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BACKGROUND: Despite the widespread availability of naloxone, US opioid overdose rates continue to rise. The "Cascade of Care" (CoC) is a public health approach that identifies steps in achieving specific outcomes and has been used to identify gaps in naloxone carriage among individuals with opioid use disorder (OUD). We sought to apply this framework to a treatment-seeking population with OUD that may be more inclined to engage in harm reduction behaviors. METHODS: Patients were recruited from an urban methadone program to complete a survey. We assessed naloxone familiarity, availability, obtainability, training, and possession, as well as naloxone carriage rates, demographics, and harm reduction behaviors. A multivariable logistic regression examined associations between naloxone carriage and individual-level factors. RESULTS: Participants (n = 97) were majority male (59%), with a mean age of 48 (SD = 12), 27% had college education or higher, 64% indicated injection drug use, and 84% reported past naloxone training. All participants endorsed familiarity with naloxone, but only 42% regularly carried naloxone. The following variables were associated with carrying naloxone: White race (aOR = 2.94, 95% CI 1.02-8.52), college education (aOR = 8.11, 95% CI 1.76-37.47), and total number of self-reported harm reduction behaviors (aOR = 1.45, 95% CI 1.00-2.11). CONCLUSION: We found low rates of naloxone carriage among methadone-treated patients. Methadone programs provide opportunities for naloxone interventions and should target racial/ethnic minorities and individuals with lower education. The spectrum of harm reduction behaviors should be encouraged among these populations to enhance naloxone carriage.
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Sobredosis de Droga , Trastornos Relacionados con Opioides , Humanos , Masculino , Persona de Mediana Edad , Naloxona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Reducción del Daño , Sobredosis de Droga/tratamiento farmacológico , Trastornos Relacionados con Opioides/rehabilitación , Metadona/uso terapéutico , Analgésicos Opioides/uso terapéuticoRESUMEN
Rates of opioid use disorder (OUD) have increased dramatically over the past two decades, a rise that has been accompanied by changing demographics of those affected. Early exposure to drugs is a known risk factor for later development of opioid use disorder; but how and whether this risk factor may differ between racial groups is unknown. Our study seeks to identify race differences in self-report of current and past substance use in OUD-diagnosed treatment-seeking individuals. Patients (n = 157) presenting for methadone maintenance treatment at a racially diverse urban opioid treatment program were approached and consented for study involvement. Participants were administered substance use history questionnaires and urine drug screening at intake. Chi-square, t-tests, and rank-sum were used to assess race differences in demographic variables. Logistic and linear regressions assessed the relationship between race and substance use for binary and continuous variables, respectively. 61% of the population identified as Black and 39% as White. Black participants were significantly older; age was thus included as a covariate. Logistic regressions demonstrated that despite similar urine toxicology at intake, White participants were significantly more likely to report having used prescription opioids and psychedelic, stimulant, and sedative substance classes prior to their first use of non-pharmaceutical opioids. Compared to Black participants, White treatment-seeking OUD-diagnosed individuals reported using a wider range of substances ever and prior to first use of non-pharmaceutical opioids. There were no differences, however, in presentation for OUD treatment, suggesting different pathways to OUD, which may carry important clinical implications.
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Trastornos Relacionados con Opioides , Humanos , Trastornos Relacionados con Opioides/epidemiología , Metadona , Analgésicos Opioides/uso terapéutico , Tratamiento de Sustitución de Opiáceos , Grupos RacialesRESUMEN
This report builds on a previous study that describes the collaboration between an urban academic medical center and a rural drug treatment center, the goal of which is to provide medication-based treatment to individuals with OUD via videoconferencing. We describe results of a retrospective chart review of 472 patients treated in the program between August 2015 and April 2019. We examined several demographic and substance use variables for individuals who consented to telemedicine treatment, retention in treatment over time, and opioid use over time to understand further the impact of prescribing buprenorphine and naltrexone via telemedicine to patients in a rural OUD treatment setting. Our findings support the effectiveness of prescribing medications via telemedicine. The inclusion of more than three times as many patients as in our prior report revealed retention rates and toxicology results that are comparable to face-to-face treatment. These findings have implications for policymakers and clinicians considering implementation of similar programs.
