Ketamine and hydroxynorketamine as novel pharmacotherapies for the treatment of Opioid-Use Disorders.

Opioid use disorder (OUD) has reached epidemic proportions, with many countries facing high opioid use and related fatalities. Although currently-prescribed medications for OUD (MOUD) are considered life-saving, they inadequately address negative affect and cognitive impairment, resulting in high relapse rates to non-medical opioid use, even years after drug cessation (protracted abstinence). Evidence supports the notion that ketamine, an anesthetic and rapid-acting antidepressant drug, holds promise as a candidate for OUD treatment, including the management of acute withdrawal somatic symptoms, negative affect during protracted opioid abstinence and prevention of re-taking non-medical opioids. In this review, we comprehensively discuss preclinical and clinical research evaluating ketamine and its metabolites as potential novel therapeutic strategies for treating OUDs. We further examine evidence supporting the relevance of the molecular targets of ketamine and its metabolites in relation to their potential effects and therapeutic outcomes in OUDs. Overall, existing evidence demonstrates that ketamine and its metabolites can effectively modulate pathophysiological processes affected in OUD, suggesting their promising therapeutic role in the treatment of OUD and the prevention of return to opioid use during abstinence.

Perspectives of physicians and doulas on shared decision-making and decision counseling in the treatment of pregnant women with opioid use disorders.

INTRODUCTION: Research about the application of shared decision-making (SDM) in the context of Medication Assisted Treatment (MAT) for pregnant women with opioid use disorder (OUD) is limited. The objectives of our study were to 1) examine facilitators of and barriers to SDM for the initiation of MAT in clinical practice and 2) evaluate the receptivity of clinicians and doulas involved in the care of women with OUD to the use of an online software application to facilitate SDM about MAT. METHODS: This qualitative study utilized semi-structured interviews with consenting physicians and doulas who provided care for pregnant women with OUD between November 2021 and May 2022. Participants were asked about factors influencing SDM in practice. In addition, the study asked participants about the feasibility of using the Jefferson Decision Counseling Guide© (JDCG) to educate pregnant women with OUD as to the benefits and risks of undergoing MAT versus no treatment and to help patients clarify their treatment preference. The study recorded the interview and transcribed it verbatim using Rev. transcription services. The study used thematic analyses to code the data and identify key barriers and facilitators of SDM and perceptions of the SDM tool. RESULTS: Nineteen participants completed interviews. The study identified several barriers to SDM including time constraints, lack of decision counseling tools at points of care, and patients presenting in an actively high state or withdrawing. Peer workers or other trained personnel, giving patients more time, and comfort in decision counseling are examples of facilitators identified by the participants of the study. Participants believed that the counseling tool could facilitate conversations with patients and should be integrated into the workflow. CONCLUSION: In this qualitative study, we identified several barriers and facilitators of SDM to initiate MAT for pregnant women with OUD. Our findings indicate that there are challenges and opportunities for healthcare systems to increase SDM in this marginalized patient population. Feedback from participants highlighted their receptivity to the use of SDM tools to facilitate meaningful conversations in various settings that can guide decision making about care.

Implementation of medication for opioid use disorder treatment during a natural disaster: The PROUD-LA study.

