DRD2 TaqIA polymorphism-related functional connectivity between anterior insula and dorsolateral prefrontal cortex predicts the retention time in heroin-dependent individuals under methadone maintenance treatment.

BACKGROUND: Dopamine receptor D2 (DRD2) TaqIA polymorphism has an influence on addiction treatment response and prognosis by mediating brain dopaminergic system efficacy. Insula is crucial for conscious urges to take drugs and maintain drug use. However, it remains unclear about the contribution of DRD2 TaqIA polymorphism to the regulation of insular on addiction behavioral and its relation with the therapeutic effect of methadone maintenance treatment (MMT). METHODS: 57 male former heroin dependents receiving stable MMT and 49 matched male healthy controls (HC) were enrolled. Salivary genotyping for DRD2 TaqA1 and A2 alleles, brain resting-state functional MRI scan and a 24-month follow-up for collecting illegal-drug-use information was conducted and followed by clustering of functional connectivity (FC) patterns of HC insula, insula subregion parcellation of MMT patients, comparing the whole brain FC maps between the A1 carriers and non-carriers and analyzing the correlation between the genotype-related FC of insula sub-regions with the retention time in MMT patients by Cox regression. RESULTS: Two insula subregions were identified: the anterior insula (AI) and the posterior insula (PI) subregion. The A1 carriers had a reduced FC between the left AI and the right dorsolateral prefrontal cortex (dlPFC) relative to no carriers. And this reduced FC was a poor prognostic factor for the retention time in MMT patients. CONCLUSION: DRD2 TaqIA polymorphism affects the retention time in heroin-dependent individuals under MMT by mediating the functional connectivity strength between left AI and right dlPFC, and the two brain regions are promising therapeutic targets for individualized treatment.

The Long-Term Relationship Between Cannabis and Heroin Use: An 18- to 20-year Follow-Up of the Australian Treatment Outcome Study (ATOS).

OBJECTIVE: Cannabis use is common among individuals with opioid use disorder, but it remains unclear whether cannabis use is associated with an increase or a reduction in illicit opioid use. To overcome limitations identified in previous longitudinal studies with limited follow-ups, the authors examined a within-person reciprocal relationship between cannabis and heroin use at several follow-ups over 18 to 20 years. METHODS: The Australian Treatment Outcome Study (ATOS) recruited 615 people with heroin dependence in 2001 and 2002 and reinterviewed them at 3, 12, 24, and 36 months as well as 11 and 18-20 years after baseline. Heroin and cannabis use were assessed at each time point using the Opiate Treatment Index. A random-intercept cross-lagged panel model analysis was conducted to identify within-person relationships between cannabis use and heroin use at subsequent follow-ups. RESULTS: After accounting for a range of demographic variables, other substance use, and mental and physical health measures, an increase in cannabis use 24 months after baseline was significantly associated with an increase in heroin use at 36 months (estimate=0.21, SE=0.10). Additionally, an increase in heroin use at 3 months and 24 months was significantly associated with a decrease in cannabis use at 12 months (estimate=-0.27, SE=0.09) and 36 months (estimate=-0.22, SE=0.08). All other cross-lagged associations were not significant. CONCLUSIONS: Although there was some evidence of a significant relationship between cannabis and heroin use at earlier follow-ups, this was sparse and inconsistent across time points. Overall, there was insufficient evidence to suggest a unidirectional or bidirectional relationship between the use of these substances.

Cognitive Enhancer Donepezil Attenuates Heroin-Seeking Behavior Induced by Cues in Rats.

