buprenorphine and Morphine-Dependence

Abuse of prescription opioid medications has increased dramatically in the United States during the past decade, as indicated by a variety of epidemiological sources. However, few studies have systematically examined the relative reinforcing effects of commonly abused opioid medications. The current double-blind, placebo-controlled in-patient study was designed to compare the effects of intravenously delivered fentanyl (0, 0.0625, 0.125, 0.187, and 0.250 mg/70 kg), oxycodone (0, 6.25, 12.5, 25, and 50 mg/70 kg), morphine (0, 6.25, 12.5, 25, and 50 mg/70 kg), buprenorphine (0, 0.125, 0.5, 2, and 8 mg/70 kg), and heroin (0, 3.125, 6.25, 12.5, and 25 mg/70 kg) in morphine-maintained heroin abusers (N=8 completers maintained on 120 mg per day oral morphine in divided doses (30 mg q.i.d.)). All of the participants received all of the drugs tested; drugs and doses were administered in non-systematic order. All of the drugs produced statistically significant, dose-related increases in positive subjective ratings, such as 'I feel a good drug effect' and 'I like the drug.' In general, the order of potency in producing these effects, from most to least potent, was fentanyl>buprenorphine>or=heroin >morphine=oxycodone. In contrast, buprenorphine was the only drug that produced statistically significant increases in ratings of 'I feel a bad drug effect' and it was the only drug that was not self-administered above placebo levels at any dose tested. These data suggest that the abuse liability of buprenorphine in heroin-dependent individuals may be low, despite the fact that it produces increases in positive subjective ratings. The abuse liabilities of fentanyl, morphine, oxycodone, and heroin, however, appear to be similar under these experimental conditions.

Topics: Adult; Analysis of Variance; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Prescriptions; Female; Heroin Dependence; Humans; Male; Morphine Dependence; Narcotic Antagonists; Narcotics; Pain Measurement; Pupil; Reinforcement, Psychology; Respiration

The effects of daily buprenorphine treatment (4 or 8 mg/day, sublingual) on reports of subjective effects after single intravenous doses of morphine (10 mg), cocaine (30 mg), and saline placebo were studied on an inpatient clinical research ward in 26 men concurrently dependent on opioids and cocaine (DSM-III-R). Latency to detection and certainty of a drug effect, as well as drug quality (intensity, euphoria, and dysphoria), were studied before and after 10 to 12 days of buprenorphine maintenance. Saline was accurately identified by all 26 patients during the drugfree baseline and by 25 patients during buprenorphine maintenance conditions. All patients accurately identified morphine during the drugfree period before treatment with buprenorphine, but 18 (69%) of 26 patients were unable to detect morphine during buprenorphine maintenance and 2 misidentified morphine as cocaine. Six men (23%) accurately identified morphine and reported that the intensity and quality of morphine's effects were equivalent to drugfree conditions. Cocaine levels in plasma 5 minutes after intravenous cocaine injection were equivalent before and during buprenorphine treatment and averaged 282.8 +/- 43.6 and 295.2 +/- 28.8 ng/ml during 4 and 8 mg/day of buprenorphine maintenance, respectively. All patients accurately identified cocaine before and during buprenorphine maintenance, and there were no significant changes in latency to detection and certainty of a drug effect or reports of cocaine-induced intensity or euphoria during buprenorphine treatment. The concordance between responses to morphine and cocaine during inpatient buprenorphine maintenance and drug use during the first 4 weeks of outpatient buprenorphine treatment was also examined in 16 men. The effects of buprenorphine on individual responses to an acute intravenous dose of morphine or cocaine during the inpatient study did not reliably predict the frequency of heroin or cocaine self-administration during the first 4 weeks of daily outpatient buprenorphine maintenance.