BACKGROUND: The impacts of climate change-related extreme weather events (EWEs) on Medication for Opioid Use Disorders (MOUD) implementation for Medicaid beneficiaries are relatively unknown. Such information is critical to disaster planning and other implementation strategies. In this study we examined implementation determinants and strategies for MOUD during EWEs. METHODS: The Louisiana-based Community Resilience Learning Collaborative and Research Network (C-LEARN) utilized Rapid Assessment Procedures-Informed Community Ethnography (RAPICE), involving community leaders in study design, execution, and data analysis. We conducted qualitative semi-structured interviews with 42 individuals, including MOUD Medicaid member patients and their caregivers, healthcare providers and administrators, and public health officials with experience with climate-related disasters. We mapped key themes onto updated Consolidated Framework for Implementation Research domains. RESULTS: MOUD use is limited during EWEs by pharmacy closures, challenges to medication prescription and access across state lines, hospital and clinic service limits, overcrowded emergency departments, and disrupted communications with providers. MOUD demand simultaneously increases due to the stress associated with displacement, resource loss, the COVID-19 pandemic, and social determinants of health. Effective implementation strategies include healthcare system disaster plans with protocols for clear and regular patient-provider communication, community outreach, additional staffing, and virtual delivery of services. Providers can also increase MOUD access by having remote access to EHRs, laptops and contact information, resource lists, collaborative networks, and contact with patients via call centers and social media. Patients can retain access to MOUD via online patient portals, health apps, call centers, and provider calls and texts. The impact of EWEs on MOUD access and use is also influenced by individual characteristics of both patients and providers. CONCLUSIONS: The increasing frequency and severity of climate-related EWEs poses a serious threat to MOUD for Medicaid beneficiaries. MOUD-specific disaster planning and use of telehealth for maintaining contact and providing care are effective strategies for MOUD implementation during EWEs. Potential considerations for policies and practices of Medicaid, providers, and others to benefit members during hurricanes or major community stressors, include changes in Medicaid policies to enable access to MOUD by interstate evacuees, improvement of medication refill flexibilities, and incentivization of telehealth services for more systematic use.

The effects of buprenorphine and morphine during pregnancy: Impact of exposure length on maternal brain, behavior, and offspring neurodevelopment.

The escalating incidence of opioid-related issues among pregnant women in the United States underscores the critical necessity to understand the effects of opioid use and Medication for Opioid Use Disorders (MOUDs) during pregnancy. This research employed a translational rodent model to examine the impact of gestational exposure to buprenorphine (BUP) or morphine on maternal behaviors and offspring well-being. Female rats received BUP or morphine before conception, representing established use, with exposure continuing until postnatal day 2 or discontinued on gestational day 19 to mimic treatment cessation before birth. Maternal behaviors - including care, pup retrieval, and preference - as well as hunting behaviors and brain neurotransmitter levels were assessed. Offspring were evaluated for mortality, weight, length, milk bands, surface righting latency, withdrawal symptoms, and brain neurotransmitter levels. Our results reveal that regardless of exposure length (i.e., continued or discontinued), BUP resulted in reduced maternal care in contrast to morphine-exposed and control dams. Opioid exposure altered brain monoamine levels in the dams and offspring, and was associated with increased neonatal mortality, reduced offspring weight, and elevated withdrawal symptoms compared to controls. These findings underscore BUP's potential disruption of maternal care, contributing to increased pup mortality and altered neurodevelopmental outcomes in the offspring. This study calls for more comprehensive research into prenatal BUP exposure effects on the maternal brain and infant development with the aim to mitigate adverse outcomes in humans exposed to opioids during pregnancy.

Development of an Educational Brochure about Treatment Options for Pregnant Women with Opioid Use Disorders.

The goal of this study was to describe the development of an educational brochure for pregnant women with opioid use disorders (OUDs) about treatment options. Based on findings from a preliminary review of the literature, we drafted a brochure that addressed the following questions: (1) What are your options (Medication-Assisted Treatment (MAT) versus no treatment)? (2) What are the benefits of MAT? (3) What are the risks of MAT? (4) Can I take buprenorphine or methadone while breastfeeding? (5) Which medication should I choose? Clinicians and doulas (n = 19) who provide care to pregnant women with OUDs were recruited. Semi-structured interviews elicited participants' feedback on brochure content and their perceptions about brochure use for patient education. Thematic data analyses were performed. Three emergent themes were identified (suggested uses and settings of use, content revisions, and perceptions about the brochure) and used to refine the final brochure. This study provides valuable insights into the desired content of an educational brochure describing treatment options for pregnant women with OUDs from the provider's standpoint. Research is needed to assess the use of the brochure in shared decision-making conversations with providers about treatment.

