BACKGROUND: While randomized-controlled trials have shown that heroin-assisted treatment (HAT) is superior to methadone maintenance alone in treatment of refractory clients, little is known about client factors associated with retention in HAT in routine care.
METHODS: This retrospective cohort study assessed predictors of retention in first treatment episode among a consecutive cohort of clients admitted to HAT in Denmark from 2010 to 2018, who could be matched to the Danish population register and for whom a Short Form Health Survey (SF-36) was available at admission (N = 432). The study derived predictors from client self-reports at intake and administrative data available in national registers. Cox proportional hazards regression modelled retention in treatment.
RESULTS: The one-year retention rate was 69.63 % (95 % CI 65.06 %-73.74 %), and the median time in treatment was 2.45 years (95 % CI, 1.83-3.12). Bivariate analyses showed that retention was lower for clients who had recent cocaine or benzodiazepine use and among those who had experienced an overdose in the year prior to enrollment in HAT. Age below 40, recent illegal activity, poorer emotional wellbeing, previous residential treatment experience, and previous intensive outpatient treatment were also predictors of dropout from HAT.
CONCLUSIONS: This observational study found that retention in HAT in routine care was similar to rates observed in randomized-controlled trials conducted in other countries. The results suggest that addressing polysubstance use as part of the HAT program may promote long-term retention, as may directing resources to certain subgroups identified at intake, including clients under 40 years and those who report recent criminal activity, emotional problems, or overdoses. The findings that previous residential treatment and intensive outpatient treatment were associated with dropout were unexpected.

Drug dependence is a chronic brain disease characterized by craving and recurrent episodes of relapse. Tramadol HCl is a promising agent for withdrawal symptoms management, considering its relatively low abuse potential and safety. Oral administration, however, is not preferred in abstinence maintenance programs. Introducing an implantable, long-lasting formula is suggested to help outpatient abstinence programs achieve higher rates of treatment continuation. Tramadol implants (T350 and T650) were prepared on polycaprolactone polymer ribbons by the wet method. Male Wistar rats were adapted to heroin-conditioned place preference (CPP) at escalating doses (3-30 mg/kg, intraperitoneally, for 14 days). Implants were surgically implanted in the back skin of rats. After 14 days, the CPP score was recorded. Naloxone (1 mg/kg, intraperitoneally) was used to induce withdrawal on day 15, and symptoms were scored. Elevated plus maze and open field tests were performed for anxiety-related symptoms. Striata were analyzed for neurochemical changes reflected in dopamine, 3,4-dihydroxyphenyl acetic acid, gamma-aminobutyric acid, and serotonin levels. Brain oxidative changes including glutathione and lipid peroxides were assessed. The tramadol implants (T350 and T650) reduced heroin CPP and limited naloxone-induced withdrawal symptoms. The striata showed increased levels of 3,4-dihydroxyphenyl acetic acid, and serotonin and decreased levels of gamma-aminobutyric acid and dopamine after heroin withdrawal induction, which were reversed after implanting T350 and T650. Implants restore the brain oxidative state. Nonsignificant low naloxone-induced withdrawal score after the implant was used in naive subjects indicating low abuse potential of the implants. The presented tramadol implants were effective at diminishing heroin CPP and withdrawal in rats, suggesting further investigations for application in the management of opioid withdrawal.

Prior studies have shown that individuals and their peers often have similar substance use behaviors, but the mechanisms driving these similarities - particularly in rural settings, are not well understood. The primary objectives of this analysis are to (1) identify factors that contribute to relationship turnover and maintenance within a rural network of persons who use drugs (PWUD), (2) determine whether assimilation and/or homophily shape participants use of injection drugs, heroin, and stimulants (methamphetamine and cocaine), and (3) assess the extent that these mechanisms influence networks ties and/or behaviors and whether these effects vary across time.
Sociometric network data were collected from a cohort of PWUD in rural Eastern Kentucky at baseline (2008-2010) and at four follow-up visits conducted approximately semiannually. Stochastic actor-oriented models (SAOMS) were used to model network structure and participant behaviors as jointly dependent variables and to identify characteristics associated with the maintenance, dissolution, and formation of network ties and changes in drug use behaviors.
Findings suggest (1) greater network stability over time for reciprocal and transitive relationships, (2) both homophily and assimilation played a greater role in shaping injection drug use (IDU) initiation and cessation than they did in shaping heroin and stimulant use, and (3) the importance of these mechanisms appeared consistent over time.
Given the stability of particular network structures and evidence of both homophily and assimilation with respect to drug-use behaviors, interventions that leverage social networks could be used to motivate health-promoting behaviors.