Topics: Administration, Sublingual; Adult; Ambulatory Care; Arousal; Buprenorphine; Cocaine; Dose-Response Relationship, Drug; Heroin Dependence; Humans; Male; Morphine; Morphine Dependence; Prognosis; Substance Abuse, Intravenous; Substance-Related Disorders; Treatment Outcome

Opioid use disorders are commonly treated by long-acting agonist opioids including methadone and buprenorphine which could affect various aspects of male reproduction especially spermatogenesis.. We aimed to determine whether detoxification with methadone or buprenorphine was associated with reproductive disorders in male mice.. We orally induced morphine dependence in NMRI male mice, and then performed detoxification programs using either methadone or buprenorphine. Testis architecture and sperm parameters including sperm nuclear DNA integrity, mitochondrial activity, oxidative stress in seminal plasma, and routine sperm parameters were assessed to find the involved mechanisms.. The number of Leydig cells and the thickness of germinal epithelium reduced following morphine use and increased differently after detoxification with methadone or buprenorphine. Morphine dependence and detoxification with methadone and buprenorphine had different effects on sperm parameters. Morphine altered chromatin integrity, mitochondrial activity, and oxidative stress in sperm. Detoxification with methadone improved mitochondrial activity but worsened chromatin integrity, whereas detoxification with buprenorphine improved neither chromatin integrity nor mitochondrial activity. Seminal plasma oxidative stress was higher in the treated groups compared to control groups but was comparable among treatment groups. Our study revealed that long-term morphine use followed by detoxification with methadone or buprenorphine impairs testis structure and sperm parameters. Detoxification from morphine use with methadone and buprenorphine led to different preclinical outcomes in semen quality parameters, including chromatin integrity. Therefore, clinical detoxification protocols should be performed more cautiously, considering the desire of the individuals to reproduce.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Chromatin; Male; Methadone; Mice; Morphine; Morphine Dependence; Opiate Substitution Treatment; Opioid-Related Disorders; Reproduction; Semen; Semen Analysis

Opioid dependence is a major public health issue without optimal therapeutics. This study investigates the potential therapeutic effect of dezocine, a nonaddictive opioid, in opioid dependence in rat models.. Dezocine was administered intraperitoneally to a morphine-dependent rat model to investigate its effect on withdrawal and conditioned place preference (CPP). Effect of dezocine on morphine withdrawal syndrome and CPP was analyzed using 2-way analysis of variance (ANOVA) followed by Tukey's post hoc test. Buprenorphine and vehicle solution containing 20% (v/v) dimethyl sulfoxide were used for positive and negative control, respectively. The astrocytes activation in nucleus accumbens was assessed by immunofluorescence assay of glial fibrillary acidic protein. Effect of dezocine and buprenorphine on the internalization of κ opioid receptor (KOR) was investigated using Neuro2A expressing KOR fused to red fluorescent protein tdTomato (KOR-tdT). Buprenorphine and dezocine were screened against 44 G-protein-coupled receptors, ion channels, and transporter proteins using radioligand-binding assay to compare the molecular targets.. The mean withdrawal score was reduced in rats treated with 1.25 mg·kg dezocine compared to vehicle-treated control animals starting from the day 1 (mean difference: 7.8; 95% confidence interval [CI], 6.35-9.25; P < .0001 by 2-way ANOVA). Significance was observed at all treatment days, including day 7 (mean difference: 2.13; 95% CI, 0.68-3.58; P < .001 by 2-way ANOVA). Furthermore, dezocine inhibited the reinstatement of morphine-induced CPP (mean difference: 314; 95% CI, 197.9-430.1; P < .0001 by 2-way ANOVA) compared to the control group. Chronic morphine administration induced astrocytes activation in nucleus accumbens, which was attenuated by dezocine. Dezocine blocked the agonist-induced KOR internalization in vitro, 1 of the mechanisms involved in the downstream signaling and development of opioid dependence. Dezocine had affinity to norepinephrine and serotonin transporters and sigma-1 receptor, whereas buprenorphine showed no activity against these targets.. Dezocine could potentially be used to alleviate opioid dependence. Due to the unique molecular target profile different from buprenorphine, it might have important value in studying the mechanisms of morphine dependence and developing novel therapeutic approaches.

