Buprenorphine-naloxone Combination Research Articles

B-326 Home Collected Oral Fluid Specimens Are a Viable Option for Telemedicine Based Toxicology Testing

Abstract Background A standard treatment for Substance Use Disorder (SUD) is Medication Assisted Therapy (MAT) consisting of a buprenorphine-naloxone combination medication. Typically, a urine specimen is collected during the in-office visit for the patient to receive MAT. Urine drug testing (UDT) ensures compliance and adherence with the treatment protocol and is often mandated for MAT. However, access to in-office visits and the ability to provide a specimen for UDT can be problematic for individuals undergoing MAT for SUD due to factors such as limited access to reliable transportation or distance to facilities. The COVID-19 pandemic has eased restrictions around telemedicine, including for the administration of MAT. Telemedicine can be a valuable tool to provide greater access to MAT for individuals by removing transportation barriers to treatment. Gravity Diagnostics partnered with various facilities to provide a telemedicine observed oral fluid toxicology (OFT) collection process. To understand if telemedicine OFT could provide the same information as in-office collected specimens, we compared telemedicine OFT to in-office OFT specimens and for one facility telemedicine-OFT to in-office UDT. Methods Gravity Diagnostics provides OFT through LC-MS/MS quantitative testing for over 72 analytes. Using a deidentified data set from our LIS, we identified OFT specimens that were collected either in-office or through telemedicine during a 6 month period. The ability to determine the effectiveness of telemedicine OFT was measured by examining the unexpected positivity rate of 72 analytes when compared to in-office OFT. We used 2-way ANOVA to determine if the detection rate of unexpected analytes between two collection methods were significantly different. Additionally, we identified a facility that conducted in-office UDT and telemedicine OFT on the same patient population. These data were compared in a similar manner with the unexpected positivity rate for 47 analytes subjected to 2-way ANOVA. Results When the unexpected detection rates between the in-office and telemedicine OFT were compared with a 2-way ANOVA, a P-value of 0.554 was found between the collection methods. This result indicated that the detection rates of unexpected analytes between the in-office and telemedicine collections were not significantly different. Similarly, when the unexpected detection rates between the UDT and the telemedicine-OFT were compared, a P-value of 0.391 was found between the collection methods. This result indicated that the detection rates between in office UDT and telemedicine OFT were not significantly different when compared within the same patient population. Conclusion Our data showed that telemedicine-OFT are comparable to in-office OFT for the detection of unexpected positive analytes. In addition, when the same patient population was tested by either telemedicine-OFT or in-office UDT, no significant difference in detection rates of unexpected positives is observed. Therefore, we are confident that we can utilize telemedicine-OFT to provide greater access to health care for patients undergoing MAT for SUD.

BUPRENORPHINE-NALOXONE-INDUCED NONCARDIOGENIC PULMONARY EDEMA

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Buprenorphine-naloxone is used to treat chronic pain and opioid use disorder. Each medication in this combination has been associated with noncardiogenic pulmonary edema. Here we report the case of a 56-year-old woman treated for chronic pain with buprenorphine-naloxone, and a history of multiple hospitalizations for pulmonary edema. Her buprenorphine-naloxone was held on admission and her symptoms improved gradually with supportive care. CASE PRESENTATION: A 56-year-old woman with past history significant for congestive heart failure, chronic obstructive pulmonary disease, and chronic pain treated with buprenorphine-naloxone presented to the emergency department via ambulance for altered mental status and worsening dyspnea for 3 days. Upon arrival to the ED she was tachypneic with a SpO2 of 50% on room air and required non-invasive ventilation. Physical exam revealed diminished breath sounds bilaterally and no peripheral edema. Laboratory data was significant for an elevated D-dimer and BNP. Covid-19 screening was negative. Chest x-ray showed diffuse hazy opacities. CTA chest was negative for pulmonary embolism, but did show extensive parenchymal opacities and diffuse ground glass densities bilaterally. Steroids and antibiotics were initiated, and buprenorphine-naloxone was discontinued.She described several similar prior hospitalizations, but denied ever receiving a diagnosis. Echocardiogram showed a normal ejection fraction and grade II diastolic dysfunction. Infectious and vasculitis etiologies were ruled out. The patient declined bronchoscopy. Records from prior hospitalizations revealed non-diagnostic bronchoalveolar lavage and wedge biopsies. Environmental exposure was ruled out via a peer reviewed questionnaire and negative allergen testing. With no clear etiology, the patient's hypoxia improved. We propose that the patient's presentation was secondary to noncardiogenic pulmonary edema induced by buprenorphine-naloxone. DISCUSSION: Non-cardiogenic pulmonary edema is an acute process resulting in hypoxia secondary to an increase in capillary permeability. Major causes include ARDS, pulmonary embolism, TRALI, and opioid overdose, but many other etiologies have been implicated. Buprenorphine, like other opioids, is a known cause of pulmonary edema (1). Naloxone induced pulmonary edema, while rare, has also been described (2). A review of the literature was not able to find buprenorphine-naloxone combination as a cause of non-cardiogenic pulmonary edema. We believe this patient's pulmonary edema may have been secondary to this medication's opioid effects, naloxone effects, or possibly an allergic reaction. Given the wide use of this medication physicians should be made aware of this possible complication. CONCLUSIONS: Non-cardiogenic pulmonary edema is a potential complication of buprenorphine-naloxone. REFERENCE #1: Thammakumpee G, Sumpatanukule P. Noncardiogenic Pulmonary Edema Induced by Sublingual Buprenorphine. Chest. 1994;106(1):306-308. REFERENCE #2: Bansal S, Khan R, Tietjen P. Naloxone-Induced Pulmonary Edema [abstract]. Chest. 2007;132(4):692A. DISCLOSURES: No relevant relationships by Muhammad Aboudan, source=Web Response No relevant relationships by Brandon Govan, source=Web Response No relevant relationships by Abi Waqas, source=Web Response

