Background Research on depression and persistent mental distress in individuals with opioid use disorder (OUD) during and post-treatment with extended-release naltrexone (XR-NTX) is limited. Methods The NaltRec study, a naturalistic, multicenter, open-label clinical trial, were conducted in Norwegian hospitals from September 2018 to October 2022. Participants received XR-NTX injections for up to 52 weeks, followed by a 52-week post-treatment period. Outcome measures were assessed using Mini International Neuropsychiatric Interview, Montgomery-Åsberg Depression Rating Scale-Self rating, and items from the European version of the Addiction Severity Index. A growth mixture model (GMM) was employed to identify distinct subgroups of depressive symptoms, while between-subgroup differences in mental distress were evaluated using a generalized linear mixed model (GLMM). Results The population had a mean age of 37.8 years (SD 9.7), 24.1% were female, mean (SD, min-max) MADRS-S score were 15.0 (8.9, 0–41) at baseline. Subgroups were identified by the GMM: Group 1 (G1) with no to very mild depressive symptoms (69.5%) and Group 2 (G2) with moderate depressive symptoms (30.5%). G2 reported more frequent mental health conditions compared to G1 at baseline. Both subgroups presented decreasing depressive symptoms through the study period. Secondary outcome analysis showed G1 maintained low and stable mental distress levels, while G2 exhibited higher levels and increased odds of mental distress. Conclusion This study emphasizes the importance of comprehensive mental health assessments and continuous distress monitoring in individuals undergoing XR-NTX treatment. Although distress decreased, ongoing support seems essential to sustain improvements post-treatment, informing more effective protocols for those with OUD.

Background: Previous research has linked opioid use disorder (OUD) to neuronal reward systems and impulsivity. The aim of this study was to examine the influence of COMT rs4680 Val158Met polymorphism on impulsivity, hyperactivity and inattention (IHI) in patients with OUD. Methods: Open-label, cross-sectional cohort study was conducted involving individuals, 18 to 65 years, with OUD who either were included in opioid agonist treatment (OAT)—or same group of individuals who were awaiting induction on extended-release naltrexone (XR-NTX). Adult ADHD Self-Report Scale 18-item version was used to score IHI, and saliva samples were collected for genotyping (TaqMan assays). Logistic regression models were used to analyze the data. Results: The data of the entire cohort (n = 206) showed that carriers of one or two Val alleles had a negative association with IHI compared to Met/Met carriers (Val/Met OR = 0.43, p-value = 0.017, and Val/Val OR = 0.29, p-value = 0.005). Individuals included in OAT not waiting for XR-NTX (n = 120) exhibited the same pattern as observed in the entire cohort (Val/Met OR = 0.33, p-value = 0.019, and Val/Val OR = 0.18, p-value = 0.004), but not those who chose XR-NTX (Val/Met OR = 0.60, p-value = 0.353, and Val/Val OR = 0.47, p-value = 2.779). Conclusions: The present study revealed that individuals with OUD carrying the COMT rs4680 Val allele had lower IHI scores than Met/Met carriers. Hence, in individuals with OUD, the COMT rs4680 Met allele is associated with higher IHI symptom burden.

BACKGROUND:This study investigates changes in quality of life (QoL) among individuals with opioid use disorder (OUD) undergoing extended-release naltrexone (XR-NTX) treatment for 52 weeks, subsequent by a 1-year post-treatment period. METHODS:Conducted as a naturalistic, multicenter, open-label clinical trial across five urban hospitals in southern Norway, this observational study enrolled 158 participants with severe OUD. Participants received XR-NTX treatment for up to 52 weeks, with QoL assessed using the WHOQOL-BREF instrument at five time points during treatment and twice during the post-treatment period. The Addiction Severity Index, European version (EuropASI) was used to measure covariates. A linear mixed model was employed to analyze trends in QoL, adjusting for mental distress severity and substance use severity. RESULTS:Significant improvements in QoL were observed in the physical, psychological, social and environmental domains during the XR-NTX treatment, with less pronounced changes in the environmental domain. Mental distress and substance use severity were negatively associated with QoL scores. The most substantial QoL improvements occurred within the first year of treatment, with overall perceived QoL remaining stable during the 1-year post-treatment period. CONCLUSIONS:This study highlights XR-NTX as a beneficial treatment option for enhancing QoL in individuals with OUD. The findings support the integration of XR-NTX into OUD treatment plans and emphasize the need for further research to explore long-term outcomes and the impact of external factors on QoL.