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BACKGROUND: Patients' perceptions and experiences of stigma related to substance use and methadone treatment are barriers to successful treatment of opioid use disorder, particularly among low-income and medically underserved populations. Interventions led by peer recovery specialists (PRSs) may shift stigma-related barriers. This study sought to evaluate shifts in substance use and methadone treatment stigma in the context of an evidence-based behavioral intervention adapted for PRS delivery to support methadone treatment outcomes. METHODS: We recruited patients who had recently started methadone treatment or demonstrated difficulty with adherence from a community-based program (N = 37) for an open-label pilot study of a 12-session behavioral activation intervention led by a PRS interventionist. Participants completed substance use and methadone treatment stigma assessments and the SIP-R, a brief measure of problems related to substance use, at baseline, mid-point (approximately six weeks), and post-treatment (approximately 12 weeks). Generalized estimating equations assessed change in total stigma scores between baseline and post-treatment as well as change in stigma scores associated with change in SIP-R responses. RESULTS: There was a statistically significant decrease in substance use stigma (b(SE)=-0.0304 (0.0149); p = 0.042) from baseline to post-treatment, but not methadone treatment stigma (b(SE)=-0.00531 (0.0131); p = 0.68). Decreases in both substance use stigma (b(SE)=0.5564 (0.0842); p < 0.001) and methadone treatment stigma (b(SE)=0.3744 (0.1098); p < 0.001) were associated with a decrease in SIP-R scores. CONCLUSIONS: PRS-led interventions have potential to shift substance use stigma, which may be associated with decrease in problems related to substance use, and therefore merit further testing in the context of randomized controlled trials.
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Metadona , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides , Grupo Paritario , Estigma Social , Humanos , Masculino , Femenino , Metadona/administración & dosificación , Metadona/uso terapéutico , Adulto , Trastornos Relacionados con Opioides/rehabilitación , Proyectos Piloto , Persona de Mediana Edad , Terapia Conductista/métodos , Trastornos Relacionados con Sustancias/rehabilitación , Resultado del TratamientoRESUMEN
INTRODUCTION: Following the March 2020 federal declaration of a COVID-19 public health emergency, in line with recommendations for social distancing and decreased congregation, federal agencies issued sweeping regulation changes to facilitate access to medications for opioid use disorder (MOUD) treatment. These changes allowed patients new to treatment to receive multiple days of take-home medications (THM) and to use remote technology for treatment encounters-allowances that previously had been reserved exclusively for "stable" patients who met minimum adherence and time-in-treatment criteria. The impact of these changes on low-income, minoritized patients (frequently the largest recipients of opioid treatment program [OTP]-based addiction care), however, is not well characterized. We aimed to explore the experiences of patients who were enrolled in treatment prior to COVID-19 OTP regulation changes, with the goal of understanding patients' perceptions of the impact of these changes on treatment. METHODS: This study included semistructured, qualitative interviews with 28 patients. We used a purposeful sampling method to recruit individuals who were active in treatment just before COVID-19-related policy changes went into effect, and who were still in treatment several months later. To ensure a diverse array of perspectives, we interviewed individuals who either had or had not experienced challenges with methadone medication adherence from 3/24/21 to 6/8/21, approximately 12-15 months following the onset of COVID-19. Interviews were transcribed and coded using thematic analysis. RESULTS: Participants were majority male (57 %), Black/African American (57 %), with a mean age of 50.1 (SD = 9.3). Fifty percent received THM prior to COVID-19, which increased to 93 % during the pandemic. COVID-19 program changes had mixed effects on treatment and recovery experiences. Themes identified convenience, safety, and employment as reasons for preferring THM. Challenges included difficulty with managing/storing medications, experiencing isolation, and concern about relapse. Furthermore, some participants reported that telebehavioral health encounters felt less personal. CONCLUSIONS: Policymakers should consider patients' perspectives to foster a more patient-centered approach to methadone dosing that is safe, flexible, and accommodating to a diverse array of patients' needs. Additionally, technical support should be provided to OTPs to ensure interpersonal connections are maintained in the patient-provider relationship beyond the pandemic.