Mc Donalds’ model of deliverance of opioid substitution treatment in COVID-19 crisis in opioid belt in rural India : A retrospective - comparative study

IntroductionCOVID-19 has been declared as a pandemic by the World Health Organization on March, 2020. Opioid substitution therapy (OST) for opioid-dependent patients is an evidence-based, effective outpatient (OPD) based treatment maintained on medications(, buprenorphine-naloxone combination). These are difficult times for patients with addictive disorders. Authors came up with an idea of implementing “walk through” out patient model inspired by “Drive through” model of Mc Donalds in which Doctor and Nurses run open space OPD near to Medical record section to reduce the waiting time of patient, quick delivery and minimize droplet exposure.ObjectivesTo study the efficacy of Mc Donald’s model of OST in OST centre in Tarn Taran, india.MethodsThis was a restrospective-comparative study. We studied records of our patients using streatment as usual from September 2019 to March 2020 and using Mc Donald’s model (From April 2020 to October, 2020) for a period of 6 months during and before lockdown.ResultsThe average number of patients attending OST clinics during Covid lockdown was 352.8. The compliance rates significantly improved (57.82%), The drop out rates were much lower (20.78%), using Mc Donald’s model than usual treatment.ConclusionsAs per our knowledge, this study is first of its kind to study the efficacy of OST drug deliverance in pre Covid and Covid times and suggest, the new findings which can be inculcated in the other OSTs.

Polysubstance Use Common in Buprenorphine Deaths

Polysubstance Use Common in Buprenorphine Deaths

Successful use of buprenorphine-naloxone medication-assisted program to treat concurrent pain and opioid addiction after cancer therapy.

Cancer pain is often treated with opioids, a therapeutic regimen that can become a challenge in patients with an opioid use disorder (OUD). While use of the buprenorphine-naloxone combination is an effective medication-assisted treatment (MAT) for OUD, its use in pain patients with OUD has been controversial due to concerns that co-administration of buprenorphine can reduce or block analge-sia and precipitate opioid withdrawal in those patients requiring full opioid agonists. Data on its use in cancer pain patients are lack-ing. In this case series, the authors explore the frequency of buprenorphine-naloxone use and its outcomes in patients in a Compre-hensive Care Center (CCC) Pain Registry. OUD was deduced from an International Classification of Diseases (ICD-10) diagnostic code for opioid-related disorders recorded in the electronic medical records. Of 2,320 chronic cancer pain patients, 125 patients had ICD-10 code for opioid-related disorders, and 43 had a diagnosis of opioid abuse of whom 11 received buprenorphine-naloxone combina-tions. Eight patients on 18 (6-24) mg per day of buprenorphine-naloxone remained in therapy for 4 (2-7) years without opioid abuse relapse. This assessment was based on clinician's notes, the Prescription Monitoring Program, random urine drug screening, and the absence of Urgent Care Center visits for opioid withdrawal or overdose. When short-term opioids were administered for acute pain, these patients were able to taper down and stop them quickly without an opioid abuse relapse. Buprenorphine-naloxone was effec-tive as the sole analgesic in selected patients. Given its success at the CCC, buprenorphine-naloxone should be made available and strongly considered as a treatment for patients suffering from OUD during and following cancer treatment and when cancer pain re-duces or resolves.

