) with comorbid diagnosis (depression) (respectively 0.64) than with buprenorphine doses (respectively 0.54). Our data need to be interpreted with caution because of the retrospective methodology applied to a clinical non-experimental setting. BUP seems to be more effective in opioid-dependent patients affected by depression, probably due to the kappa opioid-receptors antagonist action, counteracting dysphoria, negativism and anxiety. High doses of BUP appear to predict a better outcome, in terms of negative urines, but not in terms of retention.

Prospective multicenter observational study of 260 infants born to 259 opiate-dependent mothers on methadone or high-dose buprenophine substitution

Specialized prenatal care and substitution programs improve the perinatal prognoses of pregnant drug-abusers and their infants. Although methadone is well documented, little is known about high-dose buprenorphine (HDB). This prospective, multicenter ( n = 35) observational study included 259 women on maintenance during pregnancy: 39% on methadone and 61% on HDB. Major findings were: 46% of them received good prenatal care; 62% had peridural analgesia; 12.3% delivered prematurely (<37 weeks); mean gestational age, 38.6 weeks; mean birth weight, 2822 g. Three-quarters of the newborns developed neonatal abstinence syndrome (NAS) beginning at a mean age of 40 h, with the mean maximum Lipsitz score of 9.1 at 72 h; half of them were treated, mainly with morphine hydrochloride. No baby died. Newborns were discharged with their mothers (96%) or placed in foster care (4%). Comparing methadone with HDB, respectively, mean age at the maximum Lipsitz score was 81 h versus 66 h ( P = 0.066). The perinatal medical and social prognoses for these 259 drug addicts and their infants appeared to be improved by specialized prenatal care and was similar for methadone or BHD substitution during pregnancy.

Collaboration entre médecins et pharmaciens pour le suivi des patients sous buprénorphine haut dosage: Pratiques des médecins prescripteurs

This paper examines the collaboration between general practitioners (GPs) and pharmacists in the outpatient management of patients on high-dosage buprenorphine (HDB) treatment.A telephone survey of a sample of HDB prescribers in southeastern France questioned them about their knowledge, practices, and opinions about HDB treatment in October 2002; data from the national health insurance fund and the national statistics institute completed the study. Logistic regression was used to investigate factors associated with collaboration with pharmacists. GPs' practices were compared to assess their correlation, if any, with this collaboration.345 GPs participated in the study. Only 54% reported collaborating with dispensing pharmacists in managing patients on HDB, despite official guidelines encouraging it. Collaboration was independently related to training in addiction treatment, a favorable opinion of maintenance treatment by GPs, long experience in HDB prescription, and participation in a specialized medical network.Implementation of recommendations on physician-pharmacist collaboration requires additional training in addiction medicine for GPs and the encouragement of their participation in medical networks. On the other hand, increasing the constraints on GPs may negatively affect patients' access to care.

Buprenorphine, buprenorphine/naloxone and methadone maintenance: a cost-effectiveness analysis

The use of heroin in Australia results in disproportionate harm. Although the evidence suggests that a relatively low proportion of the population aged 14 years and over have ever used (1.4%) heroin or have used it in the past 12 months (0.2%), heroin use remains a significant cause of death, injury, illness and social harm. Research demonstrates that being in treatment leads to less heroin use, lowered mortality rates and reduced crime. Pharmacotherapy treatment in Australia involves methadone and buprenorphine. Trial data used by Doran and colleagues are used in the current analysis to extend the original analysis of methadone versus low–dose buprenorphine to include high–dose buprenorphine and the buprenorphine–naloxone combination in the maintenance of heroin dependence. Adopting a provider perspective suggests that the observed difference between the cost–effectiveness of methadone and the other treatments was not statistically significant, indicating that high–dose buprenorphine and the buprenorphine/naloxone combination can provide a viable alternative to methadone in the treatment of heroin dependence. Wider treatment choices provide greater potential to recruit a larger proportion of regular dependent users and retain them in treatment for longer. The forthcoming introduction of buprenorphine/naloxone to Australia provides an exciting opportunity to enhance the treatment of heroin dependence in this country.