Background. Disrupted reward processing is a core component in neurobiological theories of addictions, including opioid use disorder (OUD). While acute opioid agonist and antagonist administration can modulate reward behavior and experiences, it remains unclear how typical long-term OUD treatment with these medications impact patients’ sensitivity to substance-free rewards. We therefore conducted a cross-sectional study of reward sensitivity in opioid agonist- and antagonist-treated OUD patients, and healthy volunteers.Methods. Ninety-six OUD patients on extended-release naltrexone (n=45) or opioid agonists (n=51) and 50 healthy volunteers completed a probabilistic reward task (PRT) and self-report measures of anhedonia, depression, preoccupation with immediate consequences, substance craving and life satisfaction in a single session. We used signal detection analysis and drift diffusion modeling to derive behavioral reward bias measures from PRT performance. Group differences were modeled with beta and linear regression.Results. Patients reported significantly greater anhedonia (Cohen’s ds≥0.64), depression (ds≥0.53) and preoccupation with immediate consequences (ds≥0.54) than heathy volunteers, but differences between naltrexone- and opioid agonist-treated patients were non-significant (ds≤0.26). Group differences in behavioral reward bias were small and non-significant (ps=1, BF01s≥84.13). Anhedonia was significantly associated with lower life satisfaction (OR [95% CI]=1.10 [1.04, 1.17]). There were no other significant associations between reward sensitivity measures and life satisfaction or craving (ps≥0.31, BF01s≥2.58).Conclusion. These data support an association between OUD and reduced well-being irrespective of opioid agonist or antagonist treatment, highlighting patients’ need for psychosocial support and/or adjunct interventions. Major detrimental effects of naltrexone treatment on well-being seem unlikely from these and previous results.

INTRODUCTION:Personal recovery is an important target in mental health care settings and has been suggested as the "bridging principle" between mental health care and substance use disorder (SUD) treatment. However, few psychometrically evaluated scales exist for measuring personal recovery in SUD research, and the questionnaire about the process of recovery (QPR), a measure of personal recovery widely used in the mental health field, has not been previously psychometrically evaluated in such a context. The aim of this study was to explore the psychometric properties of the 22- and 15-item versions of the Norwegian translation of the QPR in terms of factor structure and internal consistency in an opioid use disorder (OUD) sample. METHODS:A total of 156 people with OUD filled out the QPR. Exploratory factor analysis with principal axis factor and maximum likelihood as extraction method was performed to assess the dimensionality of the 22- and 15-item versions of the Norwegian translation of the QPR. Internal consistency was calculated according to Cronbach's alpha. RESULTS:Internal consistency for the 22-item version was α = 0.917. After removal of three items with low factor loadings internal consistency was α = 0.922. Internal consistency for 15-items version was α = 0.915. Exploratory factor analyses showed a clear one-factor solution for both the 22-item and 15-item version. CONCLUSION:Both the 15- and the 22-item versions of QPR showed a clear one-factor solution; however, the 15-item version showed the strongest results in terms of explained variance. Thus, the 15-item version is the recommended version to use in SUD samples.

Background. Opioid use disorder (OUD) treatment mainly involves long-term use of medications that either stimulate (agonists) or block (antagonists) mu-opioid receptors and that could potentially affect patients’ experiences of pain. We therefore conducted an observational study of pain symptoms and sensitivity in patients receiving opioid agonist and antagonist treatment for OUD, and healthy volunteers.Methods. Seventy-four OUD patients receiving the antagonist extended-release naltrexone (XR-NTX; n = 34) or opioid agonists (methadone or buprenorphine; n = 40), as well as 50 healthy volunteers participated in a single study session. Participants answered questions about their current pain symptoms, and completed a Cold Pressor Test (CPT) while we measured heart rate and salivary cortisol. Hypotheses and analyses were preregistered before data access. Group differences in chronic pain rates and cold pain responses were modeled with logistic, beta and linear regression and tested with likelihood ratio χ2- and F-tests.Results. Half of patients in either treatment reported living with chronic pain. Individual CPT responses were variable. Patients on opioid agonists and XR-NTX reported pain 2 and 9 seconds earlier than and removed their hand 34 and 46 seconds before healthy volunteers. These group differences align with prior findings of heightened pain sensitivity in agonist-maintained patients but were non-significant (ps = 1). Differences in cold pain intensity and cold pain-induced changes in heart rate and cortisol aligned with hypotheses but were also non-significant (ps ≥ 0.17). Conclusion. Consistent with prior observations, the current findings indicate that a considerable number of OUD patients experience persistent pain symptoms while undergoing either opioid agonists or XR-NTX treatment. Major detrimental or beneficial effects of these medications on pain and pain sensitivity seem unlikely however.

