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Objective To determine the cost utility of medical co-prescription of heroin compared with methadone maintenance treatment for chronic, treatment resistant heroin addicts.

Design Cost utility analysis of two pooled open label randomised controlled trials.

Setting Methadone maintenance programmes in six cities in the Netherlands.

Participants 430 heroin addicts.

Interventions Inhalable or injectable heroin prescribed over 12 months. Methadone (maximum 150 mg a day) plus heroin (maximum 1000 mg a day) compared with methadone alone (maximum 150 mg a day). Psychosocial treatment was offered throughout.

Main outcome measures One year costs estimated from a societal perspective. Quality adjusted life years (QALYs) based on responses to the EuroQol EQ-5D at baseline and during the treatment period.

Results Co-prescription of heroin was associated with 0.058 more QALYs per patient per year (95% confidence interval 0.016 to 0.099) and a mean saving of €12 793 (£8793, $16 122) (€1083 to €25 229) per patient per year. The higher programme costs (€16 222; lower 95% confidence limit €15 084) were compensated for by lower costs of law enforcement (- €4129; upper 95% confidence limit - €486) and damage to victims of crime (- €25 374; upper 95% confidence limit - €16 625). The results were robust for the use of national EQ-5D tariffs and for the exclusion of the initial implementation costs of heroin treatment. Completion of treatment is essential; having participated in any abstinence treatment in the past is not.

Conclusions Co-prescription of heroin is cost effective compared with treatment with methadone alone for chronic, treatment resistant heroin addicts.

Objective To determine whether supervised medical prescription of heroin can successfully treat addicts who do not sufficiently benefit from methadone maintenance treatment.

Design Two open label randomised controlled trials.

Setting Methadone maintenance programmes in six cities in the Netherlands.

Participants 549 heroin addicts.

Interventions Inhalable heroin (n = 375) or injectable heroin (n = 174) prescribed over 12 months. Heroin (maximum 1000 mg per day) plus methadone (maximum 150 mg per day) compared with methadone alone (maximum 150 mg per day). Psychosocial treatment was offered throughout.

Main outcome measures Dichotomous, multidomain response index, including validated indicators of physical health, mental status, and social functioning.

Results Adherence was excellent with 12 month outcome data available for 94% of the randomised participants. With intention to treat analysis, 12 month treatment with heroin plus methadone was significantly more effective than treatment with methadone alone in the trial of inhalable heroin (response rate 49.7% v 26.9%; difference 22.8%, 95% confidence interval 11.0% to 34.6%) and in the trial of injectable heroin (55.5% v 31.2%; difference 24.3%, 9.6% to 39.0%). Discontinuation of the coprescribed heroin resulted in a rapid deterioration in 82% (94/115) of those who responded to the coprescribed heroin. The incidence of serious adverse events was similar across treatment conditions.

Conclusions Supervised coprescription of heroin is feasible, more effective, and probably as safe as methadone alone in reducing the many physical, mental, and social problems of treatment resistant heroin addicts.

Most treatment studies of opioid-dependent populations have focused predominantly on heroin users, despite a recent increase in those dependent upon prescription opioids. A key methodological challenge involved in studying the latter group involves defining the population. Specifically, researchers must decide whether to include 1) concurrent heroin users and 2) individuals with pain. The multi-site Prescription Opioid Addiction Treatment Study is examining treatments for this population. This paper describes various inclusion criteria considered by the study team related to heroin use and pain. The goal was to recruit a distinct but generalizable population of individuals dependent upon prescription opioids.

Heroin addiction is a wide-reaching problem with a spectrum of damaging social consequences. Currently approved heroin addiction medications include drugs that bind at the same receptors (e.g. opioid receptors) occupied by heroin and/or its metabolites in the brain, but undesired side effects of these treatments, maintenance dependence and relapse to drug taking remains problematic. A vaccine capable of blocking heroin’s effects could provide an economical, long-lasting and sustainable adjunct to heroin addiction therapy without the side effects associated with available treatment options. Heroin, however, presents a particularly challenging vaccine target as it is metabolized to multiple psychoactive molecules of differing lipophilicity, with differing abilities to cross the blood brain barrier. In this review, we discuss the opiate scaffolding and hapten design considerations to confer immunogenicity as well as the specificity of the immune response towards structurally similar opiates. In addition, we detail different strategies employed in the design of immunoconjugates for a vaccine-based therapy for heroin addiction treatment.

