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At least 19 recordsLinked to original sources
PubMed2003

Heroin maintenance for chronic heroin dependents.

BACKGROUND: Dependent heroin users are characterised by the persistence of use in spite of the difficulties they experience with health, law, social achievements and personal relationships. The present review will consider maintenance treatment in which the patients enter programs of pharmacological administration tailored to achieve patient stabilisation. Many medications have been used for this purpose such as: Methadone, Buprenorphine and LAAM. The present review will focus on maintenance treatment through the prescription of heroin. OBJECTIVES: To assess the efficacy and acceptability of heroin maintenance versus methadone or other substitution treatments for opioid dependence, in retaining patients in treatment; reducing the use of illicit substances and improving health and social functioning. SEARCH STRATEGY: The Cochrane Central Register of Trials (CENTRAL) issue 4, 2002; MEDLINE (on Silver Platter) 1966-2002; EMBASE (on OVID) 1980-2000 and CINAHL till 2000 were searched. There was no language or publication year restrictions. Many researchers were contacted for information. SELECTION CRITERIA: Randomised controlled trials of heroin (alone or combined with methadone) maintenance treatment compared with any other pharmacological treatments. DATA COLLECTION AND ANALYSIS: The trials were independently assessed for inclusion and methodological quality by the reviewers. Data were extracted independently and double checked. Studies were not pooled together because of heterogeneity. MAIN RESULTS: 2400 references were obtained and 20 studies were eligible, 4 met the inclusion criteria for a total of 577 patients. The studies included could not be analysed cumulatively because of heterogeneity of interventions and outcomes considered. Two studies compared injected heroin to oral methadone for 1 year (270 patients) but considered different outcomes; one study compared injected heroin and methadone to oral methadone for 6 months (51 patients); and one compared inhaled heroin and methadone to oral methadone for 1 year (235 patients). Retention in treatment: in two studies there was no statistical difference between groups; one study (N=90) had a RR=2.49 (95% CI 1.51-4.10) in favour of heroin; one study (N=235) had a RR 0.79 (95%CI 0.68-0.90) in favour of methadone. Relapse to illegal heroin use, based on self report: in one study the proportion of people still using heroin were 64% in the heroin group, 59% methadone group; in the other study the RR was 0.33 (95%CI 0.15-0.72) in favour of heroin. The remaining studies did not provide the data. Criminal offence: one of the two studies which provided details about this showed the potential of heroin prescription in reducing the risk of being charged RR 0.32 (95% CI 0.14-0.78). Social functioning: the two studies reporting this outcome did not show statistical difference between intervention groups. The two most recent studies considered criminal offence and social functioning as part of a multidomain outcome measure and showed higher improvement among those treated with heroin plus methadone over those on methadone only. REVIEWER'S CONCLUSIONS: No definitive conclusions about the overall effectiveness of heroin prescription is possible because of non-comparability of the experimental studies available to be included in this review. Results favouring heroin treatment come from studies conducted in countries where the treatment system is comprehensive and easy accessible Methadone Maintenance Treatment at effective dosages is available. In those studies heroin prescription was addressed to patients who had failed previous methadone treatments.

Heroin↗
PubMed2003

Smoked heroin in rhesus monkeys: effects of heroin extinction and fluid availability on measures of heroin seeking.

The purpose of the present study was to evaluate the reinforcing effects of smoked heroin in nonopioid-dependent nonhuman primates when an alternative reinforcer, sweetened fluid, was made available. Four adult male rhesus monkeys lived in three chambers, with heroin self-administration (0, 0.3, and 0.6 mg/kg) specific to one end of the chamber, oral sweetened fluid self-administration specific to the other end chamber, and no commodity available in the middle chamber. The length of time monkeys spent in the drug-associated chamber provided one measure of drug seeking (i.e., location preference). During self-administration sessions, a second-order schedule of reinforcement was used, with responding during the first component maintained by a brief presentation of the stimuli associated with reinforcement. Responding during the second component was maintained by a delivery of the reinforcer, and the associated stimuli. Responding during the first component provided a second measure of drug seeking. Monkeys also had choice trials each day, when they could choose to work for either commodity. Choice behavior provided a third measure of drug seeking. Each experimental day consisted of a smoking session (four smoking trials), a sweetened fluid session (four fluid trials), and a choice session (four choice trials). Monkeys typically completed all four smoking trials each day when either of the active heroin doses was available. They chose both heroin doses over fluid on 3.5 of the four choice trials, and they had a location preference for the heroin chamber. Under baseline conditions, the number of acquisition responses and the number of consumption responses (inhalations) were greater for the high dose of heroin compared to the low dose of heroin. Further, it took longer to extinguish the responding for the high dose of heroin compared to the low dose of heroin when a vehicle was substituted. During heroin extinction, acquisition responding for fluid increased, the number of fluid choices increased, and location preference shifted to the fluid chamber. These data suggest that in nondependent rhesus monkeys, measures of heroin seeking decreased when heroin was not available and seeking behavior shifted to the available alternative commodity.