[Appropriate use of strong opioids in medical units: Recommendations and action to be taken in daily practice]. / Bon usage des opioïdes forts dans les unités de médecine : état des lieux des recommandations et conduite à tenir en pratique quotidienne.

The use of strong opioids in medical units is recurrent, mainly for analgesic purposes. The risk of occurrence of an overdose or an opioid use disorders causes very legitimate concerns for the physician, which may limit the use of opioid treatment or the adaptation of the doses necessary to relieve the patient. We provide a summary of the literature aimed at defining the indications, the adverse effects and the risks involved, the prescribing methods in order to reassure professionals and promote the safe use of these molecules.

Provider perspectives on the impact of COVID-19 on treatment of substance use and opioid use disorders among American Indian and Alaska Native adults.

Introduction: American Indian/Alaska Native (AI/AN) communities are more likely to suffer negative consequences related to substance misuse. The COVID-19 pandemic exacerbated the opioid poisoning crisis, in combination with ongoing treatment barriers resulting from settler-colonialism, systemic oppression and racial discrimination. AI/AN adults are at greatest risk of COVID-19 related serious illness and death. In collaboration with an Indigenous community advisory board and Tribal leadership, this study explored AI/AN treatment provider perceptions of client-relatives' (i.e., SUD treatment recipients) experiences during the pandemic from 2020 to 2022. Methods: Providers who underwent screening and were eligible to participate (N = 25) represented 6 programs and organizations serving rural and urban areas in Washington, Utah, and Minnesota. Participants engaged in audio-recorded 60-90 min semi-structured individual interviews conducted virtually via Zoom. The interview guide included 15 questions covering regulatory changes, guidance for telemedicine, policy and procedures, staff communication, and client-relatives' reactions to implemented changes, service utilization, changes in treatment modality, and perceptions of impact on their roles and practice. Interview recordings were transcribed and de-identified. Members of the research team independently reviewed transcripts before reaching consensus. Coding was completed in Dedoose, followed by analyses informed by a qualitative descriptive approach. Results: Five main domains were identified related to client-relative experiences during the COVID-19 pandemic, as observed by providers: (1) accessibility, (2) co-occurring mental health, (3) social determinants of health, (4) substance use, coping, and harm reduction strategies, and (5) community strengths. Providers reported the distinctive experiences of AI/AN communities, highlighting the impact on client-relatives, who faced challenges such as reduced income, heightened grief and loss, and elevated rates of substance use and opioid-related poisonings. Community and culturally informed programming promoting resilience and healing are outlined. Conclusion: Findings underscore the impact on SUD among AI/AN communities during the COVID-19 pandemic. Identifying treatment barriers and mental health impacts on client-relatives during a global pandemic can inform ongoing and future culturally responsive SUD prevention and treatment strategies. Elevating collective voice to strengthen Indigenous informed systems of care to address the gap in culturally-and community-based services, can bolster holistic approaches and long-term service needs to promote SUD prevention efforts beyond emergency response efforts.

Cognitive behaviour therapy as an evidence-based intervention for opioid use disorder: A systematic review.

Objective: To explore the effectiveness of cognitive behaviour therapy as an evidence-based intervention for patients with opioid use disorder and to estimate the effect of cognitive behaviour therapy in mental health care settings. METHODS: The systematic review was conducted from January to April 2023, and comprised search on Web of Science, PsycINFO, Medline, Embase, Google Scholar, Science Direct, PubMed, ClinicalTrials and OvidSP databases for experimental studies and randomised controlled trials related to opioid use disorders published in peer-reviewed English-language journals between December 2022 and April 2023. The studies' quality was assessed using the Modified Cochrane Collaboration risk of the bias assessment criteria. RESULTS: Of the 314 studies initially identified, 42(13%) were subjected to full-text assessment, and 10(23.8%) were analysed. There were 5(50%) studies done in the United States, 2(20%) in Iran, and 1(10%) each in Germany, China and England. All 10(100%) studies were randomised controlled trials with intervention-based cognitive behaviour therapy, and reported significant results in patients diagnosed with opioid use disorders. Conclusion: All the studies analysed were heterogeneous. Cognitive behaviour therapy had a short-term impact and remained influential in the long term as well in handling cognitive and behaviour setbacks among patients with opioid use disorders.