BACKGROUND:Previous work found a decrease in lysophosphatidylcholines (LPCs) in fibromyalgia (FM) serum, prompting the hypothesis that this decrease could be due to increased conversion of LPC to lysophosphatidic acid (LPA) through autotaxin (ATX). LPA has pronociceptive functions, and increased LPA levels could modulate FM pain. METHODS:This study quantified LPA levels in serum and lumbar cerebrospinal fluid (CSF) and serum ATX levels in FM patients, comparing with healthy controls (HCs), osteoarthritis (OA), degenerative disc disease (DDD) and lumbar disc herniation (LDH) patients. RESULTS:We found increased serum LPA levels in FM and OA patients, with no changes in FM lumbar CSF. Unexpectedly, a positive correlation between serum LPA and conditioned pain modulation was observed in FM patients, while LPA levels were correlated with pain intensity and Knee Injury and Osteoarthritis Outcome Scores in OA. Serum ATX levels in FM patients were comparable to those in HC but correlated significantly with FM LPA levels (in one cohort), as well as with pain duration and the maximal weekly pain intensity. CONCLUSIONS:This study suggests that increased LPA levels play distinct roles in FM and OA patients. In FM, LPA levels were linked to less impaired inhibitory pain pathways, while LPA levels in OA correlated with pain intensity and knee-related impairment. ATX levels in FM serum are associated with pain intensity and duration. These findings underscore the complex role of LPA and ATX in FM pathophysiology. Future studies are essential to clarify LPA's specific roles and to develop therapies. SIGNIFICANCE STATEMENT:This study provides novel insights into the role of LPA in FM and other chronic pain conditions. Although ATX levels were unchanged in FM, a positive correlation between serum ATX and LPA supports the role of ATX in LPA conversion. These findings suggest complex lipid dysregulation in FM, with LPA potentially modulating pain pathways. Further research is needed to clarify LPA's role and its potential as a biomarker or therapeutic target.

Background Mental health status may be improved in patients receiving treatment with the opioid antagonist extended-release naltrexone (XR-NTX), but longer-term outcomes remain unexamined. Objectives This study aims to assess changes in symptoms of anxiety, depression, and insomnia among opioid-dependent individuals in long-term treatment with XR-NTX and to explore possible associations between such symptoms and the use of illicit opioids. Methods: After completing an initial 3-month randomized clinical trial and an extended 9-month follow-up study, 50 opioid-dependent individuals (9 women) chose to continue treatment with XR-NTX at their own discretion for a prolonged period of up to 2 years. Symptoms of anxiety, depression, and insomnia were assessed every 4th week. In addition, the participants reported use of illicit opioids. Results The participants reported improved mental health status during up to 3 years treatment with XR-NTX. Symptoms of anxiety and depression were reduced from mean 18.0 (SD:6.1) to 12.3 (SD:4.4) (p < 0.001), and from 30.5 (SD:9.1) to 17.8 (SD:5.4) (p < 0.01), respectively, whereas symptoms of insomnia were reduced from 14.2 (SD:7.9) to 3.6 (SD:3.6), (p < 0.001). The reduction in these symptoms was more pronounced in participants who did not relapse to opioid use (n = 35) during the study. Conclusion Long-term treatment with XR-NTX may promote a reduction in symptoms of anxiety, depression, and insomnia in opioid-dependent individuals. Those who managed to stay abstinent from opioids were likelier to experience a greater reduction in symptoms compared to those who relapsed to opioid use during the 3-year treatment period.Clinicaltrials.gov no. NCT01717963