Opioid substitution therapy with buprenorphine-naloxone during COVID-19 outbreak in India: Sharing our experience and interim standard operating procedure.

Coronavirus disease 2019 (COVID-19) has been declared as a pandemic by the World Health Organization on March 11, 2020. It has affected most countries of the world, including India. Both the disease and the unavoidable national response to it have posed unique challenges to our health-care system. A particular vulnerable group of patients is those with opioid dependence maintained on opioid substitution therapy (OST). These patients are pharmacologically dependent on the OST medication (buprenorphine, buprenorphine-naloxone combination [BNX], and methadone) for their healthy functioning and recovery. COVID-19 outbreak, lock-down, and difficult access to medical care, all are likely to induce stress and withdrawal, which is a potential risk for relapse among individuals with opioid dependence, who are anyway more vulnerable due to social, housing, living, and medical conditions. In this context, it is essential to re-strategize the existing OST services to adapt to the challenging circumstances. In this communication, we share our experience and formulate interim standard operating procedures (SOPs) for running a hospital-based OST service utilizing take-home BNX. The challenges, principles to meet the challenges, and interim SOPs are shared as being currently practiced in our center. Individual institutes, agencies, hospitals, and clinics running OST service with BNX can adapt these SOPs according to their characteristics, needs, demand, and resources; so long as, the basic principles are adhered to.

High buprenorphine-related mortality is persistent in Finland

Sublingual buprenorphine is used in opioid maintenance treatment but buprenorphine is also widely abused and causes fatal poisonings. The aim of this study was to investigate buprenorphine-positive fatalities in order to gain novel information on the magnitude and nature of buprenorphine abuse.All post-mortem toxicology cases positive for urinary buprenorphine, including fatal poisonings caused by buprenorphine and fatalities in which the cause of death was unrelated to buprenorphine, in the five year period of 2010–2014 in Finland were characterized according to urine buprenorphine and naloxone concentrations (n=775). Urine concentrations were used to assess which buprenorphine preparation had been used; mono-buprenorphine or a buprenorphine-naloxone combination, and whether they had been administered parenterally.In at least 28.8% of the buprenorphine-positive cases the drug had been administered parenterally. The majority of the parenteral users (68.6%) had taken mono-buprenorphine. Fatal poisoning was significantly more common among the identified parenteral users (65.5%) than among other users of buprenorphine products (45.3%). The proportion of buprenorphine-related poisoning was similar in identified parenteral users of mono-buprenorphine (68.6%) and buprenorphine-naloxone (64.1%). In nearly all of the fatal poisoningss the deceased had used other drugs and/or alcohol along with buprenorphine (98.7%). The median age of the deceased increased significantly over the study period, from 32 to 38 years.Our results show that there is ongoing parenteral abuse of both mono-buprenorphine and buprenorphine-naloxone combination. Parenteral users of buprenorphine put themselves into a great risk of fatal poisoning or other accidental injury death which is further exacerbated by the frequent poly-drug use.

A pilot study about the feasibility and cost-effectiveness of electronic compliance monitoring in substitution treatment with buprenorphine—naloxone combination

The purpose of the study was to investigate whether or not compliance monitoring by microchip could offer a feasible method for reducing abuse and/or diversion of medication from unsupervised substitution treatment for opioid addiction. Naturalistic, 4-week pilot study in out patients. All our patients (N = 12) on buprenorphine-naloxone combination (Suboxone) received their medication for 6 days in a compliance-monitoring device (PharmaDDSi, StoraEnso), which registers date and time of tablet removal. Patients were instructed to take all tablets as one dose. Time cues were displayed and discussed with the patients during their weekly visits for supervised drug administration and counseling. Regularity of registered time cues, treatment costs in comparison with routine treatment, patients' answers from a questionnaire on acceptability, and effect on drug diversion. Six patients showed good compliance, in two patients irregularities were minor, but in two others lack of adherence to treatment instructions was detected. Patients with several comorbid psychiatric diagnoses showed on an average the longest intervals between removal of first and last tablet of the daily dose. One-fourth of the patients reported that compliance monitoring had helped to avoid diversion. Total cost savings during the 4-week period was a reduction of 39 percent, which was mainly due to fewer visits to the clinic. Compliance monitoring by PharmaDDSI with weekly feedback was well accepted and subjectively increased compliance with substitution treatment. Future studies will show whether a technical solution for compliance monitoring in real time can help to reduce drug abuse and noncompliance in substitution treatment and other opioid treatments.