PURPOSE: Opioid use disorder is a significant global problem. Chronic heroin use is associated with impairment of cognitive function and conscious control ability. The cholinergic system can be disrupted following heroin administration, indicating that activation of the cholinergic system may prevent chronic heroin misuse. Donepezil as an inhibitor of cholinesterase has been reported to clinically improve cognition and attention. In this study, the inhibition of heroin self-administration and heroin-seeking behaviours by donepezil were evaluated in rats. METHODS: Rats were trained to self-administer heroin every four hours for 14 consecutive days under a fixed ratio 1 (FR1) reinforcement schedule, then underwent withdrawal for two weeks. A progressive ratio schedule was then used to evaluate the relative motivational value of heroin reinforcement. After withdrawal, a conditioned cue was introduced for the reinstatement of heroin-seeking behaviour. Donepezil (0.3-3 mg/kg, i.p.) was used during both the FR1 heroin self-administration and progressive ratio schedules. Immunohistochemistry was used to investigate the mechanism of action of donepezil in the rat brain. RESULTS: Pre-treatment with high dose donepezil (3 mg/kg) but not low doses (0.3-1 mg/kg) significantly inhibited heroin self-administration under the FR1 schedule. Donepezil decreased motivation values under the progressive ratio schedule in a dose-dependent manner. All doses of donepezil (1-3 mg/kg) decreased the reinstatement of heroin seeking induced by cues. Correlation analysis indicated that the inhibition of donepezil on heroin-seeking behaviour was positively correlated with an increased expression of dopamine receptor 1 (D1R) and dopamine receptor 2 (D2R) in the nucleus accumbens (NAc) and increased expression of choline acetyltransferase (ChAT) in the ventral tegmental area (VTA). CONCLUSIONS: The present study demonstrated that donepezil could inhibit heroin intake and heroin-seeking behaviour. Further, donepezil could regulate dopamine receptors in the NAc via an increase of acetylcholine. These results suggested that donepezil could be developed as a potential approach for the treatment of heroin misuse.

'This is hardcore': a qualitative study exploring service users' experiences of Heroin-Assisted Treatment (HAT) in Middlesbrough, England.

BACKGROUND: Heroin-Assisted Treatment (HAT) is well evidenced internationally to improve health and social outcomes for people dependent on opioids who have not been helped by traditional treatment options. Despite this evidence base, England has been slow to implement HAT. The first service outside of a trial setting opened in 2019, providing twice-daily supervised injections of medical-grade heroin (diamorphine) to a select sample of high-risk heroin users in Middlesbrough. This paper explores their experiences, including the negotiation of the strict regularly controls required of a novel intervention in the UK context. METHODS: We conducted in-depth interviews with service providers and users of the Middlesbrough HAT service between September and November 2021. Data from each group were thematically analysed and reported separately. This paper details the experiences of the twelve heroin dependent men and women accessing HAT. RESULTS: Participants' accounts of HAT treatment evidenced a tension between the regulatory constraints and uncertainty of treatment provision, and the positive outcomes experienced through supportive service provision and an injectable treatment option. Limited confidence was held in treatment efficacy, longevity of funding, and personal capacity for treatment success. This was counteracted by a strong motivation to cease engagement with the illicit drug market. While attendance requirements placed restrictions on daily activities, participants also experienced benefits from strong, supportive bonds built with the service providers through their continued engagement. CONCLUSIONS: The Middlesbrough HAT programme provided benefits to a high-risk population of opioid dependent people who were unable or disinclined to participate in conventional opioid substitution treatments. The findings in this paper highlight the potential for service modifications to further enhance engagement. The closure of this programme in 2022 prohibits this opportunity for the Middlesbrough community, but holds potential to inform advocacy and innovation for future HAT interventions in England.

Heroin assisted treatment for key health outcomes in people with chronic heroin addictions: A context-focused systematic review.

BACKGROUND AND AIMS: Randomised controlled trials in Europe and Canada have shown that supervised heroin assisted treatment (HAT) is an effective treatment option for people with long-term heroin addictions for whom the standard opioid substitution treatments (OST) have not been effective. This review aims to evaluate the effectiveness of supervised HAT and analyse the significance of context and implementation in the design of successful HAT programmes. METHODS: PubMed, CENTRAL, Embase, and Web of Science were searched to identify randomised controlled trials (RCT) and systematic reviews evaluating supervised HAT compared to any other OST. Studies were eligible for inclusion if they were published in English, evaluated a supervised form of HAT, and included illegal drug use and/or health as a primary outcome measure. There were no restrictions on publication date. The following outcomes of the included studies were analysed using narrative synthesis and meta-analysis where possible: retention, street drug use, health, and social functioning. RESULTS: Nine randomised controlled trials spanning eight studies (n = 2331) and three systematic reviews met the inclusion criteria. Seven of the eight studies compared HAT to methadone maintenance treatment (MMT). One study compared HAT to injectable hydromorphone in a double-blind non-inferiority trial. Meta-analysis was performed on pooled results of retention across all included studies and found that HAT has a statistically significant effect on retention [Z = 7.65 (P > 0.0001)]. Five of the eight included studies found that supervised HAT reduces participants' use of illegal drugs more significantly than MMT. Evidence of improved health in participants receiving supervised HAT compared to other OSTs was inconsistent; positive effects were observed in three of the included studies (n = 1626). CONCLUSION: When compared to methadone maintenance treatment (MMT), heroin assisted treatment (HAT) more consistently retains people with heroin addictions in treatment and reduces their consumption of illicit drugs. TRIAL REGISTRATION: PROSPERO registration: CRD42022341306.