Animals↗
PubMed2006

Heroin-induced reinstatement is specific to compulsive heroin use and dissociable from heroin reward and sensitization.

Increased drug availability can precipitate a rapid transition to compulsive drug use in both vulnerable humans and laboratory animals. Recent studies have shown that despite equivalent levels of psychomotor sensitization, only rats with prolonged, but not limited, access to cocaine self-administration respond to the priming effects of cocaine on drug seeking, as measured in a within-session reinstatement model of drug craving. In this model, drug seeking is first extinguished and then reinstated by non-contingent presentations of the drug alone in the absence of response-contingent stimuli. Here, we assessed the generality of this observation in rats with daily short (1 h, ShA) vs long access (6 h, LgA) to i.v. heroin self-administration. As expected, heroin intake by LgA rats (n=24) increased over time to become excessive compared to heroin intake by ShA rats (n=24). After escalation, LgA rats tended to be less sensitive to heroin-induced locomotion (7.5-30 microg, i.v.) than ShA rats. In contrast, only LgA rats, not ShA rats, responded to the priming effects of heroin, as measured by the ability of heroin alone (7.5-30 microg, i.v.) to reinstate extinguished drug-seeking behavior. Finally, during the course of heroin intake escalation, a large proportion of LgA rats developed self-injury (mostly targeting the nails and digit tips of the forepaws), a negative consequence not seen in ShA rats. This study reproduces and extends previous research on compulsive cocaine use by showing that heroin-induced reinstatement is also specific to compulsive drug use and dissociable from heroin-induced reward and psychomotor sensitization.

Animals↗
PubMed1994

Transitions in patterns of heroin administration: a study of heroin chasers and heroin injectors.

A community sample of 408 heroin users was interviewed about changes in their predominant route of heroin administration. Clear preferences for specific routes of drug administration were evident. Two predominant routes of administration were found: injection (54%) and 'chasing the dragon' (44%). More than a third of the sample had changed their predominant route of administration (a 'transition'). Most commonly, only one transition was reported, from chasing to injecting. However, transition to injection was not inevitable: the majority of 'chasers' had never moved to regular injecting despite often using at high doses for many years. Modelling suggests that many chasers give up heroin without moving to injecting. The results indicate, however, a continuing risk of switching from chasing to injecting for those who continued to use. Women were less likely to move from chasing to injecting. Some heroin users had made the transition from injection to chasing; 28 (16%) of the current chasers had previously been regular heroin injectors. This change in route is less well-known and to our knowledge has not been previously investigated. Multiple transitions in route were uncommon; predominant route of administration, once established appears robust. Harm reduction interventions directed towards changing the risk behaviours of heroin users should take account of the different routes of current administration and the potential for future transitions within continued drug use.

Administration, Inhalation↗
PubMed2000

Heroin self-administration under a second-order schedule of reinforcement: acquisition and maintenance of heroin-seeking behaviour in rats.