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COVID-19 , Trastornos Relacionados con Opioides , Humanos , Masculino , Persona de Mediana Edad , Analgésicos Opioides/uso terapéutico , Baltimore/epidemiología , Metadona/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Evaluación del Resultado de la Atención al PacienteRESUMEN
BACKGROUND: Despite efficacy of medication for opioid use disorder, low-income, ethno-racial minoritized populations often experience poor opioid use disorder treatment outcomes. Peer recovery specialists, individuals with lived experience of substance use and recovery, are well-positioned to engage hard-to-reach patients in treatment for opioid use disorder. Traditionally, peer recovery specialists have focused on bridging to care rather than delivering interventions. This study builds on research in other low-resource contexts that has explored peer delivery of evidence-based interventions, such as behavioral activation, to expand access to care. METHODS: We sought feedback on the feasibility and acceptability of a peer recovery specialist-delivered behavioral activation intervention supporting retention in methadone treatment by increasing positive reinforcement. We recruited patients and staff at a community-based methadone treatment center and peer recovery specialist working across Baltimore City, Maryland, USA. Semi-structured interviews and focus groups inquired about the feasibility and acceptability of behavioral activation, recommendations for adaptation, and acceptability of working with a peer alongside methadone treatment. RESULTS: Participants (N = 32) shared that peer recovery specialist-delivered behavioral activation could be feasible and acceptable with adaptations. They described common challenges associated with unstructured time, for which behavioral activation could be particularly relevant. Participants provided examples of how a peer-delivered intervention could fit well in the context of methadone treatment, emphasizing the importance of flexibility and specific peer qualities. CONCLUSIONS: Improving medication for opioid use disorder outcomes is a national priority that must be met with cost-effective, sustainable strategies to support individuals in treatment. Findings will guide adaptation of a peer recovery specialist-delivered behavioral activation intervention to improve methadone treatment retention for underserved, ethno-racial minoritized individuals living with opioid use disorder.
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Terapia Conductista , Trastornos Relacionados con Opioides , Humanos , Grupos Focales , Metadona/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológicoRESUMEN
INTRODUCTION: Successful engagement with medication treatment for opioid use disorder is an important focus in reducing mortality associated with the opioid crisis. Mortality remains at unacceptably high levels, pointing to a need for improved understanding of factors that affect medication for opioid use disorder outcomes. This study aims to understand how barriers co-occur and interact to interfere with outcomes in methadone treatment for a low-income, underserved patient population with opioid use disorder. METHODS: This study was conducted at a community-based drug treatment center that serves a predominately low-income, racially diverse population. Guided by the social-ecological framework, we analyzed semi-structured interviews and focus groups with patients and providers working in opioid use disorder care and recovery across Baltimore City (N = 32) to assess factors that influence methadone treatment outcomes, and how barriers co-occur and interact to worsen treatment outcomes. The study used patient-centered definitions to describe successful treatment outcomes. RESULTS: Barriers described by both patients and providers fit into several broad levels: individual, interpersonal, institutional, community, and stigma. Participants described co-occurrence of many barriers. Further, the study identified potential interactive effects, such that interrelated barriers were seen as fueling one another and having a deleterious effect on treatment outcomes. Specifically, interrelationships between barriers were described for 1) unstable housing with social influences and mental health factors; 2) transportation with poor physical health and other competing responsibilities; 3) treatment program policies and schedule with competing responsibilities; and 4) stigma with poor physical and mental health. CONCLUSIONS: Understanding barriers to successful medication for opioid use disorder outcomes and considering their co-occurrence may help to identify and promote interventions to mitigate their impact. This work is intended to guide future research to adapt conceptual frameworks for understanding psychosocial and structural barriers affecting opioid use disorder treatment and ultimately intervention efforts to improve treatment outcomes.