Changing Landscape of Fentanyl/Heroin Use and Distribution.

OBJECTIVE: To understand the geopolitics of the supply of fentanyl and heroin. RESULTS: In our practice, the percent of fentanyl positive drug tests increased from years 2016 to 2022, but heroin positive drug tests decreased by 80% in the same period. CONCLUSION: Fentanyl has replaced heroin as a street drug for opioid dependent drug users.

A method of diamorphine (heroin) administration for harm reduction.

As societal attitudes toward narcotics have changed, harm reduction strategies have emerged which make it safer to inject intravenous drugs. Diamorphine (heroin) is commonly sold as its free base-better known as brown-which has extremely poor aqueous solubility. As such, it needs to be chemically modified (cooked) to enable administration. Needle exchange programmes commonly supply citric or ascorbic acids which facilitate intravenous administration by increasing heroin solubility. If heroin users mistakenly add too much acid, the low solution pH can cause damage to their veins and, after repeated injury, could result in the loss of that injection site. Currently, advice cards supplied with these exchange kits suggest that the acid should be measured in pinches, which could result in considerable error. This work employs Henderson-Hasselbalch models to analyse the risk of venous damage by placing solution pH within the context of the buffer capacity of the blood. These models also highlight the significant risk of heroin supersaturation and precipitation within the vein, an event that has the potential to cause further harm to the user. This perspective closes with a modified administration method which could be included as part of a wider harm reduction package.

Relapse risk revealed by degree centrality and cluster analysis in heroin addicts undergoing methadone maintenance treatment.

BACKGROUND: Based on hubs of neural circuits associated with addiction and their degree centrality (DC), this study aimed to construct the addiction-related brain networks for patients diagnosed with heroin dependence undertaking stable methadone maintenance treatment (MMT) and further prospectively identify the ones at high risk for relapse with cluster analysis. METHODS: Sixty-two male MMT patients and 30 matched healthy controls (HC) underwent brain resting-state functional MRI data acquisition. The patients received 26-month follow-up for the monthly illegal-drug-use information. Ten addiction-related hubs were chosen to construct a user-defined network for the patients. Then the networks were discriminated with K-means-clustering-algorithm into different groups and followed by comparative analysis to the groups and HC. Regression analysis was used to investigate the brain regions significantly contributed to relapse. RESULTS: Sixty MMT patients were classified into two groups according to their brain-network patterns calculated by the best clustering-number-K. The two groups had no difference in the demographic, psychological indicators and clinical information except relapse rate and total heroin consumption. The group with high-relapse had a wider range of DC changes in the cortical-striatal-thalamic circuit relative to HC and a reduced DC in the mesocorticolimbic circuit relative to the low-relapse group. DC activity in NAc, vACC, hippocampus and amygdala were closely related with relapse. CONCLUSION: MMT patients can be identified and classified into two subgroups with significantly different relapse rates by defining distinct brain-network patterns even if we are blind to their relapse outcomes in advance. This may provide a new strategy to optimize MMT.

A 35-year follow-up study of patients admitted to methadone treatment between 1982-1984 in Asturias, Spain. / Estudio de seguimiento de 35 años de pacientes admitidos a tratamiento con metadona entre 1982-1984 en Asturias, España.