Topics: Analgesics, Opioid; Analysis of Variance; Animals; Astrocytes; Bridged Bicyclo Compounds, Heterocyclic; Buprenorphine; Cell Line; Dose-Response Relationship, Drug; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; Male; Morphine; Morphine Dependence; Narcotic Antagonists; Nucleus Accumbens; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa; Tetrahydronaphthalenes

Topics: Analgesics, Opioid; Animals; Brain; Brain Mapping; Buprenorphine; Cross-Sectional Studies; Disease Models, Animal; Female; Fluorodeoxyglucose F18; Glucose; Longitudinal Studies; Male; Methadone; Morphine; Morphine Dependence; Positron-Emission Tomography; Radiopharmaceuticals; Rats, Sprague-Dawley; Sex Characteristics; Treatment Outcome

Use of opioid agonist treatments for prescription opioid (PO) dependence is rapidly increasing. Current guidelines are based on research with heroin users. This study aimed to examine methadone and buprenorphine dose requirements for PO-dependent people.. A retrospective case series of PO-dependent patients entering methadone and buprenorphine treatment. Daily oral morphine equivalent (OME) doses at baseline were calculated using standard dose conversion calculations. Dose conversion tables were used to estimate opioid agonist doses, based on starting dose of PO. Baseline methadone and buprenorphine dose at days 7 and 28 were examined. Linear models were fit to the data.. Participants (n = 44) were 67% male, mean age 41 years (SD 10 years); 69% reported a pain condition. The methadone group (n = 21) had a mean PO dose of 704.5 mg OME (SD 783.5 mg) prior to treatment, and mean methadone dose of 45.3 mg (SD 13.1 mg) at day 7 and 61.6 mg (SD 20.8 mg) at day 28. The buprenorphine group (n = 23) had a mean PO dose of 771.7 mg OME (SD 867.7 mg) prior to treatment, with a mean dose of 14.6 mg (SD 8.3 mg) at day 7 and 18.1 (SD 8.9 mg) at day 28. Linear relationships were not found between OME and opioid agonist dose.. Opioid agonist dosages varied substantially between individuals, and from predicted dosages based on dose conversion tables. Use of conversion tables to guide selection of opioid agonist dosage may compromise patient safety. [Nielsen S, Bruno R, Degenhardt L, Demirkol A, Lintzeris N. Opioid agonist doses for oxycodone and morphine dependence: Findings from a retrospective case series Drug Alcohol Rev 2017;36:311-316].

Topics: Adult; Analgesics, Opioid; Buprenorphine; Dose-Response Relationship, Drug; Female; Humans; Male; Methadone; Middle Aged; Morphine Dependence; Opiate Substitution Treatment; Opioid-Related Disorders; Oxycodone; Retrospective Studies

The method of choice for reversal of opioid-toxicity is administration of naloxone. This treatment can be accompanied by complications including acute lung-injury, myocardial infarction, or withdrawal-syndrome (in dependent-patients). We aimed to evaluate the efficacy of buprenorphine in reversal of opioid-overdose syndrome in dependent-rats. A prospective case-control study was designed, in which a total of 30 rats were put on opioid-dependency protocol with 10 mg/kg of intra-peritoneal morphine twice daily for 10 days. After confirmation of dependency by naloxone administration, the rats were overdosed by giving 16 mg/kg of intra-peritoneal methadone. They were divided into four groups receiving naloxone (n=7; 2 mg/kg) and buprenorphine(n=8, 8, and 7 with doses of 3 mg/kg, 6 mg/kg, and 10 mg/kg), respectively. These four groups were compared regarding reversal of opioid signs/symptoms and development of withdrawal-syndrome. Rats in the first group showed signs/symptoms of opioid-withdrawal severely and with a higher frequency (P<0.001). In the groups 2-4, all doses recovered the intoxicated-rats without inducing signs/symptoms of withdrawal; however, the 3mg/kg dose reversed toxicity slower (P<0.001) and one rat in this group died later due to the re-development of signs of toxicity. Buprenorphine recovers opioid-overdose in morphine-dependent rats and bypasses the withdrawal-syndrome due to administration of naloxone.