Research on the neurocognitive characteristics of heroin addiction is sparse and studies that do exist include polydrug abusers; thus, they are unable to distinguish neurocognitive effects of heroin from those of other drugs. To identify neurocognitive correlates specific to heroin addiction, the present study was conducted in St. Petersburg, Russia where individuals typically abuse and/or become addicted to only one substance, generally alcohol or heroin. Heroin addicts were recruited from an inpatient treatment facility in St. Petersburg. Three comparison groups included alcoholics, addicts who used both alcohol and heroin, and non-abusers. Psychiatric, background, and drug history evaluations were administered after detoxification to screen for exclusion criteria and characterize the sample. Executive Cognitive Functions (ECF) that largely activate areas of the prefrontal cortex and its circuitry measured include complex visual pattern recognition (Paired Associates Learning), working memory (Delayed Matching to Sample), problem solving (Stockings of Cambridge), executive decision making (Cambridge Decision Making Task), cognitive flexibility (Stroop Color-Word Task) and response shifting (Stop Change Task). In many respects, the heroin addicts were similar to alcohol and alcohol\heroin dependent groups in neurocognitive deficits relative to controls. The primary finding was that heroin addicts exhibited significantly more disadvantageous decision making and longer deliberation times while making risky decisions than the other groups. Because the nature and degree of recovery from drug abuse are likely a function of the type or pattern of neurocognitive impairment, differential drug effects must be considered.

This article discusses various ethical and philosophical aspects of heroin addiction. It arose as a result of the plan by the Amsterdam city council to supply free heroin to drug addicts. The objective of treatment of heroin addicts is ambivalent because what is in fact a socio-cultural problem is transformed into a medical problem. The characteristics of this treatment are made explicit through a philosophical analysis which sees the medical intervention as part of a strategy aimed at achieving social normalisation. The reason why such a social control function is practised by physicians is discussed, as well as the reason why heroin users in particular are the object of such a process. In this paper, heroin addiction is considered primarily as a cultural problem. The consequences of this for treatment and ethics form the conclusion.

Background

Previous studies show that the acute administration of N-acetylcysteine inhibits the desire for cocaine in addicts and cocaine seeking in animals

Methods

Rats were trained to self-administer heroin and the reinstatement model of drug seeking was used to determine if chronic N-acetylcysteine treatment inhibited heroin seeking.

Results

Daily N-acetylcysteine administration inhibited cue- and heroin-induced seeking. Moreover, repeated N-acetylcysteine administration during extinction training reduced extinction responding and inhibited cue- and heroin-induced reinstatement for up to 40 days after discontinuing daily N-acetylcysteine injection.

Conclusions

These data show that daily N-acetylcysteine inhibits heroin-induced reinstatement and produces an enduring reduction in cue- and heroin-induced drug seeking for over a month after the last injection of N-acetylcysteine. Both the inhibitory effect of N-acetylcysteine on the reinstatement of heroin-seeking and the ability of N-acetylcysteine to reduce extinction responding support clinical evaluation of repeated N-acetylcysteine administration to decreases in drug seeking in heroin addicts.

Semisynthetic penicillinase-resistant penicillins are recommended for therapy of Staphylococcus aureus endocarditis, but evaluation of the efficacy and safety of individual agents has received little attention. At The New York Hospital, 11 heroin addicts and 5 nonaddicts were treated with nafcillin. The 11 addicts did well clinically, but four of the five nonaddicts had severe complications, and three of them died. Important adverse reactions to nafcillin occurred in two patients: one developed leukopenia, and one developed an extensive rash. Methicillin was employed to treat two heroin addicts and four nonaddicts. Five of the six patients were cured bacteriologically, but three patients developed nephritis and one patient developed an extensive rash. Nafcillin appears to be highly efficacious for the treatment of S. aureus endocarditis, yielding results at least equal to those obtained with other drugs. Because adverse reactions appear to occur more frequently with methicillin than with nafcillin, we regard nafcillin as the preferable penicillinase-resistant penicillin for the treatment of S. aureus endocarditis.