The objective was to evaluate outcomes in a heroin-dependent population 35 years after first enrolment in methadone maintenance treatment (MMT).  An ad hoc protocol was used to assess drug misuse, treatment, and drug-related morbidity in the survivor sample. The standardized mortality ratio (SMR) and 95% confidence interval (CI) were calculated.  A total of 214 heroin-dependent patients entered MMT between 1982 and 1984 in the Asturias Public Health Service. Information was received on 195 subjects, of whom 146 were deceased.  Men accounted for 77.5% of the study cohort. Over the 35-year follow-up period, the SMR was 11.75 (95% CI = 9.95 - 13.77). In the survivor sample, 5.7% were still enrolled in MMT; human immunodeficiency virus (HIV) was diagnosed in 38.77% and hepatitis B/C in 73.46%. No differences were found between sexes in mortality or HIV and hepatitis B/C status. None of the female survivors were using heroin at the 35-year follow-up compared with 5.26% of males. In conclusion, our study confirms the high long-term mortality rate of heroin addicts, even after enrollment in MMT.

El objetivo fue evaluar el estado de una población dependiente a la heroína 35 años después de su primera inscripción en un tratamiento de mantenimiento con metadona (TMM). Se utilizó un protocolo ad hoc para evaluar morbilidad, consumo y tratamiento de la adicción en la muestra de supervivientes. Se calculó la razón de mortalidad estandarizada (RME) con un intervalo de confianza (IC) del 95%. Un total de 214 pacientes ingresaron en TMM entre 1982 y 1984 en el Servicio de Salud Pública de Asturias. Se recibió información sobre 195 sujetos, de los cuales 146 habían fallecido. Los hombres representaron el 77,5% de la cohorte del estudio. Durante el período de seguimiento de 35 años, la RME fue de 11,75 (IC 95% = 9,95 ­ 13,77). En la muestra de supervivientes, el 5,7% todavía estaba inscrito en TMM; el virus de inmunodeficiencia humana (VIH) se diagnosticó en un 38,77% y la hepatitis B/C en un 73,46%; el consumo actual de heroína se informó en un 4,1%. No hubo diferencias de género en la mortalidad o la condición de VIH y hepatitis B/C. Ninguna de las mujeres consumía heroína en el seguimiento de 35 años en comparación con el 5,26% de los hombres. En conclusión, nuestro estudio confirma la alta tasa de mortalidad a largo plazo, incluso después de la inscripción en TMM.

The Cost-Effectiveness of Financial Incentives to Achieve Heroin Abstinence in Individuals With Heroin Use Disorder Starting New Treatment Episodes: A Cluster Randomized Trial-Based Economic Evaluation.

OBJECTIVES: Cost-effectiveness analysis of two 12-week contingency management (CM) schedules targeting heroin abstinence or attendance at weekly keyworker appointments for opioid agonist treatment compared with treatment as usual (TAU). METHODS: A cost-effectiveness analysis was conducted alongside a cluster randomized trial of 552 patients from 34 clusters (drug treatment clinics) randomly allocated 1:1:1 to opioid agonist treatment plus weekly keyworker appointments with (1) CM targeted at heroin abstinence (CM abstinence), (2) CM targeted at on-time attendance at weekly appointments (CM attendance), or (3) no CM (TAU). The primary cost-effectiveness analysis at 24 weeks after randomization took a societal cost perspective with effects measured in heroin-negative urine samples. RESULTS: At 24 weeks, mean differences in weekly heroin-negative urine results compared with TAU were 0.252 (95% confidence interval [CI] -0.397 to 0.901) for CM abstinence and 0.089 (95% CI -0.223 to 0.402) for CM attendance. Mean differences in costs were £2562 (95% CI £32-£5092) for CM abstinence and £317 (95% CI -£882 to £1518) for CM attendance. Incremental cost-effectiveness ratios were £10 167 per additional heroin-free urine for CM abstinence and £3562 for CM attendance with low probabilities of cost-effectiveness of 3.5% and 36%, respectively. Results were sensitive to timing of follow-up for CM attendance, which dominated TAU (better outcomes, lower costs) at 12 weeks, with an 88.4% probability of being cost-effective. Probability of cost-effectiveness remained low for CM abstinence (8.6%). CONCLUSIONS: Financial incentives targeted toward heroin abstinence and treatment attendance were not cost-effective over the 24-week follow-up. Nevertheless, CM attendance was cost-effective over the treatment period (12 weeks), when participants were receiving keyworker appointments and incentives.