RATIONALE: Second-order schedules of heroin self-administration provide a method of measuring heroin-seeking behaviour independently of the effects of the drug on motor behaviour and of investigating the role of heroin-associated stimuli in such heroin-seeking behaviour. OBJECTIVES: These experiments aimed to establish a second-order schedule of heroin self-administration in rats, similar to that already established in this laboratory for cocaine self-administration and to investigate the role of discrete heroin-associated stimuli in the maintenance of heroin-seeking behaviour under a second-order schedule of reinforcement. METHODS: Heroin i.v. self-administration (0.04 mg/infusion) was initially contingent upon a lever press, and each infusion was paired with presentation of a 20-s light-conditioned stimulus (CS). Following acquisition of heroin self-administration, the response requirement was progressively increased so that, ultimately, responding was maintained under a fixed interval (FI) 15 min [fixed ratio (FR)5:S] second-order schedule. The effects of varying the dose of heroin (0.01 mg and 0.08 mg/infusion) and pre-treatment with the mu-opiate receptor antagonist, naloxone, on responding under a FI15(FR5:S) schedule were investigated. In addition, the role of the heroin-associated CS on responding was assessed by measuring the effects of omitting the CS during heroin-seeking behaviour and during extinction of responding, as well as the effect of CS presentation on the reinstatement of heroin-seeking behaviour following extinction. RESULTS: A second-order schedule of heroin self-administration was established. There were no clear effects on heroin-seeking behaviour of increasing or decreasing the dose of heroin. Although no effect of naloxone pre-treatment was seen on heroin-seeking behaviour during the first, drug-free interval of responding, an extinction-like pattern of responding was seen in that interval during subsequent sessions. Omission of the light CS resulted in a reduction in levels of responding for i.v. heroin, indicating its role in maintaining heroin-seeking behaviour. However, under extinction conditions, response-contingent CS presentations did not affect the rate of extinction, nor did non-contingent presentations of the CS following extinction reinstate heroin-seeking behaviour. CONCLUSIONS: These experiments have established a method of measuring heroin-seeking behaviour in rats by adopting a second-order schedule of i.v. heroin self-administration. The results indicate a relatively weak impact of discrete, heroin-associated cues on heroin-seeking behaviour relative to cocaine-seeking behaviour studied under similar conditions.

Animals↗
PubMed2006

Changes in the initiation of heroin use after a reduction in heroin supply.

Increasing heroin use in Australia over the past 30 years has been associated with a decline in the age of initiation to heroin use. The 2001 Australian heroin shortage was used to assess the effects of a reduction in heroin supply on age of initiation into heroin injecting. Data collected from regular injecting drug users (IDU) over the period 1996 - 2004 as part of the Australian Illicit Drug Reporting System were examined for changes in self-reported age of first heroin use after the onset of the heroin shortage. Estimates were also made of the number of young people who may not have commenced injecting heroin during the heroin shortage. The proportion of IDU interviewed in the IDRS who were aged <or=24 years decreased from 46% in 1996 to 12% in 2004, with the most marked drop in 2001, the year in which there was an abrupt and marked reduction in heroin availability. Of those who reported first injecting between 1993 and 2000, similar proportions reported heroin and amphetamine as the first drug injected. After 2000, methamphetamine was the drug most often reported as being the first injected. Estimates suggested that between 2745 and 10,560 young people may not have begun to inject heroin in 2001 as a result of reduced heroin supply. If around one in four of these young users had progressed to regular or dependent heroin use, then there may have been a reduction of between 700 and 2500 dependent heroin users. There was an increase in amphetamine injecting but it is unclear to what extent any reduction in heroin injecting has been offset by increased amphetamine injecting. Reduced heroin availability probably resulted in a reduction in the number of new heroin injectors in Australia. Efforts need to be made to reduce the chances that young people who have initiated methamphetamine injecting do not move to heroin injecting when the heroin supply returns.

Adolescent↗
PubMed2005

Initiation to heroin injecting among heroin users in Sydney, Australia: cross sectional survey.