Topics: Animals; Buprenorphine; Drug Overdose; Male; Methadone; Morphine Dependence; Naloxone; Narcotic Antagonists; Rats; Rats, Wistar

It is considered that a long-acting therapy would be advantageous in the treatment of addiction. In a search for novel buprenorphine analogues, thienorphine was demonstrated to be an extremely long-acting orally active partial opioid agonist. This study explored the mechanisms underlying the long-lasting effects of thienorphine.. The binding kinetics of [(3) H]thienorphine were measured in membrane preparations expressing cloned rat opioid receptors. Flow cytometric analysis was used to determine the effect of thienorphine on the surface opioid receptor number. The long-lasting effects of thienorphine were also confirmed at the tissue level and in vivo.. At 37°C, [(3) H]thienorphine showed rapid association with μ- and κ-opioid receptors, while its dissociation was sluggish and biphasic (K-1 = 0.21 min(-1) , K-2 = 0.0078 min(-1) for the μ-receptor; K-1 = 0.17 min(-1) , K-2 = 0.0042 min(-1) for the κ-receptor). Treatment with thienorphine for 24, 48, and 72 h downregulated surface μ-receptor in a dose- and time-dependent manner. The inhibitory effect of thienorphine on guinea pig ileum persisted for more than 120 min after prolonged washing. In vivo, thienorphine exhibited significant antagonism of morphine-induced antinociception for more than 7 days.. These results indicate that multiple factors, including persistent receptor occupation and enhanced receptor downregulation, may contribute to the long-lasting effects of thienorphine that would be beneficial for its application in addiction treatment.

Topics: Acetylcholine; Animals; Buprenorphine; Cell Line, Transformed; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Guinea Pigs; Ileum; Male; Mice; Mice, Inbred Strains; Morphine Dependence; Muscle Contraction; Narcotic Antagonists; Protein Binding; Rats; Receptors, Opioid; Time Factors; Tritium

A combination of polytetrafluorethylene membrane-based liquid three-phase micro-extraction and voltammetry was used for the micro-separation and determination of buprenorphine. Type of the organic solvent used, pH levels of the donor and acceptor phases, salt concentration, extraction time, stirring rate, and electrochemical parameters as the essential factors affecting the liquid three-phase micro-extraction of buprenorphine were investigated. Differential pulse voltammetry exhibited two linear dynamic ranges of 1.0-109.0 pmol L(-1) and 0.109 nmol L(-1)-0.11 µmol L(-1) of buprenorphine and the detection limit was found to be as low as 0.6 pmol L(-1) of buprenorphine. Also, the effects of a number of common substances potentially interfering with selectivity were studied. The results indicate that the proposed method is highly selective and sensitive for buprenorphine detection in real samples such as human urine and plasma of both drug-addict and non-addict human subjects.

Topics: Buprenorphine; Calibration; Electrochemical Techniques; Electrodes; Graphite; Humans; Hydrogen-Ion Concentration; Limit of Detection; Liquid Phase Microextraction; Membranes, Artificial; Morphine Dependence; Narcotics; Polytetrafluoroethylene; Sodium Chloride; Solvents

Abuse of addictive substances is a serious problem that has a significant impact on areas such as health, the economy, and public safety. Heroin use among young women of reproductive age has drawn much attention around the world. However, there is a lack of information on effects of prenatal exposure to opioids on their offspring. In this study, an animal model was established to study effects of prenatal exposure to opioids on offspring.. Female pregnant Sprague-Dawley rats were sub-grouped to receive (1) vehicle, (2) 2-4 mg/kg morphine (1 mg/kg increment per week), (3) 7 mg/kg methadone, and (4) 3 mg/kg buprenorphine, subcutaneously, once or twice a day from E3 to E20. The experiments were conducted on animals 8-12 weeks old and with body weight between 250 and 350 g.. Results showed that prenatal exposure to buprenorphine caused higher mortality than other tested substance groups. Although we observed a significantly lower increase in body weight in all of the opioid-administered dams, the birth weight of the offspring was not altered in all treated groups. Moreover, no obvious behavioral abnormality or body-weight difference was noted during the growing period (8-12 weeks) in all offspring. When the male offspring received morphine injection twice a day for 4 days, the prenatally opioid-exposed rats more quickly developed a tolerance to morphine (as shown by the tail-flick tests), most notably the prenatally buprenorphine-exposed offspring. However, the tolerance development to methadone or buprenorphine was not different in offspring exposed prenatally to methadone or buprenorphine, respectively, when compared with that of the vehicle controlled group. Similar results were also obtained in the female animals.. Animals prenatally exposed to morphine, methadone, or buprenorphine developed tolerance to morphine faster than their controlled mates. In our animal model, prenatal exposure to buprenorphine also resulted in higher mortality and much less sensitivity to morphine-induced antinociception than prenatal exposure to morphine or methadone. This indicates that buprenorphine in higher doses may not be an ideal maintenance drug for treating pregnant women. This study provides a reference in selecting doses for clinical usage in treating pregnant heroin addicts.