[Substitution treatments for opiate-dependent users. An experience of the Integrated Addiction Treatment Center in Dakar]. / Traitement de substitution des usagers dépendants des opiacés - L'expérience du Centre de prise en charge intégré des addictions de Dakar.

Methadone and buprenorphine are the two maintenance treatments in opiate addicts authorised in France since the end of the 1990's. More recently, some African countries such as Senegal have implemented a new health policy focused on reducing the risks by encouraging the use of methadone as maintenance treatment. The objectives of maintenance therapy are to reduce morbidity and mortality related to the consumption of heroin and other street opioids, to promote the integration of drug users into the healthcare system, and more generally, to improve their social integration. However, this strategy might have limitations in practice. Here, we report the experience of the Integrated Addiction Treatment Center in Dakar, Senegal, and discuss ethical considerations at both the individual and collective levels, which may improve care of opiate-dependent users in practice, especially in Africa.

Title: Traitement de substitution des usagers dépendants des opiacés - L'expérience du Centre de prise en charge intégré des addictions de Dakar. Abstract: La méthadone et la buprénorphine sont les deux traitements de substitution des opiacés autorisés en France depuis la fin des années 1990. Plus récemment, certains pays africains, comme le Sénégal, ont mis en place une nouvelle politique de santé axée sur la réduction des risques, en encourageant le recours aux traitements de substitution des opiacés. Les objectifs de la substitution sont de réduire la morbi-mortalité liée à la consommation d'héroïne ou d'autres opioïdes de rue, de favoriser l'insertion des usagers de drogue dans le système de soins, et, plus généralement, de faciliter leur insertion sociale. Cette nouvelle stratégie trouve néanmoins des limites dans la pratique. Nous rapportons dans cette revue l'expérience du Centre de prise en charge intégré des addictions de Dakar, au Sénégal, et proposons une réflexion éthique, tant individuelle que collective, afin d'améliorer le traitement de substitution des opiacés, notamment en Afrique.

Nasal administration of diacetylmorphine improved the adherence in a patient receiving heroin-assisted treatment.

BACKGROUND: Traditional heroin-assisted treatment in Switzerland consists of oral and injectable diacetylmorphine (pharmaceutical heroin) administration. To date, no suitable treatment option is available for patients who crave rapid onset ("rush") but are either unable to inject or primarily sniff or inhale illicit heroin. We present a patient who successfully switched to intranasal heroin-assisted treatment following several unsuccessful treatment attempts. CASE PRESENTATION: A 29-year-old male with severe opioid use disorder, injection substance use, and concomitant cocaine use, previously prescribed slow-release oral morphine, was started on intravenous diacetylmorphine. Due to complications and harms associated with intravenous injections, nasal diacetylmorphine was prescribed. With this novel route of administration, the patient who had previously been unable to adhere to other OAT options remained in treatment. Health outcomes improved by reduction of injection-related harms, increased adherence to the heroin-assisted treatment regimen, and increased collaboration with the therapeutic staff. CONCLUSIONS: Nasal heroin-assisted treatment can be a feasible therapeutic option for individuals with severe opioid use disorder who crave the fast onset of effect of diacetylmorphine but are unable to inject intravenously.

"They say it's fentanyl, but they honestly look like Perc 30s": Initiation and use of counterfeit fentanyl pills.

BACKGROUND: Worsening of the overdose crisis in the USA has been linked to the continuing proliferation of non-pharmaceutical fentanyl (NPF). The recent wave of NPF spread in the USA has been fueled by an increased presence of counterfeit pills that contain NPF. This qualitative study aims to characterize the motivation and practices of counterfeit NPF pill initiation and use among individuals using illicit opioids in Arizona. METHODS: Between October 2020 and May 2021, semi-structured interviews were conducted with 22 individuals meeting the following eligibility criteria: (1) 18 years or older; (2) residence in Arizona; and (3) use of illicit opioids in the past 30 days and/or opioid use disorder treatment in the past 12 months. Participants were recruited through referrals by a harm reduction organization, craigslist ads, and referrals by other participants. Interviews were conducted virtually via Zoom. Qualitative interviews were transcribed and analyzed thematically using NVivo. RESULTS: Out of 22 participants, 64% were male, and 45% were ethnic minorities. Age ranged between 25 and 51 years old. Participants noted significant recent increases in the availability of counterfeit NPF pills ("blues," "dirty oxys") that were most commonly used by smoking. The majority indicated first trying NPF pills in the past year, and the first use often occurred in situations of reduced access to heroin or pharmaceutical opioids. Participant decisions to switch over to more frequent NPF pill use or to maintain some levels of heroin use were shaped by local drug availability trends and personal experiences with NPF effects. They were also influenced by conflicting views of social acceptability of pharmaceutical-like drugs, perceived harms of NPF in terms of overdose risks and increased difficulty of quitting, and perceived benefits of switching to the non-injection route of opioid administration (e.g., from injecting heroin to smoking NPF pills). CONCLUSION: Our findings highlight the need for the implementation of novel policy, treatment, and harm reduction approaches to address the growing unpredictability of drug supply and NPF pill-specific risks, attitudes, and behaviors.