BACKGROUND: Heroin injection is associated with health and social problems including hepatitis C virus (HCV) transmission. Few studies have examined the circumstances surrounding initiation to heroin injecting, especially current users initiating others. The current study aimed to examine the age of first heroin use and injection; administration route of first heroin use; relationship to initiator; the initiation of others among a group of heroin users; and to examine these factors in relation to HCV status and risk. METHOD: Heroin users in Sydney were recruited through needle and syringe programs, a methadone clinic and snowballing. Participants were interviewed about their own initiation to heroin use, blood-borne virus risk and knowledge, and whether they had initiated others to heroin injecting. Information on HCV status was collected via self-report. Data was analysed using univariate and multivariate statistical techniques for Normally distributed continuous and categorical data. RESULTS: The study recruited 399 heroin users, with a mean age of 31 years, 63% were male, 77% reported heroin as their primary drug and 59% were HCV positive (self-report). Mean age at first heroin use and injection was 19 and 21 years, respectively. The majority of heroin users commenced heroin use via injecting (65%), younger users (<25 years, 25-30 years) were less likely than older users (>30 years) to commence heroin use parenterally. Participants were initiated to injection mainly by friends (63%). Thirty-seven percent reported initiating others to heroin injection, but few factors were related to this behaviour. Those with longer heroin using careers were more likely to report initiating others to heroin injection, but were no more likely to have done so in the preceding 12 months. Participants who had initiated others were more likely to have shared injecting equipment (12 vs 23%), but were no more likely to be HCV positive (self-report) than those who did not. CONCLUSION: Interventions to prevent heroin users initiating others to injecting are necessary. Peer groups may be well positioned to implement such interventions.

Journal Article↗
PubMed2005

Heroin maintenance for chronic heroin dependents.

BACKGROUND: Many medications have been used for stabilizing heroin users: Methadone, Buprenorphine and LAAM. The present review focus on the prescription of heroin to heroin dependents. OBJECTIVES: To assess the efficacy and acceptability of heroin maintenance versus methadone or other substitution treatments for opioid dependence, in retaining patients in treatment; reducing the use of illicit substances and improving health and social functioning. SEARCH STRATEGY: The Cochrane Central Register of Trials (CENTRAL) issue 1, 2005; MEDLINE 1966-2005, EMBASE 1980-2005 and CINAHL till 2005 (on OVID) were searched. There was no language or publication year restrictions. Many researchers were contacted for information. SELECTION CRITERIA: Randomised controlled trials of heroin (alone or combined with methadone) maintenance treatment compared with any other pharmacological treatments for heroin dependents. DATA COLLECTION AND ANALYSIS: The trials were independently assessed for inclusion and methodological quality by the reviewers. Data were extracted independently and double checked. Studies were not pooled together because of heterogeneity. MAIN RESULTS: 2400 references were obtained and 20 studies were eligible, 4 met the inclusion criteria for a total of 577 patients. The studies could not be analysed cumulatively because of heterogeneity of interventions and outcomes. Retention in treatment: no groups difference was found in two studies; one study (N=96) found RR=2.82 (95% CI 1.70-4.68) favouring heroin; one study (N=235) found RR 0.79 (95%CI 0.68-0.90) favouring methadone. Relapse to illegal heroin use (self- reported): in one study people using heroin in treatment was 64% (heroin group)and 59% (methadone group); in the other study the RR of heroin use was 0.33 (95%CI 0.15-0.72) favouring heroin. Criminal offence: one study showed the potential of heroin prescription in reducing the risk of being charged RR 0.32 (95% CI 0.14-0.78). Social functioning: two studies did not show statistical difference between intervention groups, and two studies considered criminal offence and social functioning as part of a multidomain outcome measure showing improvements among those treated with heroin plus methadone over those on methadone only. AUTHORS' CONCLUSIONS: No definitive conclusions about the overall effectiveness of heroin prescription is possible. Results favouring heroin treatment come from studies conducted in countries where easily accessible Methadone Maintenance Treatment at effective dosages is available. In those studies heroin prescription was addressed to patients who had failed previous methadone treatments. The present review contains information about ongoing trials which results will be integrated as soon as available.

Heroin↗
PubMed2006

Changes in Canadian heroin supply coinciding with the Australian heroin shortage.