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Trastornos Relacionados con Opioides , Poblaciones Vulnerables , Humanos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Metadona/uso terapéutico , Pobreza , Grupos FocalesRESUMEN
Importance: Methadone treatment is the most effective evidence-based treatment for opioid use disorder (OUD), but challenges related to dosing and premature treatment dropout argue for adjunct interventions to improve outcomes. One potential behavioral intervention with low risk involves harnessing placebo effects. Objective: To determine the effect of a pharmacologically conditioned open-label placebo (C-OLP) on 90-day methadone dose, retention, drug use, withdrawal, craving, quality of life, and sleep. Design, Setting, and Participants: This 2-arm, open-label, single-blind randomized clinical trial was conducted between December 5, 2017, and August 2, 2019, in an academically affiliated community opioid treatment program. Analyses were conducted between October 1, 2019, and April 30, 2020. A total of 320 newly enrolled adults seeking treatment for moderate to severe OUD were assessed for study eligibility; 131 met eligibility criteria, provided informed consent, and were randomized to either C-OLP or treatment as usual (TAU) in an unequal-block (3:2) manner. Exclusion criteria were pregnancy, hospital/program transfers, and court-ordered treatment. Interventions: Participants randomized to C-OLP received pharmacologic conditioning and a placebo pill and methadone, and participants randomized to TAU were given methadone only. Participants met with the study team 5 times: at baseline (treatment intake) and 2, 4, 8, and 12 weeks postbaseline. Interactions were balanced between the 2 groups. Main Outcomes and Measures: Outcomes included 90-day methadone dose (primary) and treatment retention, drug use, withdrawal, craving, quality of life, and sleep quality (secondary). Analyses were conducted as intention-to-treat. Results: Of the 131 people enrolled in the study, 54 were randomized to TAU and 77 to C-OLP. Mean (SD) age was 45.9 (11.2) years; most of the participants were Black or African American (83 [63.4%]) and male (84 [64.1%]). No significant group differences were observed in the mean (SD) 90-day methadone dose (83.1 [25.1] mg for group TAU, 79.4 [19.6] mg for group C-OLP; t = 0.621991; P = .43), but the groups differed significantly in their retention rates: 33 (61.1%) for TAU and 60 (77.9%) for C-OLP (χ21 = 4.356; P = .04; number needed to treat for the beneficial outcome of 3-month treatment retention, 6; 95% CI, 4-119). C-OLP participants also reported significantly better sleep quality. Conclusions and Relevance: In this randomized clinical trial, C-OLP had no effect on the primary outcome of 90-day methadone dose. However, C-OLP participants were significantly more likely to remain in treatment. These findings support the use of C-OLP as a methadone treatment adjunct, but larger trials are needed to further examine the use of C-OLP. Trial Registration: ClinicalTrials.gov Identifier: NCT02941809.
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Metadona , Trastornos Relacionados con Opioides , Adulto , Masculino , Humanos , Persona de Mediana Edad , Metadona/uso terapéutico , Calidad de Vida , Método Simple Ciego , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/rehabilitación , Analgésicos Opioides/uso terapéuticoRESUMEN
Background and aims: There is growing evidence that psilocybin, a serotonergic psychedelic substance, may be useful in the treatment of substance use disorders. However, there is a lack of data on the beliefs and attitudes towards psilocybin amongst Black individuals diagnosed with Opioid Use Disorder (OUD). This study characterized psilocybin use patterns and perception of risk amongst a cohort of Black individuals diagnosed with OUD. Methods: Using a convenience sampling approach, patients were recruited from an urban methadone treatment program and paid five dollars to complete an anonymous phone-based survey. Results: Twenty-eight patients participated (mean age 53.8; N = 28; 35.7% female). Most (N = 23; 82.1%) had "heard of" psilocybin mushrooms before taking the survey, but only five (N = 5; 17.8%) had ever used them. More than 80% perceived a risk or were "unsure" of the risk for sixteen of the seventeen items queried about psilocybin. Approximately half (N = 15; 53.6%) were willing to try therapy incorporating psilocybin and half (N = 14; 50%) said they would be more likely to try if it were FDA approved for OUD. Most (N = 18; 64.3%) preferred to stay on methadone treatment alone, 32.1% (N = 9) wanted to try treatment with both psilocybin and methadone, and only one participant opted for psilocybin treatment without methadone. Conclusion: Many Black individuals with Opioid Use Disorder perceive psilocybin as dangerous and may be hesitant to try psilocybin treatment. Culturally informed treatment models, educational interventions and community outreach programs should be developed to increase racial/ethnic minority representation in psilocybin research and treatment.