Benefits of Intranasal Administration of Diamorphine and Midazolam in the Management of Patients Receiving Palliative Care in the Community: A Case Series.

Opioids and benzodiazepines are cornerstones of the pharmacological management of pain and agitation in palliative medicine. Oral drug delivery is the most popular route of administration, with the subcutaneous route typically utilized where oral medications are not tolerated or are ineffective. Intranasal drug delivery offers an important alternative administration route, with benefits including ease of administration, tolerability and avoidance of needle use, and is particularly useful in the community, where medications may be administered by lay carers or by patients themselves. Intranasal diamorphine and intranasal midazolam both have demonstrated efficacy and safety in adult and pediatric cohorts, however there is limited research into their use in managing pain and agitation in palliative care. We describe the management of three patients under the community palliative care team who received intranasal diamorphine, two of whom also received intranasal midazolam, to manage breakthrough symptoms of pain and agitation at home. In each case, the patient or their relative was taught how to prepare and administer the relevant intranasal medication. This case series demonstrates that for selected patients, diamorphine and midazolam administered intranasally by patients or lay carers at home is efficacious, acceptable and generally well tolerated.

Effect of substance use on premature mortality among severely hypertensive African Americans.

Low-income African Americans residing in impoverished neighborhoods confront myriad barriers to adhering to antihypertensive regimens. Substance use may thwart medication adherence and lifestyle modification efforts, which has implications for excess cardiovascular disease mortality. The Inner-City Hypertension and Body Organ Damage (ICHABOD) Study was a longitudinal cohort study that evaluated causes of mortality among African Americans who lived in urban areas, had severe, poorly controlled hypertension, and were admitted to a local hospital between 1999-2001 and 2002-2004. The authors employed Cox proportional hazards models to assess mortality associated with illicit substance use, including use of heroin and cocaine, as well as by use of tobacco and alcohol. Among192 participants with poorly controlled hypertension, 30% were active illicit substance users (specifically, 22.7% heroin users, 19.8% were cocaine users, and 30.7% were both cocaine and heroin users). The mean age among substance non-users was 52.3 years versus 48.7 years among those reporting current use. Mortality over 7.6 years of follow-up was 52.5% among substance users and 33.8% among nonusers (p-value, 0.01). After adjusting for potential confounders, the hazard ratio (HR) for cocaine use was 2.52 (95% confidence interval (CI) 1.38-4.59), while the HR for heroin use was 2.47 (95% CI 1.42-4.28) and the HR for both was 2.75 (95% CI 1.60-4.73). Substance use was associated with increased mortality among urban black Americans with poorly controlled hypertension. These data suggest the need for targeted interventions to support African Americans who have poorly controlled hypertension and use illicit substances, as a means of reducing excess mortality.

Frontal Lobe Functions, Demoralization, Depression and Craving as Prognostic Factors and Positive Outcomes of Patients with Heroin Use Disorder Receiving 6 Months of Methadone Maintenance Treatment.