Buprenorphine-based opioid substitution therapy in India: A few observations, thoughts, and opinions.

The most evidence-based treatment for opioid dependence is opioid agonist maintenance treatment also known as opioid substitution therapy (OST). However, there are some critical, yet unaddressed issues of buprenorphine-based substitution therapy, especially in the Indian context. These comprise of generalizability of the evidence for OST, especially for natural and pharmaceutical opioids and for all age groups, optimum dose and duration of OST, and mode of treatment delivery including the frequency of dispensing. Notwithstanding the use of buprenorphine-naloxone combination, abuse and diversion are serious but often underreported problems. There is an urgent need for health services research in India on OST, focusing on these aspects. Rather than directly copying from Western models, it is important to try to understand the useful and safe program and policy options likely to be applicable in the Indian setting, with our own assets as well as vulnerabilities.

Root Causes, Clinical Effects, and Outcomes of Unintentional Exposures to Buprenorphine by Young Children

To characterize the rates, root causes, and clinical effects of unintentional exposures to buprenorphine sublingual formulations among young children and to determine whether exposure characteristics differ between formulations. Unintentional exposures to buprenorphine-containing products among children 28 days to less than 6 years old were collected from the Researched Abuse, Diversion, and Addiction-Related Surveillance System Poison Center Program and Reckitt Benckiser Pharmaceuticals' pharmacovigilance system from October 2009-March 2012. After adjustment for drug availability, negative binomial regression was used to estimate average exposure rates. Root cause assessment was conducted, and an expert clinician panel adjudicated causality and severity of moderate to severe adverse events (AEs). A total of 2380 cases were reviewed, including 4 deaths. Exposures to buprenorphine-naloxone combination film were significantly less frequent than exposures to buprenorphine tablets (rate ratio 3.5 [95% CI, 2.7-4.5]) and buprenorphine-naloxone combination tablets (rate ratio 8.8 [7.2-10.6]). The most commonly identified root causes were medication stored in sight, accessed from a bag or purse, and not stored in the original packaging. Among 536 panel review cases, the most common AEs reported for all formulations were lethargy, respiratory depression, miosis, and vomiting. The highest level AE severity did not differ significantly by formulation. Unintentional exposure to buprenorphine can cause central nervous system depression, respiratory depression, and death in young children. Exposure rates to film formulations are significantly less than to tablet formulations. Package and storage deficiencies contribute to unintentional exposures in young children.

Buprenorphine-Induced Psychotic Symptoms:

Buprenorphine-Induced Psychotic Symptoms:

Time to include buprenorphine-naloxone combination in the WHO model list of essential medicines

No abstract

Budgetary impact analysis of buprenorphine-naloxone combination (Suboxone®) in Spain

BackgroundOpioid addiction is a worldwide problem. Agonist opioid treatment (AOT) is the most widespread and frequent pharmacotherapeutic approach. Methadone has been the most widely used AOT, but buprenorphine, a partial μ-opiod agonist and a κ-opiod antagonist, is fast gaining acceptance. The objective was to assess the budgetary impact in Spain of the introduction of buprenorphine-naloxone (B/N) combination.MethodsA budgetary impact model was developed to estimate healthcare costs of the addition of B/N combination to the therapeutic arsenal for treating opioid dependent patients, during a 3-year period under the National Health System perspective. Inputs for the model were obtained from the specialized scientific literature. Detailed information concerning resource consumption (drug cost, logistics, dispensing, medical, psychiatry and pharmacy supervision, counselling and laboratory test) was obtained from a local expert panel. Costs are expressed in euros (€, 2010).ResultsThe number of patients estimated to be prescribed B/N combination was 2,334; 2,993 and 3,589 in the first, second and third year respectively. Total budget is €85,766,129; €79,855,471 and €79,137,502 in the first, second and third year for the scenario without B/N combination. With B/N combination the total budget would be €86,589,210; €80,398,259 and €79,708,964 in the first, second and third year of the analyses. Incremental cost/patient comparing the addition of the B/N combination to the scenario only with methadone is €10.58; €6.98 and €7.34 in the first, second and third year respectively.ConclusionAddition of B/N combination would imply a maximum incremental yearly cost of €10.58 per patient compared to scenario only with methadone and would provide additional benefits.