AIMS: Previous studies have largely attributed the Australian heroin shortage to increases in local law enforcement efforts. Because western Canada receives heroin from similar source nations, but has not measurably increased enforcement practices or funding levels, we sought to examine trends in Canadian heroin-related indices before and after the Australian heroin shortage, which began in approximately January 2001. METHODS: During periods before and after January 2001, we examined the number of fatal overdoses and ambulance responses to heroin-related overdoses that required the use of naloxone in British Columbia, Canada. As an overall marker of Canadian supply reduction, we also examined the quantity of heroin seized during this period. Lastly, we examined trends in daily heroin use among injection drug users enrolled in the Vancouver Injection Drug Users Study (VIDUS). RESULTS: There was a 35% reduction in overdose deaths, from an annual average of 297 deaths during the years 1998-2000 in comparison to an average of 192 deaths during 2001-03. Similarly, use of naloxone declined 45% in the period coinciding with the Australian heroin shortage. Interestingly, the weight of Canadian heroin seized declined 64% coinciding with the Australian heroin shortage, from an average of 184 kg during 1998-2000 to 67 kg on average during 2001-03. Among 1587 VIDUS participants, the period coinciding with the Australian heroin shortage was associated independently with reduced daily injection of heroin [adjusted odds ratio: 0.55 (95% CI: 0.50-0.61); P < 0.001]. CONCLUSIONS: Massive decreases in three independent markers of heroin use have been observed in western Canada coinciding with the Australian heroin shortage, despite no increases in funding to Canadian enforcement efforts. Markedly reduced Canadian seizure activity also coincided with the Australian heroin shortage. These findings suggest that external global heroin supply forces deserve greater investigation and credence as a potential explanation for the Australian heroin shortage.

Australia↗
PubMed2004

Exposure to delta-9-tetrahydrocannabinol (THC) increases subsequent heroin taking but not heroin's reinforcing efficacy: a self-administration study in rats.

One concern about the widespread use of cannabis is that exposure to its active ingredient, delta-9-tetrahydrocannabinol (THC), might increase future reinforcing effects of other abused drugs such as heroin. In this study, we investigated the effects of pre-exposure to THC on subsequent intravenous self-administration of heroin by Sprague-Dawley rats. In one group of rats, we studied (1) acquisition of heroin self-administration behavior using a continuous-reinforcement (fixed-ratio (FR) 1) schedule, (2) heroin dose-response relationships using an FR1/variable-dose schedule, and (3) reinforcing efficacy of heroin using a progressive-ratio schedule. The number of rats pre-exposed to THC that subsequently learned to self-administer 50 microg/kg injections of heroin within 10 daily sessions did not differ from vehicle-pretreated controls. In contrast, rats pre-exposed to THC subsequently self-administered significantly more heroin injections per session and showed significantly shorter post-injection pauses over a range of heroin doses (12.5-100 microg/kg/injection) using the variable-dose schedule. Interestingly, the maximum effort rats would exert to receive an injection of the different doses of heroin under the progressive-ratio schedule was not altered by THC pre-exposure. In a second group of rats, we varied the 'price' of heroin (responses required/dose), by manipulating FR response requirements at different doses of heroin across sessions, to calculate demand and response output curves. Again, consumption was significantly higher in the THC-treated rats at the lowest prices of heroin (FR1/100 microg/kg and FR1/50 microg/kg) but there were no differences in the reinforcing efficacy of heroin between THC- and vehicle-pretreated rats. Altogether, these results demonstrate that pre-exposure to THC alters some pharmacological effects of heroin that determine frequency of heroin taking, but offer no support for the hypothesis that pre-exposure to THC alters heroin's efficacy as a reinforcer.

Analgesics, Non-Narcotic↗
PubMed2003

Cannabinoid modulation of the reinforcing and motivational properties of heroin and heroin-associated cues in rats.

RATIONALE: Recently, we provided evidence for a cannabinoid mechanism in relapse to cocaine seeking in rats. There is also increasing evidence for functional cross-talk between cannabinoid and opioid systems in several physiological processes. OBJECTIVES: This study was designed to evaluate whether the cannabinoid system plays a role in mediating the reinforcing and motivational effects of heroin and heroin-paired stimuli. METHODS: Male Wistar rats were trained to self-administer heroin (50 microg/kg per infusion) on fixed (FR5) or progressive ratio schedules of reinforcement in the presence of a discriminative and discrete heroin-associated cue. The selective cannabinoid CB1 antagonist SR141716A was given 30 min before the session to determine its effect on responding for heroin. Separate groups of rats were subjected to extinction training during which heroin-associated cues were absent and no heroin was delivered. During subsequent reinstatement tests, the effects of the cannabinoid agonist HU210 and the antagonist SR141716A on reinstatement of heroin seeking were evaluated. RESULTS: The cannabinoid antagonist dose-dependently reduced responding for heroin on the FR5 schedule and to a greater extent on the progressive ratio schedule. HU210 (20 microg/kg) reinstated heroin seeking behaviour following a 2-week extinction period, whereas SR141716A dose-dependently attenuated heroin seeking that was provoked by a priming injection of heroin (0.25 mg/kg) and heroin seeking that was triggered by re-exposure to heroin paired stimuli. CONCLUSIONS: The results show that the reinforcing and motivational effects of heroin and heroin-paired stimuli are mediated, at least in part, by activation of cannabinoid CB1 receptors. Therefore, the present study provides a rationale for the use of cannabinoid antagonists in the treatment of opiate addiction.