Methadone maintenance therapy (MMT) is a well-established and effective treatment for heroin use disorders. Whether frontal lobe function and demoralization serve as suitable prognostic and outcome assessment factors remains unknown. A quasi-experimental study was conducted with a single-group repeated-measures design at a medical center and mental hospital in Taiwan. We enrolled 70 participants (39 completed treatments and 31 dropped out). Frontal lobe function, demoralization, depression, and craving at three time points were analyzed. There were differences between patients who completed the treatment (n = 39) and those who did not (n = 31). Thirty-nine patients completed the treatment (average age, 45.5 years; 89.7% men; average duration of heroin use, 27.21 years; MMT, 38.18 mg/day). Post-MMT (6 months), frontal lobe function, demoralization, depression, and craving significantly improved. Dropouts had higher frontal lobe function, lower demoralization, higher craving, younger age, and earlier onset age than patients who completed the pretest treatment. Clinicians should be aware of the severity of demoralization. Clinicians may select suitable patients for MMT by assessing frontal lobe function, demoralization, craving, age, and onset age. A 6-month course of MMT improved demoralization, frontal lobe function, depression, and addiction. Six months of treatment was more effective than 3 months. Suitable patient identification and continuous treatment are important in MMT.

Does heroin-assisted treatment reduce crime? A review of randomized-controlled trials.

BACKGROUND AND AIMS: Several randomized controlled trials (RCTs) conclude that heroin-assisted-treatment (HAT) has a larger benefit-cost ratio than oral methadone because HAT more reliably and substantially reduces participants' criminal activity. This review: (1) summarizes results from RCTs concerning the comparative effectiveness of HAT for reducing criminal activity and (2) examines the role of different mechanisms for explaining changes in crime. DESIGN: Systematic search of five databases for RCTs evaluating comparative effectiveness of HAT on participant crime outcomes and potential mediators of crime. Narrative synthesis with tabular comparisons of outcomes extracted across RCTs. SETTING: Europe and Canada. PARTICIPANTS: Twenty studies, spanning 10 RCTs with 2427 participants, met inclusion criteria. INTERVENTIONS: HAT compared to other treatments for opioid use disorder, primarily oral methadone. MEASUREMENTS: The primary outcome was criminal activity. Mediator outcomes included illicit heroin use, drug expenditures, employment and earnings and social functioning. FINDINGS: All trials found significantly reduced criminal activity among HAT participants, and four found significantly larger reductions for HAT compared to control condition [median odds ratios (ORs) = 0.45]. Reductions in crime are concentrated in drug-related and property offenses (ORs range from 0.14 to 0.90 and from 0.12 to 1.89, respectively). Comparative efficacy of HAT for reducing illicit heroin use probably explains reductions in drug possession offenses, but does not show consistent correlation with drug dealing or property offenses. While three trials showed reductions in drug expenditures as possibly driving crime reductions, others did not report expenditures. There is little evidence that treatment effects on economic and social functioning outcomes explain within-trial changes in criminal activity. CONCLUSIONS: Existing literature suggests that heroin-assisted treatment reduces criminal activity, but trials varied in whether these effects exceeded those from oral methadone treatment. Inconsistency in outcome measures across trials complicates understanding drivers of heterogeneity. More detailed information on legal and illegal income, drug expenditures and social interactions could improve our understanding of the causal mechanisms underlying the effect of heroin-assisted-treatment on crime.

«One prick and then it´s done¼: a mixed-methods exploratory study on intramuscular injection in heroin-assisted treatment.

BACKGROUND: Intramuscular (IM) injection of drugs is associated with high rates of injecting-related injuries and diseases. However, little is known about the role of this route of administration in heroin-assisted treatment. The aim of this study was to determine the prevalence of IM diacetylmorphine administration and associated complications as well as to explore patients' views and opinions on the topic and the underlying reasons for this practice. METHODS: The research site was a Swiss outpatient treatment centre specialised in heroin-assisted treatment. We conducted in-depth interviews with two patients who intramuscularly inject diacetylmorphine. Interviews were analysed qualitatively, and emerging themes were used to develop a 38-item questionnaire on IM injections. We then offered this questionnaire to all patients in the treatment centre. RESULTS: Five main themes emerged from the in-depth interviews: poor venous access, side effects, subjective effects, procedure for IM injection, and consideration of alternatives to IM. These themes covered the rationale for using this route of administration, complications, subjective effects of IM diacetylmorphine, hygiene and safety measures as well as alternative routes of administration. Fifty-three patients filled in the questionnaire. The lifetime prevalence of IM injections was 60.4% (n = 32) and 34.4% (n = 11) of the patients stated that IM injection was their primary route of administration. No participant reported using the IM route for street drugs. The main reason for IM injections was poor vein access. Other reasons given were time saving and less risk of injuries. Complications included induration of muscle tissue and pain, whereas more severe complications like thrombosis and infections of the injection site were reported much less often. CONCLUSION: As the population of opioid-dependent individuals is aging and the deterioration of access veins is likely to increase, the frequency of IM injecting will equally increase. Even though our data show that the IM injection of diacetylmorphine in a clinical setting is a common practice and appears to be relatively safe, research on alternative routes of administration is needed to provide potentially less harmful alternative routes of administration in heroin-assisted treatment.