The μ-opioid receptor is the site of action of opiates and opioids. We examined whether there are differences in CpG dinucleotide methylation in the OPRM1 promoter between former heroin addicts and controls. We analyzed methylation at sixteen CpG dinucleotides in DNA obtained from lymphocytes of 194 Caucasian former severe heroin addicts stabilized in methadone maintenance treatment and 136 Caucasian control subjects. Direct sequencing of bisulfite-treated DNA showed that the percent methylation at two CpG sites was significantly associated with heroin addiction. The level of methylation at the −18 CpG site was 25.4% in the stabilized methadone maintained former heroin addicts and 21.4% in controls (p = 0.0035, generalized estimating equations (GEE); p = 0.0077, t-test; False Discovery Rate (FDR) = 0.048), and the level of methylation at the +84 CpG dinucleotide site was 7.4% in cases and 5.6% in controls (p = 0.0095, GEE; p = 0.0067, t-test; FDR = 0.080). Both the −18 and the +84 CpG sites are located in potential Sp1 transcription factor-binding sites. Methylation of these CpG sites may lead to reduced OPRM1 expression in the lymphocytes of these former heroin addicts.

Heroin addiction is a chronic complex disease with a substantial genetic contribution. This study was designed to identify gene variants associated with heroin addiction in African Americans. The emphasis was on genes involved in reward modulation, behavioral control, cognitive function, signal transduction, and stress response. We have performed a case-control association analysis by screening with 1350 variants of 130 genes. The sample consisted of 202 former severe heroin addicts in methadone treatment and 167 healthy controls with no history of drug abuse. Single-SNP, haplotype and multi-SNP genotype pattern analyses were performed. Seventeen SNPs showed point-wise significant association with heroin addiction (nominal P < 0.01). These SNPs are from genes encoding several receptors: adrenergic (ADRA1A), arginine vasopressin (AVPR1A), cholinergic (CHRM2), dopamine (DRD1), GABA-A (GABRB3), glutamate (GRIN2A), and serotonin (HTR3A), as well as alcohol dehydrogenase (ADH7), glutamic acid decarboxylase (GAD1 and GAD2), the nucleoside transporter (SLC29A1), and diazepam binding inhibitor (DBI). The most significant result of the analyses was obtained for the GRIN2A haplotype G-A-T (rs4587976-rs1071502-rs1366076) with protective effect (P uncorrected = 9.6E-05, P corrected = 0.058). This study corroborates several reported associations with alcohol and drug addiction as well as other related disorders, and extends the list of variants that may affect the development of heroin addiction. Further studies will be necessary to replicate these associations and to elucidate the roles of these variants in drug addiction vulnerability.

Objective: To evaluate an experimental heroin maintenance programme.

Design: Randomised trial.

Setting: Outpatient clinic in Geneva, Switzerland.

Subjects: Heroin addicts recruited from the community who were socially marginalised and in poor health and had failed in at least two previous drug treatments.

Intervention: Patients in the experimental programme (n=27) received intravenous heroin and other health and psychosocial services. Control patients (n=24) received any other conventional drug treatment (usually methadone maintenance).

Main outcome measures: Self reported drug use, health status (SF-36), and social functioning.

Results: 25 experimental patients completed 6 months in the programme, receiving a median of 480 mg of heroin daily. One experimental subject and 10 control subjects still used street heroin daily at follow up (difference 44%; 95% confidence interval 16% to 71%). Health status scores that improved significantly more in experimental subjects were mental health (0.58 SD; 0.07 to 1.10), role limitations due to emotional problems (0.95 SD; 0.11 to 1.79), and social functioning (0.65 SD; 0.03 to 1.26). Experimental subjects also significantly reduced their illegal income and drug expenses and committed fewer drug and property related offences. There were no benefits in terms of work, housing situation, somatic health status, and use of other drugs. Unexpectedly, only nine (38%) control subjects entered the heroin maintenance programme at follow up.

Conclusions: A heroin maintenance programme is a feasible and clinically effective treatment for heroin users who fail in conventional drug treatment programmes. Even in this population, however, another attempt at methadone maintenance may be successful and help the patient to stop using injectable opioids.

Key messages A heroin maintenance programme may be a useful treatment option for patients who do not succeed in conventional drug treatment programmes Patients randomly allocated to the Geneva heroin maintenance programme fared better that patients in conventional drug treatments in terms of street drug use, mental health, social functioning, and illegal activities Results of the trial apply only to a subgroup of severely addicted people who failed repeatedly in conventional drug treatments This evaluation does not distinguish between the effects of heroin itself and the effects of other medical and psychosocial services that were provided as part of the programme There was less demand for the heroin maintenance programme than anticipated and most control subjects declined entry into the programme at the end of the study

Objectives

To examine patterns of onset and abuse/dependence episodes of prescription opioid (PO) and heroin use disorders in a national sample of adults, and to explore differences by gender and substance abuse treatment status.