Buprenorphine is protective against the depressive effects of norbuprenorphine on ventilation

High dose buprenorphine is used as substitution treatment in heroin addiction. However, deaths have been reported in addicts using buprenorphine. The role of norbuprenorphine, an N-dealkyl metabolite of buprenorphine, was hypothesized to explain these fatal cases. We determined the median intravenous lethal dose (LD(50)) of norbuprenorphine in male Sprague-Dawley rats. The effects of a single intravenous dose of 3 or 9 mg/kg norbuprenorphine alone on arterial blood gases were studied. Finally, the effect of pre- and post-administrations of buprenorphine on norbuprenorphine-induced changes on arterial blood gases were analyzed. Norbuprenorphine's LD(50) was 10 mg kg(-1). Norbuprenorphine 3 mg kg(-1) produces the rapid onset of sustained respiratory depression, as demonstrated at 20 min by a maximal significant increase in PaCO(2) (8.4+/-0.9 versus 5.7+/-0.1 kPa), decrease in arterial pH (7.25+/-0.06 versus 7.44+/-0.01), and hypoxia (8.3+/-0.6 versus 11.1+/-0.2 kPa). Buprenorphine not only protected against the effects of 3 mg kg(-1) norbuprenorphine in a dose-dependent manner but also reversed the effects when given afterward. Binding experiments suggest a role for micro- and to a lesser extent for delta-opioid receptors in buprenorphine protective effect against norbuprenorphine-induced respiratory depression. In conclusion, our data clearly show that norbuprenorphine alone causes important deleterious effects on ventilation in rats. However, buprenorphine protective effect calls into question the role for norbuprenorphine in respiratory toxicity associated with buprenorphine use.

Pain management after lumbar spinal fusion surgery using continuous subcutaneous infusion of buprenorphine

The continuous subcutaneous infusion (CSI) technique is a simple, inexpensive method for managing postoperative pain. We examined the analgesic effects of CSI of buprenorphine in patients undergoing lumbar spinal fusion surgery. The patients were randomly assigned to one of three groups for postoperative pain management: control group (n = 17), high-dose buprenorphine group (BH group, n = 17), and low-dose buprenorphine group (BL group, n = 16). Infusion solutions containing buprenorphine at concentrations of 25.0 and 16.7 microg x ml(-1) combined with droperidol at a concentration of 52.0 microg x ml(-1) were used in the BH and BL groups, respectively; and an infusion solution containing droperidol at a concentration 52.0 microg x ml(-1) was used in the control group. CSI of each solution was started at a rate of 1 ml x h(-1) and was continued for 48 h. The BH and BL groups showed significantly lower scores than the control group on the Visual Analogue Scale. There were significantly fewer administrations of flurbiprofen as a supplemental analgesic in the BL and BH groups than in the control group. The incidences of sedation and nausea were comparable in the three groups. The median number of administrations of flurbiprofen was significantly less in the BH group than in the control group on the day of the operation and on the first postoperative day, whereas the number in the BL group was less than that in the C group only on the day of the operation. CSI of buprenorphine effectively reduces pain after lumbar spinal fusion surgery without apparent side effects. This technique is simple and useful for postoperative pain management.

Buprenorphine mortality, seizures and prescription data in the UK, 1980–2002

Buprenorphine safety in overdose has been debated recently, but no mortality data related to this compound from the UK have been published. To gather together all of the buprenorphine mortality figures, a number of different sources have been checked. To inform on buprenorphine safety issues, accessible information related to its availability indicators (i.e. prescriptions; seizures) data for the 1980-2002 time frame have been sought. In the UK, during this period, buprenorphine was mentioned in 43 fatalities. Typically, victims were males in the 25-44 age group. In 12 cases (28% of total), a verdict of suicide was given. Buprenorphine was detected on its own in seven cases; more frequently, it was found together with benzodiazepines and other opiates. Large quantities of buprenorphine were prescribed both in England in 1985-1989 and in 1991-1992 in Scotland, where seizures reached their highest levels. Buprenorphine prescriptions seemed to peak again after 1999, when high dose buprenorphine formulations entered the UK market. No positive correlation was found between the number of buprenorphine deaths over the years and either buprenorphine dispensings/prescriptions or seizures. However, an increase in buprenorphine-related deaths since 1999 was identified and this may be an issue which should be carefully monitored over the next few years.

Absence de corrélation entre troubles psychiques et injection de buprénorphine haut dosage: Étude cas-témoin

In France today, the treatment of opiate and notably heroin addiction with high-dose buprenorphine (HDB) is widespread. Although this treatment has been successful to some extent, problems persist. One is that some percentage (estimated at 17-47%) of patients "misuses" their HDB, either by intravenous injection or inhalation. This misuse presents a public health problem, since injecting drug users are more frequently infected by hepatitis C, and may even jeopardize the treatment's efficacy.Our study compared a sample of 26 patients treated with sublingual HDB who reported injecting it on occasion and 27 patients under HDB who did not inject it.There was no evidence of more psychiatric disorders in the population that injected HDB than in the population that did not. Conversely, the patients injecting HDB used more illicit products, more benzodiazepines and more alcohol.Despite its efficacy, substitution treatment does not appear to provide relief for some patients. HDB injection may thus correspond to a search for a precarious balance: the disruption of the HDB kinetics induced by its injection would be aimed at enhancing the opiate effect. The consumption of other licit and illicit psychotropic agents indicates a further attempt to obtain relief from a persistent mental discomfort, over and above the substitution therapy and even its misuse. The reality of the psychological imbalance experienced with, induced by or pre-existing the heroin use requires rethinking the overall treatment. Future studies should lead to the identification of the disorders that lead these patients to seek relief in injections.