Contextualizing medications for opioid use disorder and peer support service provision in the probation system with implementation science.

BACKGROUND: Medications for opioid use disorder (MOUD) is an evidence-based approach that reduces opioid-related mortality, particularly among criminal legal-involved persons who are at increased risk of adverse outcomes related to OUD. Implementing evidence-based approaches in the context of probation settings requires an in-depth understanding of specific contexts to improve intervention efficacy and effectiveness. Here, we use the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework to understand implementation contexts for MOUD provision in the probation setting. METHODS: In-depth individual interviews were conducted with key programmatic stakeholders (treatment providers and probation staff involved in service provision for people on probation). The study examined stakeholder perspectives regarding MOUD and Peer Support Service (PSS) implementation among people who are involved in community supervision. Deductive and inductive thematic analysis was conducted, and subsequently the codes, subcodes, and themes were mapped onto the EPIS framework to better understand implementation contexts. RESULTS: We deduced key inner, outer, and bridging contexts that shape treatment service provision for individuals with OUD who are on probation. Inner contexts include a strong organizational climate that supports MOUD implementation and enthusiasm for peer support services. Outer contexts include difficulty navigating insurance among providers, treatment costs, and systemic stigma towards MOUD. Bridging contexts include a lack of collaboration/communication between relevant agencies (e.g., probation and courts). CONCLUSIONS: Findings indicate the implementation is complex and requires a coordinated effort between correctional systems, probation agencies, and community-based treatment providers.

Effects of a Two-Month Exercise Training Program on Concurrent Non-Opiate Substance Use in Opioid-Dependent Patients during Substitution Treatment.

BACKGROUND: This randomized controlled trial aimed to evaluate the effects of a two-month exercise intervention on the concurrent non-opiate substance use (alcohol, cocaine, cannabis, and benzodiazepines) in opioid users during their medication treatment. METHODS: Ninety opioid users (41 females) in methadone and buprenorphine medication treatment were randomly divided into four groups: (a) buprenorphine experimental (BEX; n = 26, aged 41.9 ± 6.1 yrs); (b) buprenorphine control (BCON; n = 25, aged 41.9 ± 5.6 yrs); (c) methadone experimental (MEX; n = 20, aged 46.7 ± 6.6 yrs); and (d) methadone control (MCON; n = 19, aged 46.1 ± 7.5 yrs). The experimental groups (BEX and MEX) followed an aerobic exercise training program on a treadmill for 20 min at 70% HRmax, 3 days/week for 8 weeks. Socio-demographic, anthropometric, and clinical characteristics, as well as non-opioid drug use in days and quantity per week, were assessed before and after the intervention period. RESULTS: Following the exercise training, the weekly non-opioid substance consumption (days) decreased (p < 0.05) in both exercise groups and was lower in BEX compared to MEX, while no differences were observed (p > 0.05) between the control groups (BCON vs. MCON) or compared to their baseline levels. Similarly, the daily amount of non-opiate substance intake was reduced (p < 0.05) post-training in BEX and MEX, whereas it did not differ (p > 0.05) in BCON and MCON compared to the baseline. CONCLUSIONS: The two-month exercise intervention reduced the non-opioid drug use in both the methadone and buprenorphine substitution groups compared to the controls, suggesting that aerobic exercise training may be an effective strategy for treating patients with OUDs.