Methods

Analyses of data from the 2001–2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093).

Results

Of all respondents, 5% (n = 1815) reported a history of nonmedical PO use (NMPOU) and 0.3% (n = 150) a history of heroin use. Abuse was more prevalent than dependence among NMPOUs (PO abuse, 29%; dependence, 7%) and heroin users (heroin abuse, 63%; dependence, 28%). Heroin users reported a short mean interval from first use to onset of abuse (1.5 years) or dependence (2.0 years), and a lengthy mean duration for the longest episode of abuse (66 months) or dependence (59 months); the corresponding mean estimates for PO abuse and dependence among NMPOUs were 2.6 and 2.9 years, respectively, and 31 and 49 months, respectively. The mean number of years from first use to remission from the most recent episode was 6.9 years for PO abuse and 8.1 years for dependence; the mean number of years from first heroin use to remission from the most recent episode was 8.5 years for heroin abuse and 9.7 years for dependence. Most individuals with PO or heroin use disorders were remitted from the most recent episode. Treated individuals, whether their problem was heroin or POs, tended to have a longer mean duration of an episode than untreated individuals.

Conclusion

Periodic remissions from opioid or heroin abuse or dependence episodes occur commonly but take a long time. Timely and effective use of treatment services are needed to mitigate the many adverse consequences from opioid/heroin abuse and dependence.

A decade of research in Switzerland, The Netherlands, Germany, and Spain now constitutes a massive body of work supporting the use of heroin treatment for the most difficult patients addicted to opiates. These trials concur on this method's safety and efficacy and are now serving as a prelude to the institution of heroin treatment in clinical practice throughout Europe.

While the different sampling and research protocols for heroin treatment in these studies were important to the academic claims about specific results and conclusions that could be drawn from each study, the overall outcomes were quite clear – and uniformly positive. They all find that the use of prescribed pharmaceutical heroin does exactly what it is intended to do: it reaches a treatment refractory group of addicts by engaging them in a positive healthcare relationship with a physician, it reduces their criminal activity, improves their health status, and increases their social tenure through more stable housing, employment, and contact with family.

The Canadian trial (NAOMI), now underway for over a year, but not yet completed, now faces a dilemma about what to do with its patients who have successfully completed 12 months of heroin and must be withdrawn from heroin and transferred to other treatments in accordance with the research protocol approved by Government of Canada, federal granting body and host institutions. The problem is that the principal criterion for acceptance to NAOMI was their history of repeated failure in these very same treatment programs to which they will now be referred.

The existence of the results from abroad (some of which were not yet available when NAOMI was designed and initiated) now raises a very important question for Canada: is it ethical to continue to prohibit the medical use of heroin treatment that has already been shown to be feasible and effective in numerous medical studies throughout the world? And while this is being worked out, is it acceptable to require patients who have been successfully treated with heroin in Canada, to be forced to move back to less effective treatments (treatments that failed to be efficacious in the past)?

This essay discusses this dilemma and places it in the broader context of ethics, science, and health policy. It makes the case for continuation of the current successful patients in heroin treatment and the institution of heroin treatment to all Canadian patients living with active addictions who qualify.

In a group of 1066 heroin addicts, who were seeking treatment for opioid agonist treatment, we looked for differences in historical, demographic, and clinical characteristics, between patients with different levels of awareness of illness (insight). The results showed that, in the cohort studied, a majority of subjects lacked insight into their heroin-use behavior. Compared with the impaired-insight group, those who possessed insight into their illness showed significantly greater awareness of past social, somatic, and psychopathological impairments, and had a greater number of past treatment-seeking events for heroin addiction. In contrast with other psychiatric illnesses, the presence of awareness appears to be related to the passing of time and to the worsening of the illness. Methodologies to improve the insight of patients should, therefore, be targeted more directly on patients early in their history of heroin dependence, because the risk of lack of insight is greatest during this period.