Buprenorphine in combination with naloxone at a ratio of 15:1 does not enhance antinociception from buprenorphine in healthy cats

Naloxone can enhance the antinociceptive/analgesic effects of buprenorphine in humans and rats. The antinociceptive effects of a patented 15:1 buprenorphine:naloxone combination was investigated in cats using a thermal and mechanical nociceptive model. Twelve cats received buprenorphine 10 μg/kg, naloxone 0.67 μg/kg or a buprenorphine-naloxone combination intramuscularly in a randomised cross over study. Using thermal and mechanical analgesiometry validated in the cat, pre-treatment baselines were measured. Following test drug administration, thresholds were studied for the next 24h. Naloxone did not enhance the thermal antinociceptive effect of buprenorphine. The results from this study are in agreement with previously published work showing that naloxone antagonises the effects of clinically analgesic doses of buprenorphine. Mechanical nociceptive thresholds were not affected by buprenorphine.

Pattern of consecutive urinalysis results for patients on take-home buprenorphine–naloxone in India: Do patients really take it at home?

International experience suggests that buprenorphine–naloxone combination can be misused and diverted. Little is known about the non-adherence to take-home buprenorphine–nloxone in India. A retrospective pilot study of 100 consecutive urine samples of heroin-dependent patients on take-home buprenorphine–naloxone medication was carried out. Urinalysis was done by thin layer chromatography, using a modified hydrolysis method. The mean daily dose for prescribed buprenorphine was 7.93 ± 2.73 mg/day, dispensed once or twice a week. Urinalysis results revealed that 30% of samples tested negative for prescribed drug despite being on regular take-home buprenorphine–naloxone medication. Nearly half of these patients also tested positive for a non-prescribed drug. The results and trends of urinalysis results carry important clinical implications and urges for a close monitoring for non-adherence and diversion of take-home medication.

The pharmacological treatment of opioid addiction—a clinical perspective

This article reviews the main pharmacotherapies that are currently being used to treat opioid addiction. Treatments include detoxification using tapered methadone, buprenorphine, adrenergic agonists such as clonidine and lofexidine, and forms of rapid detoxification. In opioid maintenance treatment (OMT), methadone is most widely used. OMT with buprenorphine, buprenorphine-naloxone combination, or other opioid agonists is also discussed. The use of the opioid antagonists naloxone (for the treatment of intoxication and overdose) and oral and sustained-release formulations of naltrexone (for relapse prevention) is also considered. Although recent advances in the neurobiology of addictions may lead to the development of new pharmacotherapies for the treatment of addictive disorders, a major challenge lies in delivering existing treatments more effectively. Pharmacotherapy of opioid addiction alone is usually insufficient, and a complete treatment should also include effective psychosocial support or other interventions. Combining pharmacotherapies with psychosocial support strategies that are tailored to meet the patients' needs represents the best way to treat opioid addiction effectively.