Purpose:To examine whether reported pain intensity over time is related to the single nucleotide polymorphisms of the catechol-O-methyltransferase (COMT rs4680) and mu-opioid receptor (OPRM1 rs1799971) in patients with opioid use disorder (OUD) choosing treatment with extended-release naltrexone (XR-NTX) or opioid agonist treatment (OAT). Patients and Methods:This exploratory study was part of a 24-week, open-label clinical prospective trial of patients with OUD who chose intramuscular XR-NTX, and patients receiving OAT. Men and women aged 18 to 65 years with OUD per the Diagnostic and Statistical Manual of Mental Disorders, fifth edition were included. Pain intensity was measured at baseline and at 24-week follow-up using the Numerical Pain Rating Scale-11 and genotyping was performed by TaqMan technology. Data were analyzed with ordinal logistic regression. Results:Of 317 participants included at baseline, 210 samples were obtained and analyzed. In the OAT group, there was a negative significant association between pain intensity and having the Val/Val allele of COMT rs4680 (wild-type = most common type) and the rare allele G of OPRM1 rs1799971 at 24-week follow-up. No such effects were seen in the XR-NTX group. Conclusion:The wild-type allele Val/Val of COMT rs4680 and the rare allele G of OPRM1 rs1799971 may have a possible protective effect regarding pain intensity in patients with OUD receiving OAT. Given relatively low sample size, particularly low number of female participants in the XR-NTX group and other possible confounders, our findings should be interpreted with caution.

BACKGROUND AND OBJECTIVES:Extended-release naltrexone (XR-NTX) is an opioid antagonist effective for treating opioid use disorder (OUD). However, concerns about inadequate pain management may limit its use. This study will examine changes in pain intensity in OUD patients choosing XR-NTX compared to opioid agonist treatment (OAT), identify subgroups with distinct pain intensity trajectories, and assess the effect of pain intensity on XR-NTX treatment outcomes (retention, relapse, opioid use, and cravings). METHODS:This 24-week study included OUD patients aged 18-65 years opting for XR-NTX (n = 160). Patients receiving OAT (n = 151) served as controls. Pain intensity was measured every 4 weeks for XR-NTX and at baseline and Week 24 for OAT using the numerical pain rating scale-11 (NPRS-11). Data were analyzed with linear mixed models and group-based trajectory modeling. RESULTS:Between baseline and Week 24, XR-NTX participants with low to moderate pain showed a significant reduction in pain intensity, while those with high pain did not. In the OAT group, no significant reduction in pain intensity was observed (from baseline to Week 24). Pain intensity was not associated with XR-NTX treatment outcomes. DISCUSSION AND CONCLUSIONS:Contrary to perception, XR-NTX does not worsen pain intensity, nor did pain intensity affect XR-NTX treatment outcomes. SCIENTIFIC SIGNIFICANCE:This study is the first to explore the association between changes in pain intensity and XR-NTX treatment outcomes in OUD patients over a 24-week period. The findings challenge the perception that XR-NTX is less suitable for treating OUD patients with pain.

BackgroundChronic pain conditions and posttraumatic stress disorder (PTSD) are highly prevalent among patients with substance use disorders (SUDs). Both can impact outcomes of SUD treatment and quality of life. There is a need for a large-scale study on the overlap of and interactions between SUD, chronic pain, and PTSD. ObjectiveThe Norwegian Addiction, Pain and Trauma study (NOR-APT) is the first longitudinal study to describe how substance use and outcomes of SUD treatment are impacted by (1) chronic pain and pain characteristics and (2) interactions between comorbid chronic pain and PTSD. MethodsSelf-reported questionnaire data were collected from patients in all types of SUD treatment at four hospital sites in Norway. The questionnaire data on substance use, pain, and posttraumatic stress symptoms will be combined with retrospective and prospective longitudinal data from high-quality demographic and health registries. The registry data cover, for example, treatment episodes, diagnoses, and prescribed medications and socioeconomic variables, with a follow-up period of altogether 20 years (approximately 2008-2029). ResultsQuestionnaire data were collected during March 2021-June 2024. Altogether 1890 patients were approached, and 1645 (87%) questionnaires were completed. The estimated final sample size pending data cleaning (eg, removal of duplicates and validation of consent forms) is 1400-1500. Linkage of registry data for approximately 1000 with valid ID numbers and consent is planned for 2026 (retrospective) and 2029/2030 (prospective). At least 10 publications are planned in the period 2025-2028, based on funding received from the Foundation Dam, the Norwegian Research Council, Akershus University Hospital, and Oslo University Hospital. We plan to apply for further funding related to the use of the prospective registry data. ConclusionsResults from the NOR-APT study will contribute to a better understanding of SUD, chronic pain and PTSD comorbidities, their interactions, trajectories and impact on SUD treatment outcomes, and subjective quality of life. Results can also contribute knowledge toward the development and assessment of treatment interventions that can improve SUD treatment outcomes. Trial RegistrationClinicalTrials.gov NCT04908410; https://clinicaltrials.gov/study/NCT04908410 International Registered Report Identifier (IRRID)DERR1-10.2196/67663