Objective

An accumulating body of research suggests that former heroin abusers in methadone maintenance therapy (MMT) exhibit deficits in cognitive function. Whether these deficits are present in former methadone maintained patients following discontinuation of MMT is unknown. This study tests the hypothesis that former heroin users who have detoxified from methadone maintenance therapy and are drug-free have less pronounced cognitive impairment than patients continuing long-term MMT.

Method

A series of neuropsychological tests were administered to three groups of subjects: 29 former heroin addicts receiving methadone maintenance treatment, 27 former heroin addicts withdrawn from all opiates, and 29 healthy controls without a history of drug dependence. Testing included Wechsler Adult Intelligence Scale-Revised Vocabulary Test, the Stroop Color-Word Test, the Controlled Oral Word Association Test, the Benton Visual Retention Test, and a Substance Use Inventory.

Findings

Both methadone-maintained and abstinent subject groups performed worse than controls on tasks that measured verbal function, visual-spatial analysis and memory, and resistance to distractibility. Abstinent subjects performed worse than their methadone maintained counterparts on tests measuring visual memory and construct formation. Cognitive impairment did not correlate with any index of drug use.

Conclusions

We confirmed previous findings of neuropsychological impairment in long-term MMT recipients. Both patients receiving MMT and former heroin users in prolonged abstinence exhibited a similar degree of cognitive impairment. Cognitive dysfunction in patients receiving methadone maintenance may not resolve following methadone detoxification.

The National Institute on Drug Abuse Clinical Trials Network launched the Prescription Opioid Addiction Treatment Study (POATS) in response to rising rates of prescription opioid dependence and gaps in understanding the optimal course of treatment for this population. POATS employed a multi-site, two-phase adaptive, sequential treatment design to approximate clinical practice. The study took place at 10 community treatment programs around the United States. Participants included men and women age ≥18 who met Diagnostic and Statistical Manual, 4th Edition criteria for dependence upon prescription opioids, with physiologic features; those with a prominent history of heroin use (according to pre-specified criteria) were excluded. All participants received buprenorphine/naloxone (bup/nx). Phase 1 consisted of 4 weeks of bup/nx treatment, including a 14-day dose taper, with 8 weeks of follow-up. Phase 1 participants were monitored for treatment response during these 12 weeks. Those who relapsed to opioid use, as defined by pre-specified criteria, were invited to enter Phase 2; Phase 2 consisted of 12 weeks of bup/nx stabilization treatment, followed by a 4-week taper and 8 weeks of post-treatment follow-up. Participants were randomized at the beginning of Phase 1 to receive bup/nx, paired with either Standard Medical Management (SMM) or Enhanced Medical Management (EMM; defined as SMM plus individual drug counseling). Eligible participants entering Phase 2 were re-randomized to either EMM or SMM. POATS was developed to determine what benefit, if any, EMM offers over SMM in short-term and longer-term treatment paradigm. This paper describes the rationale and design of the study.

Background

Mental symptoms are common in heroin addiction and may arise from issues of addiction and withdrawal, raising doubts about the patients truly having co-morbid psychiatric diagnoses.

Methods

We studied the mental status of 1090 heroin addicts (831 males and 259 females aged between 16 and 51 years) at the beginning of treatment, and its relationship to relevant demographic and clinical data through the use of standardised instruments.

Results

A total of 506 (46.42%) heroin addicts showed depressive-anxious symptomatology, 421 (38.62%) had psychomotor excitement and 163 (14.95%) demonstrated a psychotic state. Patients with depressive-anxious symptomatology on the whole had a less severe addictive illness compared to those demonstrating excited and psychotic symptoms. The presence of depressive-anxious features was felt to not necessarily be indicative of the presence of a dual diagnosis.

Conclusion

The presence of depressive-anxious symptomatology in the clinical presentation in heroin addicts appears to be unrelated to 'dual diagnosis'.

Background

Addiction is a relapsing chronic condition in which psychiatric phenomena play a crucial role. Psychopathological symptoms in patients with heroin addiction are generally considered to be part of the drug addict's personality, or else to be related to the presence of psychiatric comorbidity, raising doubts about whether patients with long-term abuse of opioids actually possess specific psychopathological dimensions.

Methods

Using the Self-Report Symptom Inventory (SCL-90), we studied the psychopathological dimensions of 1,055 patients with heroin addiction (884 males and 171 females) aged between 16 and 59 years at the beginning of treatment, and their relationship to age, sex and duration of dependence.

