The use of naltrexone in the treatment of chronic pain: a systematic review.

This study aims to assess the efficacy of low-dose naltrexone (LDN) in treating chronic pain. We conducted a systematic review using the PICO strategy: (P) Patients with chronic pain, (I) Use of oral naltrexone, (C) Placebo or active drug and (O) Pain relief and quality of life. We included articles from PubMed, Scopus, Cochrane CENTRAL and EMBASE databases. Seven randomized clinical trials involving 406 patients were analyzed. The doses ranging from 2 to 4.5 mg once daily across all studies. Various chronic pain conditions were evaluated. The results suggest that low-dose naltrexone is not effective in managing chronic pain and improving the quality of life in patients with diverse chronic pain conditions. However, further research with larger sample sizes and standardized methodologies is necessary.

This study looks at how well low-dose naltrexone (LDN) works for treating long-lasting pain. We reviewed research where patients with chronic pain were given either LDN or a placebo (a fake treatment). We found eight studies that included a total of 421 patients. The LDN doses used ranged from very small amounts 2­4.5 mg, taken once a day. These studies looked at different types of chronic pain. Our results suggest that LDN cannot help to reduce pain and improve the quality of life for people with chronic pain. However, more research with larger groups of people and consistent methods is needed to confirm these findings.

Narcanazo: Community Activation of Antiracist Epidemiology.

The Latinx (Hispanic) social construct obscures differences in the overdose risk levels of groups within this category. When national data are disaggregated, stateside Puerto Rican mortality increases exponentially, so much that this community has the highest rates of overdose deaths across years. Developed by Bronx-based Puerto Ricans, Narcanazo is an empowered upstander campaign that uses local overdose data to mobilize community members as trained naloxone dispensers. This health promotion campaign was grounded in antiracist epidemiological analysis. (Am J Public Health. 2024;114(S6):S463-S466. https://doi.org/10.2105/AJPH.2024.307605) [Formula: see text].

Sex differences in descending control of nociception (DCN) responses after chronic orofacial pain induction in rats and the contribution of kappa opioid receptors.

Descending control of nociception (DCN), a measure of efficiency of descending pain inhibition, can be assessed in animals by the combined application of test and conditioning noxious stimuli. Evidence from pre-clinical and clinical studies indicates that this mechanism of pain control may differ between sexes and might be impaired in many chronic pain states. However, little is known about sex differences in DCN efficiency in models of acute and chronic orofacial pain. Herein, we first evaluated DCN responses in male and female rats by the applying formalin into the upper lip or capsaicin into the forepaw as the conditioning stimulus, followed by mechanical stimulation (Randall-Selitto) of the hind paw as the test stimulus. The same protocol (i.e., capsaicin in the forepaw followed by mechanical stimulation of the hind paw) was evaluated in male and female rats on day 3 after intraoral incision and on day 15 and 30 after chronic constriction injury of the infraorbital nerve (CCI-ION). Additionally, we assessed the effect of the kappa opioid receptor (KOR) antagonist Norbinaltorphimine (nor-BNI) on DCN responses of female nerve-injured rats. This study shows that naïve female rats exhibit less efficient DCN compared to males. Postoperative pain did not alter DCN responses in female and male rats, but CCI-ION induced loss of DCN responses in females but not in males. Systemic pretreatment with nor-BNI prevented the loss of DCN induced by CCI-ION in female rats. The results reveal sex differences in DCN responses and female-specific impairment of DCN following chronic orofacial pain. Moreover, the findings suggest that, at least for females, blocking KOR could be a promising therapeutic approach to prevent maladaptive changes in chronic orofacial pain.

Designing and Evaluating COVID-19 Protocols for an Office-Based Opioid Treatment Program in an Urban Underserved Setting.