Complications infectieuses et mésusage de la buprénorphine à haut dosage

High-dose buprenorphine (HDB) treatment began in France in 1996 according to relatively unrestricted prescription rules. Continued heroin injection by patients on HDB maintenance treatment and even HDB injection remain underestimated and may lead to a variety of infectious diseases. Description of infectious complications occurring in patients receiving HDB maintenance treatment. Retrospective study of drug addicts receiving HDB maintenance treatment, injecting (or highly suspected of injecting) it, and hospitalized for infections (other than HIV or viral hepatitis) in the department of infectious and tropical diseases in Nancy University Hospital. Data collection covered 1998 through 2003. We identified 21 case reports, 9 concerning infectious endocarditis, 8 cutaneous abscesses, 2 osteoarticular infections, 1 meningitis and 1 Candida retinitis. The sex-ratio was of 1 woman for 2 men, and the patients' mean age was 29.8 years. Globally 13 patients had systemic infections. Nine patients admitted having injected HDB (and no other drugs) (including the case of Candida retinitis), while in the other 12 cases, the patients continued injecting heroin as well. The role of misused HDB was strongly suspected in those 12 infections, but was not clearly confirmed. All patients recovered from the infections. The long-term psychosocial outcome remains unknown. The cases analyzed illustrate the dual reality that HDB is often ineffective as a maintenance treatment, since some patients continue to inject heroin, and that its misuse can have infectious consequences. The results of HDB maintenance treatment substitution are mixed. The individual benefit/risk ratio must be improved. Networking is crucial, notably between physician and pharmacist, and the monitoring system must be reinforced.

Spondylodiscite à Enterobacter cloacae par mésusage intraveineux de la buprénorphine haut dosage

We report a case of Enterobacter cloacae spondylodiscitis related to risk practices in intravenous drug addicts (IVDA). The patient, a former heroin addict, was receiving long-term, high-dose buprenorphine maintenance treatment. He had been misusing the treatment, injecting it daily for several months. The clinical course included several uncommon features that are usually found in IVDA patients: subacute infection, apyrexia, and minimal inflammatory syndrome. This infection also led to the discovery of his HIV infection. Any dorsolumbar pain in IVDA patients, including those receiving regular drug maintenance treatment and especially those with HIV infection, should suggest spondylodiscitis, because of these patients' enhanced sensitivity to infection and the frequent bacteremia caused by persistent or transitory relapse involving injection (exchange of material, reuse of needles, syringes, cotton swabs, and risk of contamination through the hands or saliva).

Interaction of μ-opioid receptor agonists and antagonists with the analgesic effect of buprenorphine in mice

Buprenorphine is a potent opioid analgesic with partial agonistic properties at μ-opioid receptors. This study investigated the interaction potential with several full μ-agonists in the tail-flick test in mice. We further examined the reversibility of buprenorphine antinociception by different μ-opioid receptor antagonists. Combination of buprenorphine with morphine, oxycodone, hydromorphone and fentanyl in the analgesic dose range resulted in additive or synergistic effects. When given after the decline of the acute buprenorphine effect, both morphine and fentanyl also showed full efficacy. A moderate antagonistic effect according to the partial μ-agonistic properties of buprenorphine was only seen when high doses exceeding the therapeutic dose ranges were combined. Under these conditions antinociception of morphine was reduced to the effect of buprenorphine alone. Prophylactic administration of naloxone (10 mg/kg i.v.), naltrexone (1 mg/kg i.v.) and clocinnamox (5 mg/kg s.c.) fully and persistently blocked the antinociception of a high dose of buprenorphine. An established effect of buprenorphine was less sensitive, although repeated administration of naloxone induced complete antagonism, as did the irreversible antagonist clocinnamox under prophylactic and curative treatment conditions. Our results suggest that the antinociceptive effect of buprenorphine is mainly, if not exclusively, mediated by activation of μ-opioid receptors. They confirm clinical experience that in the analgesic dose range a switch between buprenorphine and full μ-agonists is possible without loss of analgesic efficacy and without a refractory period between the termination of buprenorphine analgesia and the onset of action of the new μ-opioid treatment. Antinociception of buprenorphine is sensitive towards μ-opioid receptor antagonists and incomplete inhibition can be improved by increasing the dose or repetitive dosing.