Results

A total of 150 (14.2%) patients with heroin addiction showed depressive symptomatology characterised by feelings of worthlessness and being trapped or caught; 257 (24.4%) had somatisation symptoms, 205 (19.4%) interpersonal sensitivity and psychotic symptoms, 235 (22.3%) panic symptomatology, 208 (19.7%) violence and self-aggression. These dimensions were not correlated with sex or duration of dependence. Younger patients with heroin addiction were characterised by higher scores for violence-suicide, sensitivity and panic anxiety symptomatology. Older patients with heroin addiction showed higher scores for somatisation and worthlessness-being trapped symptomatology.

Conclusions

This study supports the hypothesis that mood, anxiety and impulse-control dysregulation are the core of the clinical phenomenology of addiction and should be incorporated into its nosology.

BACKGROUND

Prescription opioid dependence is increasing, but treatment outcomes with office-based buprenorphine/naloxone among these patients have not been described.

METHODS

We compared demographic, clinical characteristics and treatment outcomes among 200 patients evaluated for entry into a trial of primary care office-based buprenorphine/naloxone treatment stratifying on those who reported exclusive heroin use (n = 124), heroin and prescription opioid use (n = 47), or only prescription opioid use (n = 29).

RESULTS

Compared to heroin-only patients, prescription-opioid-only patients were younger, had fewer years of opioid use, and less drug treatment history. They were also more likely to be white, earned more income, and were less likely to have Hepatitis C antibodies. Prescription-opioid-only patients were more likely to complete treatment (59% vs. 30%), remained in treatment longer (21.0 vs. 14.2 weeks), and had a higher percent of opioid-negative urine samples than heroin only patients (56.3% vs. 39.8%), all p values < .05. Patients who used both heroin and prescription opioids had outcomes that were intermediate between heroin-only and prescription-opioid-only patients.

CONCLUSIONS

Individuals dependent on prescription opioids have an improved treatment response to buprenorphine/naloxone maintenance in an office-based setting compared to those who exclusively or episodically use heroin.

BACKGROUND

Prescription opioid dependence is increasing, but treatment outcomes with office-based buprenorphine/naloxone among these patients have not been described.

METHODS

We compared demographic, clinical characteristics and treatment outcomes among 200 patients evaluated for entry into a trial of primary care office-based buprenorphine/naloxone treatment stratifying on those who reported exclusive heroin use (n = 124), heroin and prescription opioid use (n = 47), or only prescription opioid use (n = 29).

RESULTS

Compared to heroin-only patients, prescription-opioid-only patients were younger, had fewer years of opioid use, and less drug treatment history. They were also more likely to be white, earned more income, and were less likely to have Hepatitis C antibodies. Prescription-opioid-only patients were more likely to complete treatment (59% vs. 30%), remained in treatment longer (21.0 vs. 14.2 weeks), and had a higher percent of opioid-negative urine samples than heroin only patients (56.3% vs. 39.8%), all p values < .05. Patients who used both heroin and prescription opioids had outcomes that were intermediate between heroin-only and prescription-opioid-only patients.

CONCLUSIONS

Individuals dependent on prescription opioids have an improved treatment response to buprenorphine/naloxone maintenance in an office-based setting compared to those who exclusively or episodically use heroin.

Successful treatment of drug addiction is hampered by high relapse rates during periods of abstinence. Neuroadaptation in the medial prefrontal cortex (mPFC) is thought to have a crucial role in vulnerability to relapse to drug seeking, but the molecular and cellular mechanisms remain largely unknown. To identify protein changes that contribute to relapse susceptibility, we investigated synaptic membrane fractions from the mPFC of rats that underwent 21 days of forced abstinence following heroin self-administration. Quantitative proteomics revealed that long-term abstinence from heroin self-administration was associated with reduced levels of extracellular matrix (ECM) proteins. After extinction of heroin self-administration, downregulation of ECM proteins was also present in the mPFC, as well as nucleus accumbens (NAc), and these adaptations were partially restored following cue-induced reinstatement of heroin seeking. In the mPFC, these ECM proteins are condensed in the perineuronal nets that exclusively surround GABAergic interneurons, indicating that ECM adaptation might alter the activity of GABAergic interneurons. In support of this, we observed an increase in the inhibitory GABAergic synaptic inputs received by the mPFC pyramidal cells after the re-exposure to heroin-conditioned cues. Recovering levels of ECM constituents by metalloproteinase inhibitor treatment (FN-439; i.c.v.) prior to a reinstatement test attenuated subsequent heroin seeking, suggesting that the reduced synaptic ECM levels during heroin abstinence enhanced sensitivity to respond to heroin-conditioned cues. We provide evidence for a novel neuroadaptive mechanism, in which heroin self-administration-induced adaptation of the ECM increased relapse vulnerability, potentially by augmenting the responsivity of mPFC GABAergic interneurons to heroin-associated stimuli.