For people with opioid use disorder (OUD), extended-release naltrexone (XR-NTX) is an effective antagonist treatment option. However, successful opioid tapering and abstinence is a prerequisite for XR-NTX induction and has repeatedly been reported as a major barrier to effective treatment. The aims of this study were to describe XR-NTX induction rates, reasons for incomplete induction, and extraordinary complications reported during the induction phase. We also compared sociodemographic and clinical variables among those who did and did not complete induction onto XR-NTX. This naturalistic, multicenter, and open-label Norwegian study of XR-NTX included men and women aged 18–65 who had severe OUD. Most participants were referred to inpatient medically managed opioid withdrawal and received individualized pharmacological and psychosocial treatment according to clinical assessment and national guidelines. After opioid withdrawal, the participants underwent a minimum of three opioid-free days prior to XR-NTX induction. Variables were collected through baseline assessments and a retrospective patient chart review. XR-NTX induction completers and non-completers were compared via bivariate and logistic regression analyses. Of 129 participants with recent opioid use at inclusion, 106 (82 clinicaltrials.gov (NCT03647774).

Background/Objectives: The variation in the treatment outcomes of extended-release naltrexone (XR-NTX) including the potential role of genetic factors are poorly understood. This study aimed to explore the potential association between the catechol-O-methyltransferase (COMT) rs4680 and mu-opioid receptor (OPRM1) rs1799971 genotypes and XR-NTX treatment outcomes in patients with opioid use disorder (OUD) specifically focusing on treatment retention, relapse to opioids, number of days of opioid use, and opioid cravings. Methods: This was a 24-week, open-label clinical prospective, exploratory study involving patients with OUD who chose treatment with monthly injections of intramuscular XR-NTX. Men and women aged 18-65 years with OUD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were included. The participants were interviewed using the European Addiction Severity Index. Survival analyses and linear mixed models were used to analyze the data. Results: Of the 162 participants included in this study, 138 (21% female) initiated treatment with XR-NTX, with 88 genotyped for COMT rs4680 and 86 for OPRM1 rs1799971. Heterozygous Met/Val carriers of COMT rs4680 were less likely to relapse to opioids compared with those with the COMT rs4680 Met/Met genotype. No significant association was observed for the OPRM1 polymorphism. Conclusions: Patients with the COMT rs4680 Met/Val genotype exhibit a reduced risk of relapse to opioids and may therefore derive greater benefit from XR-NTX treatment compared with those with the COMT rs4680 Met/Met genotype. Future studies should be conducted with a larger number of participants and possibly include other genetic variants and treatment outcomes. The trial is registered at ClinicalTrials.gov (#NCT03647774) and the EU Clinical Trial Register (#2017-004706-18).

Introduction: The treatment efficacy of extended-release naltrexone (XR-NTX) for opioid use disorder (OUD) has been demonstrated in several studies, but not in naturalistic settings where opioid agonist treatment (OAT) is freely accessible. This study aimed to examine the different treatment outcomes of XR-NTX in a setting where the participants freely chose XR-NTX as a treatment option instead of OAT. Methods: This was a 24-week open-label clinical prospective cohort study conducted in an outpatient setting at five hospitals in Norway. The study included 161 participants aged 18-65 years with OUD. Intramuscular injections of XR-NTX were administered every 4 weeks for 24 weeks. Measurements included retention in treatment, reasons for treatment discontinuation, days of use of opioids, other illicit substances and alcohol, level of heroin craving, treatment satisfaction, and adverse events (AEs). Results: Of 161 included participants, the mean age was 38 years, and 24% were women; 138 received at least one dose of the study medication (modified intention-to-treat [MITT] population), and mean time in treatment was 18.1 weeks (95% CI: 16.8-19.4). The majority of the MITT population (84; 60.9%) completed 24 weeks of treatment in the study. There was a significant decrease in the overall use of opioids (p < 0.001) and the use of alcohol, and other illicit substances were low. The participants generally reported high treatment satisfaction and low heroin cravings. Those who completed the 24 weeks of treatment reported significantly fewer days of opioid use (p < 0.001) and higher treatment satisfaction (p < 0.001) than those who discontinued treatment before 24 weeks. No serious AEs were directly related to XR-NTX use. Conclusion: This study demonstrated high retention rates, decreased opioid use, and low use of other illicit substances and alcohol. Participants also reported low cravings for heroin and high treatment satisfaction. Completion of the full 24-week treatment resulted in lower opioid use and increased treatment satisfaction compared to those who discontinued treatment before 24 weeks. The observed higher retention and reduced opioid use, compared to other studies, may be attributed to participants' strong motivation for opioid abstinence facilitated by XR-NTX treatment. (c) 2024 The Author(s). Published by S. Karger AG, Basel