BACKGROUND: Despite changing federal regulations for providing telehealth services and provision of controlled substances during the COVID-19 pandemic, there is little guidance available for office-based opioid treatment (OBOT) programs integrated into primary care settings. PURPOSE: (1) Develop disaster-preparedness protocols specific to the COVID-19 pandemic for an urban OBOT program, and (2) evaluate the impacts of the protocol and telehealth on care. METHODS: Disaster-preparedness protocols specific to the COVID-19 pandemic were developed for an urban OBOT program, implemented on March 16, 2020. Retrospective chart review compared patients from January 1, 2020 to March 13, 2020, to patients from March 16, 2020 to April 30, 2020, abstracting patient demographics and comparing show and no-show rates between studied groups. RESULTS: The disaster-preparedness protocol was developed under a deliberative process to address social issues of the urban underserved population. Of 852 visits conducted between Jan 1, 2020, and April 30, 2020, a 91.7% show rate (n = 166/181) was documented for telemedicine visits after protocol implementation compared with a 74.1% show rate (n = 497/671) for routine in-person care (P = .06) without significant differences between the study populations. The no-show rate was significantly lower after protocol implementation (8.3% vs 25.9%; P <0.05). CONCLUSIONS: OBOTs require organized workflows to continue to provide services during the COVID-19 pandemic. Telemedicine, in the face of relaxed federal regulations, has the opportunity to enhance addiction care, creating a more convenient as well as an equally effective mechanism for OBOTs to deliver care that should inform future policy.

Low Doses Naltrexone: The Potential Benefit Effects for its Use in Patients with Cancer.

Naltrexone (NTX) is an opioid antagonist that inhibits cell proliferation in vivo when administered in low doses. Naltrexone in low doses can reduce tumor growth by interfering with cell signalling as well as by modifying the immune system. It acts as an Opioid Growth Factor receptor (OGFr) antagonist and the OGF-OGFr axis is an inhibitory biological pathway present in human cancer cells and tissues, being a target for the treatment with naltrexone low-dose (LDN). Clinical trials have proposed a unique mechanism(s) allowing LDN to affect tumors. LDN shows promising results for people with primary cancer of the bladder, breast, liver, lung, lymph nodes, colon and rectum. This short review provides further evidence to support the role of LDN as an anticancer agent.

Preparing pharmacists to increase naloxone dispensing within community pharmacies under the Pennsylvania standing order.

PURPOSE: Opioid misuse and overdose deaths remain a public health concern in the United States. Pennsylvania has one of the highest rates of opioid overdose deaths in the country, with Philadelphia County's being 3 times higher than the national average. Despite several multimodal interventions, including use of SBIRT (screening, brief intervention, and referral to treatment) methods and naloxone distribution, the rate of overdose deaths remains high. METHODS: To gain insights on strategies for improving access to naloxone and naloxone distribution by pharmacists in Philadelphia County, a study was conducted in 11 community pharmacies (chain and independent) in Philadelphia. Twenty-four pharmacists were recruited and completed SBIRT and naloxone trainings. Each pharmacy elected to have at least 1 pharmacy champion who received additional training on and helped develop pharmacy site-specific naloxone dispensing protocols. RESULTS: Pre-post survey results showed a reduction in stigmatizing attitudes regarding naloxone dispensing and an increase in pharmacists' understanding of the standing order and appropriate naloxone use. There was an increase in pharmacists' self-reported confidence in their ability to appropriately identify, discuss, and dispense naloxone to patients. All pharmacies increased their average monthly dispensing rate following protocol implementation. CONCLUSION: Pharmacists who received both trainings were more likely to change naloxone dispensing practices, leading to an overall increase in naloxone dispensing by community pharmacists. The study addressed overall gaps in pharmacists' knowledge, reduced stigma, and prepared pharmacists to address opioid use and overdose prevention with their patients. The described pharmacist-led patient counseling and intervention service for overdose prevention may be explored as a model for other community pharmacies to adopt to improve naloxone dispensing and similar interventions to reduce overdose deaths.

Socially distant and out of reach: Unintended consequences of COVID-19 prevention efforts on transgender and gender non-binary populations in Puerto Rico.