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BACKGROUND: Despite the efficacy of methadone to treat opioid use disorder (OUD), retention is an urgent priority, particularly among low-income, minoritized populations. Peer recovery specialists are well-positioned to engage vulnerable patients, particularly when trained in an evidence-based intervention to promote retention. This hybrid effectiveness-implementation pilot trial aimed to demonstrate the proof of concept of a peer recovery specialist-delivered behavioral activation and problem solving-based approach (Peer Activate) to improve methadone retention. METHODS: Implementation outcomes included feasibility, acceptability, and fidelity. Feasibility and acceptability were defined by the percentage of participants who initiated the intervention (≥75%) and completed ≥75% of core sessions, respectively. Fidelity was assessed via independent rating of a randomly selected 20% of sessions. The primary effectiveness outcome was methadone retention at three-months post-intervention vs. a comparison cohort initiating methadone during the same time period. Secondary outcomes included methadone adherence, substance use frequency, and substance use-related problems. RESULTS: Benchmarks for feasibility and acceptability were surpassed: 86.5% (32/37) initiated the intervention, and 81.3% of participants who initiated attended ≥75% of core sessions. The mean independent rater fidelity score was 87.9%, indicating high peer fidelity. For effectiveness outcomes, 88.6% of participants in Peer Activate were retained in methadone treatment at three-months post-intervention-28.9% higher than individuals initiating methadone treatment alone in the same time period [χ2(1) = 10.10, p = 0.001]. Among Peer Activate participants, urine-verified methadone adherence reached 97% at post-intervention, and there was a significant reduction in substance use frequency from 48% of past two-week days used at baseline to 31.9% at post-intervention [t(25) = 1.82, p = .041]. Among participants who completed the core Peer Activate sessions (n = 26), there was a significant reduction in substance use-related problems [t(21) = 1.84, p = 0.040]. CONCLUSION: Given the rapid scale-up of peer recovery specialist programs nationwide and the urgent need to promote methadone retention, these results, although preliminary, have important potential clinical significance. The next steps are to conduct a Type 1 hybrid effectiveness-implementation randomized trial with a larger sample size and longer-term follow-up to further establish the implementation and effectiveness of the Peer Activate approach.
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Metadona , Trastornos Relacionados con Opioides , Terapia Conductista , Humanos , Metadona/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Proyectos Piloto , PobrezaRESUMEN
Purpose: Patients with opioid use disorder (OUD) face high rates of unemployment, putting them at higher risk of treatment nonadherence and poor outcomes, including overdose death. The objective of this study was to investigate sleep quality and its association with other biopsychosocial risk factors for unemployment in patients receiving opioid agonist treatment (OAT) for OUD. Methods: Using a cross-sectional survey design, participants from 3 OAT programs for OUD completed questionnaires to measure sleep quality (Pittsburgh Sleep Quality Index [PSQI]); pain disability; catastrophic thinking; injustice experience; quality of life; and self-assessed disability. Spearman's rank correlation was used to test for associations between sleep quality and other study variables. Results: Thirty-eight participants completed the study, with mean age 45.6 ± 10.9 years,â¯27 (71.1%) males, andâ¯16 (42.1%) reporting a high school diploma/equivalent certification as the highest level of academic attainment. Poor sleep quality (defined as PSQI > 5) was identified in 29 participants (76.3%) and was positively correlated with pain disability (r = 0.657, P < .01), self-assessed disability (r = 0.640, P < .001), symptom catastrophizing (r = 0.499, P < .001), and injustice experience (r = 0.642, P < .001), and negatively correlated with quality of life (r = -0.623, P < .001). Conclusions: There was a high prevalence of poor sleep quality in patients with OUD on OAT and this was associated with multiple known risk factors for unemployment. These findings warrant the consideration of regular screening for sleep problems and the inclusion of sleep-related interventions to improve sleep quality, decrease the unemployment rate, and enhance the recovery process for individuals with OUD undergoing OAT.