Topics: Analgesics; Animals; Buprenorphine; Disease Models, Animal; Drug Tolerance; Female; Heroin Dependence; Humans; Male; Methadone; Morphine; Morphine Dependence; Pain Measurement; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley

Buprenorphine is a promising new pharmacotherapy for the management of physical dependence to opioids. The aim of the study was to evaluate the duration of action of several novel depots of buprenorphine in the treatment of physical dependence to morphine in mice. Following intramuscular injection, the duration of action of several novel oil-based depots of buprenorphine base in morphine-dependent mice were evaluated. The traditional dosage form of buprenorphine hydrochloride in saline was used as control. We found that the depot of buprenorphine base in sesame oil produced a dose-related long-lasting effect. On an equimolar basis of 6 micromol kg(-1), its effect was 5.7-fold longer than that of buprenorphine hydrochloride in saline. When prepared in several other oleaginous vehicles (castor oil, cottonseed oil, peanut oil and soybean oil), buprenorphine base also produced a long-lasting effect, which was similar to buprenorphine base in sesame oil. In conclusion, buprenorphine base, when prepared in oleaginous vehicles and injected intramuscularly in mice, produced a long-lasting effect on physical dependence to morphine.

Topics: Animals; Buprenorphine; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Implants; Male; Mice; Morphine Dependence; Narcotic Antagonists; Sesame Oil

The purpose of this study was the evaluation of clinical heroin symptoms and buprenorphine drug addiction in the withdrawal period with the purpose of their comparison, study of parameters of bone metabolism in the both groups. In the study group were included 40 patients with heroin and 27 with buprenorphine addiction in the period of abstinence. Our investigations have shown, that in the both groups, among clinical symptoms ossalgias, arthralgias and mialgias attributes to the expressed dysfunction of vegetative system, were most prominent. Decrease of sexual functions was found in half of inspected patients. Biochemical investigations have shown intensive clearance of calcium with the urine that indicates intensifying resorbtion processes in the bone tissue. Symptoms of hypogonadism were accompanied by the decrease of the level of testosterone in the blood. Parameters of mineral consistency of the bone tissue was decreased both in patients with heroin and buprenorphine addiction.

Topics: Behavioral Symptoms; Biomarkers; Bone and Bones; Bone Density; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Male; Morphine Dependence; Pain; Radiography; Substance Withdrawal Syndrome