Animals↗
PubMed2004

Adolescent and young adult heroin and non heroin users: a quantitative and qualitative study of experiences in a therapeutic community.

Admissions to treatment for heroin abuse have increased in recent years among the adolescent and young adult population, yet few studies have described whether, and to what extent, young heroin users differ from their non heroin-using peers. This exploratory study presents quantitative and qualitative data obtained from lifetime heroin and non heroin-using adolescents and young adults in a long-term, step-down therapeutic community. Self-report data from the Global Appraisal of Individual Needs (GAIN) were obtained from 22 lifetime heroin and 33 non heroin users on admission to residential treatment and 12 months later. Ethnographic interviews (n = 27) were conducted with heroin users at all stages of treatment. Results indicate that lifetime heroin users had greater polysubstance use and lower self-efficacy scores (i.e., confidence to resist relapse) on admission to treatment than non heroin users, and though improved, heroin users' self-efficacy scores remained lower than those of non heroin users at the 12 month follow-up. Ethnographic data suggested that adolescents who had used heroin "hit bottom" before entering treatment and credited treatment with providing the opportunity to change their lives. The overall comparability of treatment outcomes between the heroin and non heroin using groups shows that adolescents and young adult heroin users can achieve similar outcomes in an age-appropriate therapeutic community treatment setting.

Adolescent↗
PubMed2000

Quality of heroin and heroin-related deaths from 1987 to 1995 in Vienna, Austria.

AIMS: To investigate the quality of heroin seized in Vienna between 1987 and 1995 and to examine whether there was a relationship between the quality of heroin and the rate of drug-related deaths. DESIGN: Reports of heroin seizure analysis and post-mortem reports of heroin-related deaths in Vienna from 1987 to 1995 were analysed. RESULTS: There were 386 seizures of heroin comprising a total weight of 25 640.12 g heroin. All the seizures were in the base form. All seizures also contained a diluent, mainly lactose. Additionally, in 95 seizures caffeine, in four seizures paracetamol and in three seizures metaqualon were detected. Of a total of 764 drug-related deaths 506 cases were classified as heroin-related deaths. In 336 cases other central nervous system-depressant drugs and/or alcohol could be detected in the blood in addition to morphine (polydrug heroin-related deaths). There was evidence of a trend towards greater polydrug involvement during the study period. The age of victims of polydrug heroin-related deaths remained unchanged over time while the age of victims of pure heroin-related deaths decreased significantly. The morphine concentration in the medulla oblongata in heroin-related deaths decreased significantly. Finally, there was no statistically significant relationship between the rate of heroin-related deaths per year and the diacetylmorphine concentration of heroin seizures in that year. CONCLUSION: The results did not substantiate the widely held belief that increases in heroin-related deaths could be explained by an increase in the quality of heroin.

Adolescent↗
PubMed1996

Relapse to heroin-seeking in rats under opioid maintenance: the effects of stress, heroin priming, and withdrawal.