Treatment research with opioid-dependent populations has not traditionally distinguished between those dependent on prescription opioids versus dependent upon heroin. Evidence suggests there is a substantial subpopulation of individuals with opioid dependence resulting largely or exclusively from prescription opioid use. Because this subpopulation may respond to treatment differently from heroin users, a method for discriminating DSM-IV opioid dependence due to prescription opioid use would provide more precision when examining this population. This paper describes an innovative method using a currently available diagnostic instrument, to diagnose DSM-IV opioid dependence and distinguish between dependence resulting from prescription opioids versus dependence upon heroin.

Background

In the United States, among those entering opioid treatment programs (OTPs), prescription opioid (PO) abusers tend to be younger than heroin users. Admissions of older persons to OTPs have been increasing, and it is important to understand typical patterns of use among those older enrolees.

Methods

To disentangle the effect of age on recent heroin and PO abuse 29,114 enrolees into 85 OTPs were surveyed across 34 states from 2005-2009. OTPs where PO use was prevalent were oversampled.

Results

Mean age was 34; 28% used heroin only. Younger enrolees had increased odds of using POs relative to using heroin only but mixed model analysis showed that much of the total variability in type of use was attributed to variation in age between OTPs rather than within OTPs.

Conclusions

Organizational and cultural phenomena (e.g., OTP characteristics) must be examined to better understand the context of individual characteristics (e.g., age). If nesting of enrolees within OTPs is ignored, then associations that primarily operate at the OTP level may be misinterpreted as exclusively dependent on individuals.

Medical treatment of heroin addiction with methadone and other pharmacotherapies has important benefits for individuals and society. However, regulatory policies have separated this treatment from the medical care system, limiting access to care and contributing to the social stigma of even effective addiction pharmacotherapy. Increasing problems caused by heroin addiction have added urgency to the search for policies and programs that improve the access to and quality of opiate addiction treatment. Recent initiatives aiming to reintegrate methadone maintenance and other addiction pharmacotherapies into medical practice may promote both expanded treatment capacity and increased physician expertise in addiction medicine. These initiatives include changes in federal oversight of the opiate addiction treatment system, the approval of physician office–based methadone maintenance programs for stabilized patients, and federal legislation that could enable physicians to treat opiate addiction with new medications in regular medical practice.

The historical patterns of opiate use show that sources and methods of access greatly influence who is at risk. Today, there is evidence that an enormous increase in the availability of prescription opiates is fuelling a rise in addiction nationally, drawing in new initiates to these drugs and changing the geography of opiate overdoses. Recent efforts at supply-based reductions in prescription opiates may reduce harm, but addicted individuals may switch to other opiates such as heroin. In this analysis, we test the hypothesis that changes in the rates of Prescription Opiate Overdoses (POD) are correlated with changes in the rate of heroin overdoses (HOD). ICD9 codes from the Nationwide Inpatient Sample and population data from the Census were used to estimate overall and demographic specific rates of POD and HOD hospital admissions between 1993 and 2009. Regression models were used to test for linear trends and lagged negative binomial regression models were used to model the interrelationship between POD and HOD hospital admissions. Findings show that whites, women, and middle-aged individuals had the largest increase in POD and HOD rates over the study period and that HOD rates have increased in since 2007. The lagged models show that increases in a hospitals POD predict an increase in the subsequent years HOD admissions by a factor of 1.26 (p<0.001) and that each increase in HOD admissions increase the subsequent years POD by a factor of 1.57 (p<0.001). Our hypothesis of fungibility between prescription opiates and heroin was supported by these analyses. These findings suggest that focusing on supply-based interventions may simply lead to a shift in use to heroin rather minimizing the reduction in harm. The alternative approach of using drug abuse prevention resources on treatment and demand-side reduction is likely to be more productive at reducing opiate abuse related harm.