Background We aimed to evaluate the efficacy of opportunistic treatment of hepatitis C virus (HCV) infection among hospitalized people who inject drugs (PWID).Methods We performed a pragmatic, stepped wedge cluster randomized trial recruiting HCV RNA positive individuals admitted for inpatient care in departments of internal medicine, addiction medicine, and psychiatry at three hospitals in Oslo, Norway. Seven departments were sequentially randomized to change from control conditions (standard of care referral to outpatient care) to intervention conditions (immediate treatment initiation). The primary outcome was treatment completion, defined as dispensing the final package of the prescribed treatment within six months after enrolment.Results A total of 200 HCV RNA positive individuals were enrolled between 1 October 2019 and 31 December 2021 (mean age 47.4 years, 72.5% male, 60.5% injected past 3 months, 20.4% cirrhosis). Treatment completion was accomplished by 67 of 98 (68.4% [95% confidence interval {CI}: 58.2-77.4]) during intervention conditions and by 36 of 102 (35.3% [95% CI: 26.1-45.4]) during control conditions (risk difference 33.1% [95% CI: 20.0-46.2]; risk ratio 1.9 [95% CI: 1.4-2.6]). The intervention was superior in terms of treatment completion (adjusted odds ratio [aOR] 4.8 [95% CI: 1.8-12.8]; P = .002) and time to treatment initiation (adjusted hazard ratio [aHR] 4.0 [95% CI: 2.5-6.3]; P < .001). Sustained virologic response was documented in 60 of 98 (61.2% [95% CI: 50.8-70.9]) during intervention and in 66 of 102 (64.7% [95% CI: 54.6-73.9]) during control conditions.Conclusions An opportunistic test-and-treat approach to HCV infection was superior to standard of care among hospitalized PWID. The model of care should be considered for broader implementation.

Background: Opioid dependency is a risk factor for several negative life events and conditions. The opioid receptor inhibitor extended-release naltrexone (XR-NTX) is safe and effective in reducing illicit substance use. Here, we report results of a naturalistic, multicentre, open-label trial of XR-NTX for 24 weeks, with an optional 28-week treatment extension (NaltRec study). Aims: The study aims were to compare sociodemographic and clinical variables between patients choosing XR-NTX (n=162) and those in opioid agonist treatment (OAT) (n=155), and to compare these variables in the XR-NTX group between patients who were (n=103) and were not (n=59) in OAT before study inclusion. Methods: To measure objective-related factors, we used a structured interview at inclusion. Results: The XR-NTX group had fewer women, was younger and reported poorer living and social conditions than the OAT group. Both groups had serious health conditions. Across groups, 40% percent reported lifetime suicide attempts, and 60% reported abusive experiences, with 47% women and 17% men reporting sexual abuse. Age at onset of polydrug use was 20 years. Patients preferring XR-NTX to OAT reported poorer social conditions compared with those choosing OAT. Conclusions: Women and patients who are not stabilized before enrolment need specific attention to tailored supportive measures during treatment with extended-release naltrexone.