It is widely believed that opioid withdrawal symptoms contribute to relapse to opioid use, but relapse is highly probable in experienced users even after prolonged abstinence and during opioid maintenance therapy. We have found using an animal model of relapse, the reinstatement procedure, that the two events that reliably reinstate heroin-seeking behavior are reexposure to heroin, and brief exposure to footshock stress. Contrary to expectation, opioid antagonist-induced withdrawal does not reinstate heroin-seeking. We now report on reinstatement of heroin-seeking in rats trained to self-administer heroin and subsequently exposed to a maintenance dose of heroin via minipump and allowed to self-administer saline. With the minipump in, naloxone-induced withdrawal did not reinstate drug-seeking, a priming injection on heroin was only mildly effective, and footshock was highly effective. Twenty-four hours after removal of the minipump (spontaneous withdrawal), animals reinitiated heroin-seeking and, subsequently, both heroin and footshock reinstated heroin-seeking. In summary, brief exposure to stress reinstated heroin-seeking in both heroin-maintained and withdrawn animals. The heroin prime reliably reinstated drug-seeking only in the absence of the minipump; opioid "withdrawal," as such, did not reinstate drug-seeking behavior. Naloxone given to heroin-maintained animals induced withdrawal symptoms, caused a mild depression in the levels of dopamine and its metabolites in the nucleus accumbens septi (NAS), but did not reinstate drug-seeking. Reinstatement of heroin-seeking during spontaneous withdrawal was not accompanied by reductions in basal dopamine and its metabolites in NAS.

Animals↗
PubMed2002

Basolateral amygdala inactivation abolishes conditioned stimulus- and heroin-induced reinstatement of extinguished heroin-seeking behavior in rats.

RATIONALE: Drug-paired stimuli elicit drug craving and relapse in addicts and drug-seeking behavior in rats. The functional integrity of the basolateral amygdala (BLA) is necessary for reinstatement of cocaine-seeking behavior elicited by cocaine-conditioned stimuli, but not by cocaine itself. It is unclear, however, whether the BLA plays a similar role in reinstatement of heroin-seeking behavior. OBJECTIVES: To this end, we examined the effects of tetrodotoxin (TTX)-induced inactivation of the BLA on conditioned and heroin-primed reinstatement of extinguished heroin-seeking behavior. METHODS: Rats were trained to press a lever for IV infusions of heroin (maintenance dose of 25 microg/infusion) paired with presentations of a light-tone stimulus complex during daily 3-h sessions. Responding was then allowed to extinguish prior to reinstatement testing. Reinstatement of extinguished heroin-seeking behavior (i.e. lever pressing in the absence of heroin reinforcement) was measured in the presence of response-contingent presentation of the heroin-paired stimulus complex alone and then following TTX (5 ng/0.5 microl per side) or vehicle infused into the BLA. In a separate group of rats, reinstatement was measured after saline injection (SC) and then following heroin priming (0.25 mg/kg, SC) with TTX or vehicle infused into the BLA. RESULTS: Both response contingent presentation of the stimulus complex and heroin priming significantly reinstated extinguished heroin-seeking behavior, and BLA inactivation abolished the ability of the heroin-paired stimuli and of heroin priming to reinstate responding. CONCLUSIONS: These findings suggests that the BLA is a critical component of the neural circuitry that mediates conditioned and heroin-induced reinstatement of heroin-seeking behavior. Furthermore, different neural substrates may mediate drug-primed relapse to cocaine versus heroin-seeking behavior.

Amygdala↗
PubMed1999

Heroin chasers and heroin injectors: differences observed in a community sample in London, UK.

"Chasing the dragon" has spread rapidly as a method of use of heroin in many countries over the last quarter of a century, and is now the most widely used method of heroin use worldwide. However, little examination has been made of the differences in characteristics and drug-taking patterns between heroin chasers and injectors. In this study, a comparison is made of the personal, social and drug-taking characteristics of heroin users in a community sample (i.e., not drawn from treatment services, contacted through a range of non-treatment access routes), according to whether the heroin user was currently a heroin chaser or injector, and according to whether or not they had ever injected. Data were examined on 400 heroin users contacted and interviewed in South London by privileged access interviewers using a structured interview schedule. Severity of dependence was measured using the Severity of Dependence Scale (SDS). Heroin chasing and injecting were almost equally prevalent among this community sample. Of the 400 heroin users, 178 (44.5%) identified "chasing the dragon" as their current route of heroin use, and 222 (55.5%) injecting. Heroin chasers were younger, though they had first used at an older age, had a larger proportion of non-using friends, and contained larger proportions of women and people of Afro-Caribbean origin. Injectors were using higher daily doses and were significantly more likely to be using on a daily basis. Those who had never injected were more likely to be women and to have friends who did not use drugs. Severity of Dependence (SDS) scores were greater amongst injectors, with scores for injectors almost all being above the informal clinical threshold of greater than 5; while one third of the chasers had SDS scores below this level. Heroin chasing had been a longstanding pattern of behavior for a large proportion of the study sample. Chasers were generally less deeply involved in a heroin-using culture and were less likely to be using heroin daily. Almost all low scores for severity of dependence were seen among the chasers, though a significant number of chasers had dependence scores at the most extreme. Heroin chasers display distinctly different personal and drug-taking characteristics and will need to be the subject of separate research studies and clinical programs.