The suitability of oral diacetylmorphine in treatment-refractory patients with heroin dependence: A scoping review.

OBJECTIVE: To review the scientific literature on the pharmacokinetics, pharmacodynamics and clinical efficacy and safety of (supervised) oral diacetylmorphine for patients with severe heroin dependence. METHODS: The PubMed, Embase, Web of Science and PsycINFO databases were searched. Eleven published studies were identified and selected based on defined eligibility and exclusion criteria. RESULTS: Four pharmacokinetic studies reported negligible plasma concentrations of diacetylmorphine and its active metabolite 6-monacetylmorphine. Among six pharmacodynamic studies, three trials showed that oral diacetylmorphine reduced opioid withdrawal symptoms, one open-label pilot study reported that two patients experienced a modest 'rush' after oral diacetylmorphine and two studies found that patients could not distinguish between oral diacetylmorphine, methadone, or morphine. Regarding the clinical studies, a Swiss prospective cohort study in patients with heroin dependence showed high retention rates of oral diacetylmorphine treatment with few serious adverse events, whereas in the Canadian SALOME trial, oral diacetylmorphine treatment was prematurely discontinued because treatment retention of oral diacetylmorphine was lower than injectable diacetylmorphine maintenance treatment. Finally, two case studies illustrate the limitations and potential problems of oral diacetylmorphine in the treatment of treatment-refractory heroin dependent patients. CONCLUSIONS: Based on all published data, it is unlikely that oral diacetylmorphine produces a substantial 'rush'. Prescription of oral diacetylmorphine might therefore be effective only for treatment-refractory patients with heroin dependence (i) as maintenance treatment for those who never injected or inhaled opioids; (ii) as maintenance treatment for those who want to switch from injection to oral administration of diacetylmorphine; and/or (iii) to reduce opioid withdrawal symptoms.

Alcohol trajectories and subsequent risk for opioid misuse in a cohort of urban adolescents.

Background: The opioid epidemic is a public health emergency in the US. Alcohol is the most widely used addictive substance among all age groups; however, the contribution of different alcohol use trajectories throughout adolescence and young adulthood to the development of opioid misuse in young adulthood among urban minority youth has not been investigated. Methods: Data are from a study of 580 youth (85% African American, 67% low SES) residing in Baltimore City followed from ages 6-26. Alcohol trajectories were identified between ages 14 and 26 using group-based trajectory modeling. Opioid misuse was defined as using opioid painkillers without a prescription or using heroin between ages 19 and 26. Opioid misuse outcomes were also investigated separately. Logistic regression examined associations of alcohol trajectories with opioid misuse in young adulthood adjusting for socio-demographics, early use of tobacco and cannabis, neighborhood, and peer factors. Results: Six alcohol use trajectories were identified: Young adult increasing (21.4%), adult increasing (19.1%), abstaining (19.1%), experimenting (15.3%), adolescent increasing (14.8%), and adolescent limited (10.2%). In models fully adjusted for covariates, relative to the abstaining trajectory, the adolescent increasing trajectory was associated with an elevated risk of opioid misuse (aOR = 3.3, 95%CI = 1.4, 7.8) and prescription opioid misuse (aOR = 3.9, 95%CI = 1.4, 10.8) in young adulthood. Conclusions: Escalating alcohol use in adolescence and young adulthood is associated with an elevated risk of opioid misuse in young adulthood in a cohort of predominantly African American and socio-economically disadvantaged young people. Tailored interventions should target high levels of alcohol use during these developmental periods to reduce risk for opioid misuse among disadvantaged youth.