Background and aims: Recovery from substance use disorders (SUD) has traditionally been equated with abstinence. "Personal recovery" however emphasizes recovery as a unique and personal process, supported by changes in connectedness, hope, identity, meaning and empowerment. This study aimed to examine personal recovery in people receiving extended-release naltrexone (XRNTX); specifically investigate changes in personal recovery during treatment, identify groups of participants following distinct trajectories of recovery, and characteristics predicting groupbelonging.Methods: Overall change in recovery (Questionnaire about the Process of Recovery, QPR) score was assessed by linear mixed model in a subsample of 135 people with opioid use disorder (OUD) participating in a 24 + 28-week trial of XR-NTX. Growth mixture model was used to identify potential groups of people following distinct trajectories of personal recovery.Results: Overall, there was a significant change in QPR score during treatment. Four groups with distinct recovery trajectories were identified: "initially low- increase" (G1), "initially average- no change" (G2), "initially high- no change" (G3) and "initially high- increase" (G4). The groups were different with regards to level of psychological distress, social support, and the use of benzodiazepines. In addition, previous participation in opioid agonist treatment programs, current pain, life satisfaction, employment, heroin craving and previous use of heroin also differed between groups.Conclusions: Personal recovery among people receiving XR-NTX follows different trajectories, and various factors are associated with personal recovery. Particular attention regarding psychological distress, social support and heroin use among patients commencing XR-NTX treatment is important to facilitate successful recovery trajectories.

Background and objective: This is the first study to assess any compensatory increase in the use of non-opioid illicit substances and alcohol in opioid dependent patients randomized to treatment with extended-release naltrexone or buprenorphine-naloxone (BP-NLX) and in longer term treatment with extended release naltrexone.Method: A 12-week, multicenter, outpatient, open-label randomized clinical trial and a subsequent 36-week follow-up study was conducted at five urban addiction clinics and detoxification units in Norway between November 1, 2012 and July 6, 2016. Opioid-dependent patients, n=143, aged 18-60 years who received at least one dose of study medication and who had at least one valid assessment after randomization were included in this study.The patients received intramuscular extended-release naltrexone hydrochloride, 380 mg/month, or daily sublingual buprenorphine-naloxone 8-24/2-6 mg for 12 weeks, and an option to continue with extended-release naltrexone for an additional 36 week follow-up period. Relapse rates were compared with Cox regression presented with hazard ratios (HR) with confidence intervals.Results: Among the 143 patients, 106 men and 37 women, there were no significant differences between those randomized to XR-NTX or BP-NLX in the risk of first relapse to alcohol (HR 1.31; 0.68-2.53), amphetamines (HR 0.88; 0.43-1.80), benzodiazepines (HR 1.24; 0.74-2.09) or cannabis (HR 1.55; 0.83-2.89). In the 36-week follow-up period we found no significant differences between patients continuing with XR-NTX and those switching to XR-NTX after the randomized period in risk of first relapse to alcohol (HR 0.97; 0.52-1.79), amphetamines (HR 0.82; 0.41-1.64), benzodiazepines (HR 1.28; 0.72-2.28), or cannabis (HR 1.35; 0.72-2.51). The substance use patterns were similar between the groups in both treatment periods except for a higher use of benzodiazepines in the BP-NLX group compared to XR-NTX (p<0.05). In both study periods, those relapsing to non-opioid addictive substances stayed longer in treatment than those who did not and there was no significant association between first relapse to illicit opioids and first relapse to non-opioid addictive substances.Conclusion: We found no increase in the risk of relapse to non-opioid addictive substances neither in short term nor longer term treatment with extended release naltrexone.

Aim: To investigate the association of adverse childhood experiences (ACEs) and substance use disorders (alcohol and illicit drug use disorders), specifically by gender, in a large longitudinal non-clinical population study. Methods: Data from 8199 adolescents, first assessed for ACE (2006-2008), were linked with subsequent data from the Norwegian Patient Register to obtain diagnoses of a substance use disorder in adulthood (after 12-14 years' follow-up in March 2020). This study used logistic regression analysis to assess the associations between ACEs and substance use disorders with respect to gender. Results: Adults with any history of ACEs have a 4.3-fold higher likelihood of developing a substance use disorder. Female adults had a 5.9-fold higher likelihood of developing an alcohol use disorder. Emotional neglect, sexual abuse and physical abuse were the strongest individual ACE predictors for this association. Male adults had a 5.0fold higher likelihood of developing an illicit drug use disorder (for example stimulants such as cocaine, inhibiter such as opioids, cannabinoids and multiple drugs). Physical abuse, parental divorce and witnessed violence were the strongest individual ACE predictors for this association. Conclusions: This study reinforces the association between ACEs and substance use disorders and exposes a gender-specific pattern. Increased attention should be paid to the meaning of individual ACEs as well as to the accumulation of ACEs in the development of a substance use disorder.