High-dose Buprenorphine: Perioperative Precautions and Management Strategies

Buprenorphine has been in clinical use in anaesthesia for several decades. Recently, the high-dose sublingual formulation (Subutex, Reckitt Benckiser, Slough, U.K.) has been increasingly used as maintenance therapy in opioid dependence, as an alternative to methadone and other pharmacological therapies. Buprenorphine has unique pharmacological properties making it well suited for use as a maintenance therapy in opioid dependence. However, these same properties may cause difficulty in the perioperative management of pain. Buprenorphine is a partial opioid agonist, attenuating the effects of supplemental illicit or therapeutic opioid agonists. As a result of its high receptor affinity, supplemental opioids do not readily displace buprenorphine from the opioid receptor in standard doses. High-dose buprenorphine has an extended duration of action that prolongs both of these effects. The perioperative management of patients stabilized on high-dose buprenorphine and undergoing surgery requires consideration of the likely analgesic requirements. Where possible the buprenorphine should be continued. Pain management should focus on maximizing non-opioid analgesia, local anaesthesia and non-pharmacological techniques. Where pain may not be adequately relieved by these methods, the addition of a full opioid agonist such as fentanyl or morphine at appropriate doses should be considered, accompanied by close monitoring in a high dependency unit. In situations where this regimen is unlikely to be effective, preoperative conversion to morphine or methadone may be an option. Where available, liaison with a hospital-based alcohol and drug service should always be considered.

Facteurs de risques de rupture précoce de prise en charge lors de l’induction d’un traitement substitutif par buprénorphine haut dosage: Étude chez 1085 dépendants aux opiacés

The revelation of an acceptable rate of users still treated one year after initiation of a substitution program with high-dose buprenorphine (HDB) has contributed in the validation of the interest of the molecule in this indication. However the frequency of early drop-outs (after the first consultation), when treatment is set-up, is frequently evoked, although undocumented, by general practitioners.During analysis of a survey on the follow-up of opiate addicts starting substitution therapy with HDB, we attempted to assess the frequency of early drop-outs and identify the contributing factors.Among the 1085 patients included in the study and in whom induction therapy had been prescribed, 656 were assessed after 12 months' follow-up.Age, precariousness, lack of social support and partial access to care (lack of health insurance, previous contact with the prescriber) were significantly associated with early drop-out. The consumption of psychoactive products and their administration mode, during the 30 days prior to the first consultation of those loss to follow-up, also differed from those of patients who remained within the care system.Knowledge of the factors related to frequent early drop-out during induction of HDB substitution therapy, and bearing this in mind, would permit the organisation of more attentive management and hence reduce the drop-out rate.

Opioid detoxification using high doses of buprenorphine in 24 hours: A randomized, double blind, controlled clinical trial

In recent years, interest in shortening of opioid detoxification has increased with the rising demands to find more cost-effective approaches for treatment of opioid dependence. This study was designed to evaluate the efficacy of administration of high doses of buprenorphine during 24 h in the management of acute opioid withdrawal. A total of 40 treatment-seeking opioid dependents were admitted and randomly assigned to two groups in a double blind, parallel trial. Buprenorphine was administered intramuscularly. Twenty patients received 12 mg buprenorphine in 24 h and the remaining 20 patients treated with conventional doses of buprenorphine tapered down over 5 days. Variables that were assessed included retention in treatment, rates of successful detoxification, the Subjective Opiate Withdrawal Scale (OOWS) scores, the Objective Opiate Withdrawal Scale (SOWS) scores, intensity of craving, drug side effects, and levels of hepatic enzymes (ALT and AST). There was no significant difference between the two groups on most variables. The main difference was in the time that maximal withdrawal symptoms occurred, which in the experimental protocol group appeared early while in the conventional protocol group appeared later during the detoxification period. Moreover, the experimental protocol was not only tolerated well but also accompanied with significantly less elevation in the ALT levels compared to the conventional treatment. However, patients in this group used more indomethacin and trazodone for symptom palliation. This study suggests that administration of high doses of buprenorphine in 24 h may be a reasonable approach for shortening of opioid detoxification. However, a larger study to confirm our results is warranted.

French general practitioners' prescribing high-dosage buprenorphine maintenance treatment: Is the existing training (good) enough?

In France, since 1996, any general practitioner (GP) can prescribe high-dosage buprenorphine maintenance treatment (BMT) for opioid-dependent patients. The health authorities initially provided mandatory specific training, but since 1998, such training is only delivered by specialized networks and the pharmaceutical industry. Among a random sample of GPs from southeastern France ( N=345), we found that many untrained GPs, as well as a significant minority of trained GPs, were likely to prescribe an ineffective dosage of buprenorphine or a potentially dangerous treatment (BMT+a short half-life benzodiazepine). These results highlight the necessity to edit clear guidelines, especially concerning situations of polyaddiction and psychiatric comorbidity, and to extend and improve BMT training in France with a renewed involvement of health authorities for quality control of such training. They even suggest that GPs' participation to specialized training sessions should become a mandatory prerequisite for prescribing BMT.