Infants placed on extracorporeal membrane oxygenation (ECMO) or mechanical ventilation often need continuous morphine infusions for pain relief and sedation. The resulting physical dependence requires an additional 2-3-week hospital stay to taper the morphine to avoid withdrawal. Buprenorphine effectively blocks abstinence in dependent adults, and in infants it could accelerate or eliminate the tapering schedule, thereby enabling earlier hospital dismissals.. Morphine-dependent infant rats were used in this study to determine the effectiveness of buprenorphine in blocking abstinence. Postnatal day-14 (P14) rats were implanted with osmotic minipumps that delivered saline (1 microl x h(-1)) or morphine (2 mg x kg(-1) h(-1)) for 72 h. The minipumps were then removed to allow the rats to undergo spontaneous morphine withdrawal.. The withdrawal period lasted approximately 72 h out of a 96-h observation period. The following signs were significant during these hours: wet-dog shakes, 1-72 h; abdominal stretches, 1-72 h; forepaw tremors, 1-24 h; splayed hind-limbs, 1-72 h; ptosis, 4-72 h; and evoked vocalization, 4 and 8 h. A single 1 mg x kg(-1) buprenorphine dose significantly decreased wet-dog shakes from 1 to 72 h, abdominal stretches from 1 to 48 h, forepaw tremors and splayed hind-limbs 1-8 h, and ptosis and evoked vocalization at 4 and 8 h. Repeated administration of 1 mg x kg(-1) buprenorphine before pump removal and at 24, 48 and 72 h resulted in a greater magnitude of blockade of abstinence throughout the 96-h observation period.. Buprenorphine may prove to be a suitable drug for treating opioid withdrawal in human infants.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Male; Morphine; Morphine Dependence; Rats; Rats, Sprague-Dawley; Sodium Chloride; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome

The effects of buprenorphine (0.0125-0.2 mg kg(-1)) on the locomotor activity of rats were determined 1-2 months after ceasing a chronic treatment with morphine (20 mg kg(-1)for 28 days). In control animals buprenorphine exhibited both depressive and stimulatory actions, as repeatedly described for morphine. In post-dependent animals buprenorphine showed a depressive effect similar to that observed in naive ones. On the contrary, a persistent sensitization to the excitatory effect was observed; the degree of cross-sensitization was similar to that of morphine itself (20 mg kg(-1)). The results are discussed in terms of persistent changes in the locomotor response to opioids, possibly correlated to both drug craving and relapse.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Male; Morphine; Morphine Dependence; Motor Activity; Narcotics; Rats

Withdrawal of opiates drug addicts in Internal Medicine is unusual in France. Four main preliminary conditions are requested: 1--Drug addict preparation and self motivation, 2--Inter and intra institution team collaboration, 3--Opening the hospital towards community agencies, 4--Hospital staff recruited on volunteer basis. Within two years (1992-1993), 210 opiates drug addicts were hospitalized for withdrawal. Two third were males, median age was 27, median years of addiction was 7. Thirty percent were seropositive for HIV, 70% for HCV. Hospitalisation lasted 7 days for heroin addicts and 10 days for morphin, codein or buprenorphin addicts. Successful withdrawn was observed for 70% patients but six months after withdrawal, only 15% remained abstinent.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Codeine; Female; France; Heroin Dependence; Hospital Departments; Hospitalization; Humans; Internal Medicine; Male; Morphine Dependence; Opioid-Related Disorders; Recurrence; Time Factors

This study was conducted to characterize the opiate dependence potential of a number of opiate and non-opiate psychoactive drugs in morphine-dependent cynomolgus monkeys (Macaca fascicularis). In addition, the agonist/antagonist profiles of buprenorphine and butorphanol were directly compared. Six male cynomolgus monkeys were maintained on morphine (3.0 mg/kg, q.i.d.) for 6 months. On evaluation days, monkeys were scored for opiate withdrawal signs 18 h after the last dose of morphine. Single dose suppression studies were conducted by giving subcutaneous injections of morphine (3 or 6 mg/kg), naloxone (0.01, 0.05 or 0.1 mg/kg), buprenorphine (1, 3, 10, 30 or 100 micrograms/kg), butorphanol (0.01, 0.1, 1.0 or 3.2 mg/kg), haloperidol (0.01, 0.05 or 0.1 mg/kg), imipramine (2, 5 or 10 mg/kg) or saline and measuring the number and frequency of withdrawal signs that appeared over a 2-h period. In a separate precipitation experiment either saline or 0.01 or 0.1 mg/kg butorphanol was administered 2 h after the last maintenance dose of morphine. In the single dose suppression test, morphine completely suppressed most withdrawal signs while naloxone increased the severity of withdrawal. All doses of buprenorphine increased many withdrawal signs such as backward gait, rearing, chafing face, chain biting, vomiting, masturbation, and vocalizations after intimidation. Only a few signs were reduced, but the overall withdrawal scores were not significantly increased. Low doses of butorphanol suppressed some signs while the highest dose almost completely eliminated all withdrawal signs. Butorphanol also failed to precipitate opiate withdrawal, and actually reversed the signs present in the saline-treated monkeys. Imipramine and haloperidol had little effect on the morphine withdrawal syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Behavior, Animal; Buprenorphine; Butorphanol; Haloperidol; Imipramine; Macaca fascicularis; Male; Morphine; Morphine Dependence; Naloxone; Psychotropic Drugs; Substance Withdrawal Syndrome