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Telemedicine is increasingly being used to treat patients with opioid use disorder (OUD). It has particular value in rural areas of the United States impacted by the opioid crisis as these areas have a shortage of trained addiction medicine providers. Patient satisfaction significantly impacts positive clinical outcomes in OUD treatment and thus is of great clinical interest. Yet little is known regarding patient satisfaction with the increasingly important platform of telemedicine-delivered medications for opioid use disorder (tMOUD). The goal of this review is to provide a summary of the existing literature regarding patient satisfaction with tMOUD. We also submit a novel survey based on an existing framework designed to assess tMOUD satisfaction, and present pilot data (N = 14) acquired from patients engaged in rural tMOUD care. Telemedicine provides a feasible method for delivering MOUD in rural areas, and our survey provides a useful assessment to measure patient satisfaction with tMOUD. In light of the pressing need for innovative and technology-driven solutions to the opioid epidemic (especially in light of the COVID-19 pandemic), future research should focus on the development and refinement of tools to assess the important implementation goal of patient satisfaction.
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Buprenorfina/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Satisfacción del Paciente , Telemedicina , Adulto , Humanos , Tratamiento de Sustitución de Opiáceos , Epidemia de Opioides , Población Rural , Encuestas y Cuestionarios , Estados UnidosRESUMEN
INTRODUCTION: More than 2 million individuals in the USA have an opioid use disorder (OUD). Methadone maintenance treatment is the gold standard of medication-based treatment for OUD, but high-dose methadone is associated with cardiotoxicity and respiratory complications, among other side effects. These adverse effects make enhancing the effectiveness of lower doses of methadone an attractive therapeutic goal. Long recognised for its capacity to enhance treatment outcomes for a wide range of neuropsychiatric disorders including pain, the placebo effect offers an as-yet untested avenue to such an enhancement. This approach is particularly compelling given that individuals with substance use disorder tend to have higher salience attribution and may thereby be more sensitive to placebo effects. Our study combines two promising clinical methodologies-conditioning/dose-extension and open-label placebo-to investigate whether placebo effects can increase the effective potency of methadone in treatment-seeking OUD patients. METHODS AND ANALYSIS: A total of 120 newly enrolled treatment-seeking OUD patients will be randomly assigned to one of two different groups: either methadone plus daily placebo dose-extension (PDE; treatment group) or methadone/treatment as usual (control). Participants will meet with study team members five times over the course of 3 months of treatment with methadone (baseline, 2 weeks, and 1, 2 and 3 months postbaseline). Throughout this study time period, methadone dosages will be adjusted by an addiction clinician blind to patient assignment, per standard clinical methods. The primary outcome is methadone dose at 3 months. Secondary outcomes include self-report of drug use; 3-month urine toxicology screen results; and treatment retention. Exploratory outcomes include several environmental as well as personality factors associated with OUD and with propensity to demonstrate a placebo effect. ETHICS AND DISSEMINATION: Human subjects oversight for this study is provided by the University of Maryland, Baltimore and University of Maryland, College Park Institutional Review Boards. Additionally, the study protocol is reviewed annually by an independent Data and Safety Monitoring Board. Study results will be disseminated via research conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT02941809.
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Metadona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Tratamiento de Sustitución de Opiáceos/métodos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Adulto , Prescripciones de Medicamentos , Femenino , Humanos , Masculino , Maryland/epidemiología , Metadona/farmacología , Antagonistas de Narcóticos/farmacología , Trastornos Relacionados con Opioides/epidemiología , Proyectos Piloto , Placebos/uso terapéutico , Prueba de Estudio Conceptual , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Identifying non-addictive opioid medications is a high priority in medical sciences, but µ-opioid receptors mediate both the analgesic and addictive effects of opioids. We found a significant pharmacodynamic difference between morphine and methadone that is determined entirely by heteromerization of µ-opioid receptors with galanin Gal1 receptors, rendering a profound decrease in the potency of methadone. This was explained by methadone's weaker proficiency to activate the dopaminergic system as compared to morphine and predicted a dissociation of therapeutic versus euphoric effects of methadone, which was corroborated by a significantly lower incidence of self-report of "high" in methadone-maintained patients. These results suggest that µ-opioid-Gal1 receptor heteromers mediate the dopaminergic effects of opioids that may lead to a lower addictive liability of opioids with selective low potency for the µ-opioid-Gal1 receptor heteromer, exemplified by methadone.