Adolescent↗
PubMed2005

Matching of treatment-resistant heroin-dependent patients to medical prescription of heroin or oral methadone treatment: results from two randomized controlled trials.

AIMS: To investigate which baseline patient characteristics of treatment-resistant heroin addicts differentially predicted treatment response to medical heroin prescription compared to standard methadone maintenance treatment. DESIGN: Two open-label randomized controlled trials; pooled data. SETTING: Methadone maintenance programmes and heroin treatment centres in six cities in the Netherlands. PARTICIPANTS: Four hundred and thirty heroin addicts. INTERVENTION: Methadone plus injectable heroin or methadone plus inhalable heroin compared to methadone alone prescribed over 12 months: heroin maximum 1000 mg per day, methadone maximum 150 mg per day. MAIN OUTCOME MEASURE: Dichotomous, multi-domain response index, including validated indicators of physical health, mental status and social functioning. FINDINGS: Data of the inhalable and injectable heroin trials were pooled. Intention-to-treat analysis showed that treatment with medically prescribed heroin plus methadone was significantly more effective (51.8% response) than standard methadone maintenance treatment (28.7%) (95% CI of response difference: 14.1-32.2%). Multivariate logistic regression analyses showed that only one of all baseline characteristics was predictive of a differential treatment effect: patients who had previously participated in abstinence-orientated treatment responded significantly better to heroin-assisted treatment than to methadone treatment (61% versus 24%), while patients without experience in abstinence-orientated treatment did equally well in heroin-assisted or methadone maintenance treatment (39% and 38%, respectively). CONCLUSIONS: The effect of heroin-assisted treatment is not dependent on clinical characteristics, with the exception of previous abstinence-orientated treatment: medical prescription of heroin is most effective for those patients who have previously participated in abstinence-orientated treatment.

Administration, Inhalation↗
PubMed2006

Choice between heroin and food in nondependent and heroin-dependent rhesus monkeys: effects of naloxone, buprenorphine, and methadone.

Several medications are approved for treatment of opiate abuse, but determinants of their clinical effectiveness are not completely understood. States of opiate dependence or withdrawal may constitute one important set of determinants. To test this hypothesis, the effects of naloxone, buprenorphine, and methadone were assessed on choice between heroin and food in nondependent rhesus monkeys and in heroin-dependent monkeys undergoing withdrawal. A choice procedure was used to permit dissociation of medication effects on the relative reinforcing properties of heroin from nonselective effects on response rates. In nondependent monkeys, increasing unit doses of heroin (0-0.1 mg/kg/injection) maintained dose-dependent increases in heroin choice. Chronic 5-day treatment with naloxone (0.01-0.32 mg/kg/h) or buprenorphine (0.01-0.1 mg/kg/day) produced dose-dependent rightward shifts in heroin choice dose-effect curves, whereas chronic methadone (0.1-0.56 mg/kg/h) had little effect on heroin choice up to doses that suppressed responding. In heroin-dependent monkeys, opiate withdrawal produced overt abstinence signs as well as increases in heroin choice, manifested as leftward shifts in heroin choice dose-effect curves. The withdrawal-associated increases in heroin choice suggest that opiate withdrawal increased the relative reinforcing efficacy of heroin in comparison with food, an effect that may be related to relapse in humans. Methadone prevented withdrawal-associated increases in heroin choice, whereas buprenorphine was less effective. These findings suggest that agonist medications such as methadone may derive their clinical utility from their ability to attenuate withdrawal-associated increases in opiate reinforcement. Moreover, this procedure may be useful for exploring mechanisms underlying withdrawal-associated increases in opiate reinforcement and for testing candidate medications.

Animals↗