OBJECTIVE: Legal regulations for dispensing in Swiss heroin-assisted treatment were relaxed during the COVID-19 pandemic, allowing prolonged take-home of up to 7 days instead of two to reduce patient contact and the risk of infection. Our study aimed to measure the consequences of this new practice.
METHODS: This was a retrospective cohort study set in Switzerland\'s largest outpatient centre for opioid agonist therapy. One hundred and thirty-four (72.4%) of the 185 patients receiving oral diacetylmorphine (DAM) participated in the study.
METHODS: Through the utilization of electronic medication prescription and dispensing software, as well as the electronic medical record, the following data were extracted to explore the potential consequences: dose of DAM, the number of antibiotic therapies, emergency hospitalizations and incarcerations. Age, gender, prescriptions for psychotrophic drugs and additional prescription for injectable DAM were tested to assess an increased risk of losing prolonged take-home privileges. Data in the year since prolonged take-home (period 2) were compared with data from the equivalent prior year (period 1).
RESULTS: DAM take-home was not associated with a change in DAM dose (P = 0.548), the number of emergency hospitalizations (P = 0.186) or the number of incarcerations (P = 0.215); 79.1% of all patients were able to maintain their extended take-home privileges. However, patients who had injectable DAM experienced significant reductions in their prolonged take-home privileges.
CONCLUSIONS: Allowing patients to take home oral diacetylmorphine for up to 7 days as treatment for opioid use disorder does not appear to pose any demonstrable health risk. It is generally manageable for the large majority of patients. However, careful consideration of prolonged take-home for patients with additional injectable diacetylmorphine is recommended, as these patients are more likely to lose take-home privileges.

Addiction is a chronic disorder that comes with emotional and financial burdens. Several neurobiological factors were correlated to opiate-use disorder which is brain-derived neurotrophic factor (BDNF). BDNF has been found to be involved in long-term potentiation of synaptic strength, a mechanism that is thought to motivate both natural adaption mechanisms as well as the development of addictive behavior. In this study, we aimed to address the relation between BDNF serum level and heroin craving and the effect of duration of abstinence on them.
A case study was conducted on 80 subjects from Kasr Al-Ainy Psychiatry and Addiction Treatment Hospital with a history of heroin dependence and were divided into two groups: Group A had 40 active heroin-dependent subjects while in Group B, 40 subjects with 1-year heroin abstinence. Severity of addiction was assessed by the addiction severity index, heroin craving was measured by Brief Substance Craving Scale and serum BDNF level was investigated using an enzyme-linked immunosorbent assay.
The findings show that active heroin users had significantly higher serum BDNF which is associated with high heroin craving in comparison to the abstinent group.
This study revealed a significant positive correlation between serum BDNF levels and craving in active heroin users versus 1-year abstinent subjects. It is the first study to address the relationship between craving and serum BDNF level in a 1-year abstinent participants. These findings help to determine the brain alterations associated with illness and recovery in heroin dependence.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

Increasing evidence suggests that heroin addiction may be related to the dysfunction among the triple brain network (default mode network [DMN], salience network [SN] and executive control network [ECN]). However, the characteristics of glucose metabolism and metabolic connectivity among core regions of the triple brain network remain unknown. Therefore, we hypothesized that individuals with heroin dependence would show abnormal glucose metabolism and accompanied abnormal metabolic connectivity within the triple brain network.
Individuals with heroin dependence and healthy controls matched for age and sex underwent integrated positron emission tomography/magnetic resonance imaging (PET/MRI). Differences in glucose metabolism and metabolic connectivity among the DMN, SN and ECN were analyzed based on 18F-fluorodeoxyglucose PET and resting-state fMRI data.
We included 36 individuals with heroin dependence and 30 matched healthy controls in our study. The heroin dependence group showed a significant reduction of glucose metabolism in the bilateral anterior insula (AI) and inferior parietal lobule (IPL), and a significantly decreased metabolic connectivity between the right AI and the left dorsolateral prefrontal cortex (DLPFC). The daily dose of methadone was negatively correlated with glucose metabolism of the right AI and right IPL.
The results revealed the glucose metabolism alterations and metabolic connectivity only within the triple brain network in individuals with heroin dependence; additional brain networks should be investigated in future studies. Although methadone is an opioid with a similar neurophysiological mechanism as heroin, the specific chronic effects of methadone on cerebral metabolism and metabolic connectivity should also be investigated in future studies.
Our findings suggest that long-term opioid use might, to some extent, be associated with reduced synergistic ability between the SN and ECN, which may be associated with the dysfunction of cognitive control. In particular, the right AI, which showed hypometabolism and related reduction in SN-ECN metabolic connectivity, should receive increasing attention in future studies.

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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.
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.
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.
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.

For the past two decades, the USA has been embroiled in a growing prescription drug epidemic. The ripples of this epidemic have been especially apparent in the state of Maine, which has fought hard to mitigate the damage caused by addiction to pharmaceutical and illicit opioids. In this study, we construct a mathematical model of the opioid epidemic incorporating novel features important to better understanding opioid abuse dynamics. These features include demographic differences in population susceptibility, general transmission expressions, and combined consideration of pharmaceutical opioid and heroin abuse. We demonstrate the usefulness of this model by calibrating it with data for the state of Maine. Model calibration is accompanied by sensitivity and uncertainty analysis to quantify potential error in parameter estimates and forecasts. The model is analyzed to determine the mechanisms most influential to the number of opioid abusers and to find effective ways of controlling opioid abuse prevalence. We found that the mechanisms most influential to the overall number of abusers in Maine are those involved in illicit pharmaceutical opioid abuse transmission. Consequently, preventative strategies that controlled for illicit transmission were more effective over alternative approaches, such as treatment. These results are presented with the hope of helping to inform public policy as to the most effective means of intervention.