The effects of buprenorphine (0.01-0.1 mg/kg) on the activity of nondependent and morphine dependent rats (a 20 mg/kg dose for 28 days) were determined. In naive animals buprenorphine exhibited both depressive and stimulatory actions upon the motility of rats, as repeatedly described for morphine. When buprenorphine was administered to rats chronically treated with morphine, the depressive effect disappeared (cross-tolerance to the inhibitory action); on the contrary the excitatory effect was enhanced (cross-sensitization). The results are discussed in terms of cross-sensitization to the excitatory effects in morphine dependent animals as predictor of morphine-like addictive properties in humans.

Topics: Animals; Buprenorphine; Male; Morphine; Morphine Dependence; Motor Activity; Rats; Rats, Sprague-Dawley

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.

Topics: Adult; Buprenorphine; Cross-Sectional Studies; Drug Combinations; Female; Heroin Dependence; Humans; Incidence; Male; Morphine Dependence; Naloxone; New Zealand; Substance Abuse Detection; Substance-Related Disorders

Buprenorphine is a mixed opioid agonist/antagonist which appears to produce less physical dependence and respiratory depression than typical mu-agonist opioids. These effects suggest its use for analgesia for drug abusers. However, buprenorphine may precipitate withdrawal from other opioids. The present case illustrates the utility of buprenorphine and describes a method to transfer a patient from a mu-agonist to buprenorphine without precipitating withdrawal or interrupting analgesia.

Topics: Adult; Buprenorphine; Crohn Disease; Drug Administration Schedule; Humans; Male; Morphine; Morphine Dependence; Naloxone; Neurologic Examination; Pain; Pain Measurement; Single-Blind Method; Substance Withdrawal Syndrome

1. Doses of buprenorphine (0.01, 0.1, 0.5, 1, 5, 10 and 50 mg/kg) were administered to determine buprenorphine's ability to precipitate abstinence symptoms in morphine-dependent mice. 2. When buprenorphine was administered in the fourth day of morphine addiction, the results demonstrate that the administration of the partial agonist opioid produce a bell-shaped dose-response curve. 3. The highest dose (50 mg/kg) was partially inactive while lower doses causing similar percentage than group treated with naloxone with respect to the appearance of the most of the symptoms of abstinence studied (diarrhoea, tremor, shaking-"wet dog shakes"-, jumping and weight loss). 4. Our findings demonstrate the bell-shaped response curve of the antagonist effects of buprenorphine.

Topics: Animals; Behavior, Animal; Buprenorphine; Diarrhea; Dose-Response Relationship, Drug; Male; Mice; Mice, Inbred Strains; Morphine Dependence; Naloxone; Substance Withdrawal Syndrome; Tremor

The mixed agonist-antagonist analgesics buprenorphine, butorphanol, nalbuphine, pentazocine and picenadol were compared to the prototype mu and kappa agonists morphine and Mr 2033, respectively, in the following tests in rhesus monkeys: overt behavioral effects upon acute administration in drug-naive animals; discriminative stimulus properties in monkeys trained to respond to either etorphine or ethylketazocine; self-administration of the test agent relative to codeine; single dose suppression and precipitation in withdrawn and non-withdrawn morphine-dependent monkeys, respectively; and primary addiction studies in drug-naive animals. Whereas both buprenorphine and nalbuphine precipitate withdrawal in morphine-dependent monkeys, withdrawal following chronic administration of buprenorphine resulted in no observable signs of abstinence, while nalbuphine withdrawal was similar to that seen in morphine-dependent monkeys. Butorphanol, pentazocine and picenadol all produced mild dependence of the kappa-type; that is, natural withdrawal behavior similar to that seen following chronic Mr 2033 administration.