Data Do Not Support Buprenorphine as a First-Line Treatment for Addiction

Back to table of contents Previous article Next article Letters to the EditorFull AccessData Do Not Support Buprenorphine as a First-Line Treatment for AddictionANDREW BYRNE M.D.,ALEX WODAK M.D.,ANDREW BYRNE M.D.Search for more papers by this author,ALEX WODAK M.D.Search for more papers by this author,Published Online:1 Nov 2007https://doi.org/10.1176/appi.ajp.2007.07071058AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To The Editor: In the May 2007 issue of the Journal , Johan Kakko, M.D., et al. reported on an excellent randomized controlled trial of “stepped” buprenorphine versus methadone therapy for heroin dependence (1) . However, nearly two-thirds (65%) of the subjects were transferred to methadone because of continuing illicit drug consumption or cravings. Therefore, this study suggests that methadone should be the drug of first choice for maintenance treatment, and buprenorphine should be reserved for patients who do not respond well to methadone. Most trials to date have reported that methadone provides superior retention (2) . Methadone is also less expensive and easier and faster to administer than buprenorphine and is accepted as a safe treatment during pregnancy. Dr. Kakko et al. reported a nonsignificant difference in their primary outcome of 6-month treatment retention, with 77% for buprenorphine and 79% for methadone. Such high retention is unusual for trials of this kind. In addition, the high buprenorphine retention may have been partly achieved by a more rapid dose escalation and a higher mean dose (29 mg/day) than usual.Before the findings of Dr. Kakko et al. are accepted, there should be confirmation of the “noninferiority” of a standardized buprenorphine regimen in a community rather than clinic setting.Methadone is more toxic than buprenorphine. This finding may not have been apparent in the study conducted by Dr. Kakko et al., since most of their patients ultimately received methadone. In some jurisdictions, buprenorphine is already the most frequently prescribed maintenance therapy for opioid addiction. It is undoubtedly an excellent second-line treatment. Another important finding in this study was the average dose of 29 mg/day, which is more than double the average in most other studies and almost the manufacturer’s maximum recommendation of 32 mg/day. Such a large dose often takes more than 15 minutes to administer. Dr. Kakko et al. speculated that the inclusion of naloxone (not naltrexone as stated in the editorial accompanying the article) in the combination product may have contributed to the need for such an unusually high dose. Other studies have reported higher doses required for the buprenorphine-naloxone combination (3) . However, we are not aware of any rigorous “equivalence” studies comparing buprenorphine with the combination product. The recommendation by Dr. Kakko et al. that buprenorphine should be considered as the first-line medication, despite 65% of patients being transferred to methadone, is difficult to accept. While industry support is often integral to the development of new intervention strategies, it has also been shown that studies funded by the pharmaceutical industry have a greater likelihood of reporting favorable conclusions (4) . Redfern, NSW, AustraliaDarlinghurst, NSW, AustraliaDr. Byrne owns and runs a private clinic that dispenses methadone, buprenorphine, and other drug treatment. Dr. Wodak is the director of a public clinic (free to patients and government funded) that dispenses both methadone and buprenorphine.This letter (doi: 10.1176/appi.ajp.2007.07071058) was accepted for publication in July 2007.

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.

Methadone-related opioid agonist pharmacotherapy for heroin addiction. History, recent molecular and neurochemical research and future in mainstream medicine.

In 1963, Professor Vincent P. Dole at the Rockefeller University formed a small team to develop a pharmacotherapy for the management of heroin addiction. They hypothesized that heroin addiction is a disease of the brain with behavioral manifestations, and not merely a personality disorder or criminal behavior and began to address the specific question of whether a long-acting opioid agonist could be used in the long-term maintenance treatment of heroin addiction. Over the next 35 years, many studies documented the safety, efficacy and effectiveness of methadone pharmacotherapy for heroin addiction, but Federal regulations and stigmatization of heroin addiction prevented implementation of treatment. Finally, in 1999, NIH published a report unequivocally supporting methadone maintenance pharmacotherapy for heroin addiction. Two other effective opioid agonist treatments have been developed: the even longer acting opioid agonist l-alpha-acetylmethadol (LAAM) has been approved for pharmacotherapy for heroin addiction, and still under study is the opioid partial agonist-antagonist buprenorphine-naloxone combination. A variety of studies, both laboratory based and clinical, have revealed the mechanisms of action of long-acting opioid agonists in treatment, including prevention of disruption of molecular, cellular and physiologic events and, in fact, allowing normalization of those functions disrupted by chronic heroin use. Recent molecular biological studies have revealed single nucleotide polymorphisms of the human mu opioid receptor gene; the mu opioid receptor is the site of action of heroin, the major opiate drug of abuse, analgesic agents such as morphine, and the major treatment agents for heroin addiction. These findings support the early hypotheses of our laboratory that addiction may be due to a combination of genetic, drug-induced and environmental (including behavioral) factors and also, that atypical stress responsivity may contribute to the acquisition and persistence of, as well as relapse to, use of addictive drugs.

The misuse of buprenorphine and a buprenorphine-naloxone combination in Wellington, New Zealand

Two surveys of 12 months duration were undertaken on opioid users presenting to the Wellington Alcohol and Drug Centre before and after the introduction of a combination buprenorphine 0.2 mg-naloxone 0.17 mg tablet (Bu-Nx), which was launched in 1991 in the hope of reducing intravenous misuse. There was considerable intravenous (i.v.) misuse of buprenorphine 0.2 mg tablets (Bu) in 1990 with self-reports of misuse in 81% of the patients over the 4 weeks prior to presentation, and 65% of the patients had buprenorphine in their urine. In the repeat survey 57% reported misuse of the Bu-Nx combination over the previous 4 weeks, and 43% had buprenorphine ± naloxone detected in their urine. There was a reduction in the street price of Bu-Nx. One-third of the patients who used Bu-Nx i.v. reported instances of withdrawal symptoms, and subjectively the drug was less attractive to misusers. The combination product may have less misuse potential than buprenorphine alone, but it remains a preparation, in the dosages employed, that is intravenously misused.