Topics: Animals; Behavior, Animal; Benzomorphans; Buprenorphine; Butorphanol; Codeine; Discrimination, Psychological; Humans; Macaca mulatta; Morphinans; Morphine; Morphine Dependence; Nalbuphine; Narcotic Antagonists; Pentazocine; Piperidines; Substance Withdrawal Syndrome

In non-withdrawn maximally-dependent rhesus monkeys, both naloxone (NOX) and nalorphine (NAL) precipitated withdrawal when given 2 h after morphine (M). When these drugs were given 15 h after M, at which time the animals were in severe withdrawal and M blood levels were much lower, they promptly exacerbated withdrawal. Thus, mu antagonists may act competitively in non-withdrawn addicts and noncompetitively in withdrawn subjects. Buprenorphine (BRN), the partial mu agonist, precipitated withdrawal in stable addicts and partly suppressed withdrawal signs in abstinent addicts. Finally, ethyl-ketocyclazocine (EKC), the purported kappa agonist, did not precipitate but partly suppressed withdrawal at doses producing severe side effects. Perhaps this suppression is associated with kappa activity.

Topics: Animals; Buprenorphine; Cyclazocine; Ethylketocyclazocine; Humans; Macaca mulatta; Morphine Dependence; Naloxone; Narcotic Antagonists; Narcotics; Receptors, Opioid; Receptors, Opioid, mu; Substance Withdrawal Syndrome

The capacity of morphine to suppress natural and precipitated withdrawal was compared in morphine-dependent rhesus monkeys. A similar severity of withdrawal was induced by 14-hr deprivation or precipitated by naloxone, naltrexone, cyclazocine, Win 44,441 or MR 2266. Regardless of the procedure used to induce withdrawal, behavioral signs were completely suppressed by a cumulative dose of 17.5 mg/kg morphine. Thus, an equivalent level of withdrawal induced by reversible antagonists is as sensitive to subsequent morphine administration as is deprivation-induced abstinence. This is in accordance with the theory that vacancy of opiate receptors normally occupied by morphine is related to the level of abstinence observed. In contrast to Win 44,441, however, an equivalent level of withdrawal precipitated by buprenorphine required 175 mg/kg morphine for complete suppression. This is more informative than comparing duration of action; when given as 24-h pretreatments, a high dose of Win 44,441 (10 mg/kg) was only slightly less effective than buprenorphine (3.2 mg/kg) in antagonizing morphine-induced stupor in normal monkeys. Comparison of the ability of morphine to suppress precipitated withdrawal provides evidence of the relative reversibility of antagonists in vivo and demonstrates the extraordinarily stable nature by which buprenorphine acts at opiate receptors.

Topics: Animals; Behavior, Animal; Buprenorphine; Humans; Macaca mulatta; Morphine; Morphine Dependence; Narcotic Antagonists; Receptors, Opioid; Substance Withdrawal Syndrome

The ability of four opiate partial agonists (buprenorphine, xorphanol, nalbuphine and butorphanol) to produce antinociception and morphine-like physical dependence was examined in the rat. For comparative purposes, morphine was also tested. Dose-response curves were constructed using the rat tail pressure test for analgesia which indicated a rank order of potency of buprenorphine much greater than morphine greater than butorphanol greater than xorphanol = nalbuphine. Assessment of primary physical dependence liability was made using the technique of chronic intraperitoneal infusion followed by precipitation of abstinence with the opiate antagonist, naloxone. The results clearly indicate that buprenorphine was not only the most potent antinociceptive agent, but also possessed the lowest incidence of physical dependence as indicated by precipitated abstinence signs. The other opiates were very much weaker as antinociceptive agents and all produced clear signs of physical dependence.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Butorphanol; Humans; Male; Morphinans; Morphine; Morphine Dependence; Nalbuphine; Nociceptors; Rats; Rats, Inbred Strains

Topics: Buprenorphine; Cyclazocine; Humans; Methadone; Morphinans; Morphine Dependence; Naltrexone