Substance use disorders in the United States disproportionately affect minorities and socially vulnerable populations, particularly those at the intersection of racial and sexual minority status. Preceded by over a century-long subjugation to the U.S. government, a recent financial crisis, the devastating hurricanes of 2017, and a string of earthquakes at the end of 2019 and early 2020, the current COVID-19 pandemic is only the most recent disaster to disrupt the local health care system in Puerto Rico. However, the effects of the current emergency and imposed social distancing measures have only exacerbated the underlying vulnerabilities of the transgender and gender non-conforming (GNC) population made bare during these other recent disasters. Clinics and providers who treat patients with opioid use disorder (OUD) in Puerto Rico have had to develop their own safety protocols to limit the spread of the virus while trying to optimize current treatment protocols to maintain the stability of their patients. Despite these measures, we have observed a reduction in the ability of local organizations to outreach to already disconnected transgender and GNC individuals with OUD. For example, due to the government-imposed curfew that began March 15, 2020, some providers engaged in outreach with transgender and GNC sex workers have eliminated nighttime outreach completely. Additionally, a research project surveying all buprenorphine prescribers in Puerto Rico has found that few have received training in treating this vulnerable population, and even fewer report that they are currently providing treatment for transgender or GNC individuals. If Puerto Rico is to address this problem of gross under-representation of a population known to be disproportionately affected by substance use disorders, Puerto Rico must address structural factors to prevent this disparity from widening further during the inevitable future disasters our health care system will face.

Barriers to and recommendations for take-home naloxone distribution: perspectives from opioid treatment programs in New Mexico.

BACKGROUND: Naloxone is a safe and effective medication to help reverse opioid overdose. Providing take-home naloxone to patients in opioid treatment settings is a critical step to reducing opioid overdose deaths. In New Mexico, a US state with one of the highest rates of opioid overdose deaths, legislation was passed in 2017 (House Bill 370) to support take-home naloxone, and followed by naloxone training of Opioid Treatment Program staff to increase distribution. METHODS: Naloxone training was offered to all New Mexico Opioid Treatment Programs along with a baseline survey to assess current practices and barriers to take-home naloxone distribution. Focus groups were conducted approximately 1 year post-training with staff at a subset of the trained Opioid Treatment Programs to assess the impact of the legislation and training provided. RESULTS: Baseline survey results show most Opioid Treatment Program staff were unfamiliar with House Bill 370, reported conflicting understandings of their agency's current take-home naloxone practices, and reported a number of barriers at the patient, agency, and policy level. Follow-up focus groups revealed support for House Bill 370 but persistent barriers to its implementation at the patient, agency, and policy level including patient receptivity, cost of naloxone, staff time, and prohibitive pharmacy board regulations. CONCLUSIONS: In spite of targeted legislation and training, provision of take-home naloxone at remained low. This is alarming given the need for this lifesaving medication among the Opioid Treatment Program patient population, and high opioid death rate in New Mexico. Locally, important next steps include clarifying regulatory guidelines and supporting policy/billing changes to offset costs to Opioid Treatment Programs. Globally, additional research is needed to identify the prevalence of take-home naloxone distribution in similar settings, common barriers, and best practices that can be shared to increase access to this vital lifesaving medication in this critical context.

Analysis of psychiatrists' prescription of opioid, benzodiazepine, and buprenorphine in Medicare Part D in the United States.

INTRODUCTION: The opioid epidemic is a severe problem in the world, especially in the United States, where prescription opioid overdose accounts for a quarter of drug overdose deaths. OBJECTIVE: To describe psychiatrists' prescription of opioid, benzodiazepine, and buprenorphine in the United States. METHODS: We conducted a retrospective cross-sectional study of the 2016 Medicare Part D claims data and analyzed psychiatrists' prescriptions of: 1) opioids; 2) benzodiazepines, whose concurrent prescription with opioids can cause overdose death; 3) buprenorphine, a partial opioid agonist for treating opioid addiction; 4) and naltrexone microsphere, a once-monthly injectable opioid antagonist to prevent relapse to opioid dependence. Prescribers with 11 or more claims were included in the analysis. RESULTS: In Medicare Part D in 2016, there were a total of 1,131,550 prescribers accounting for 1,480,972,766 total prescriptions and 78,145,305 opioid prescriptions, including 25,528 psychiatrists (2.6% of all prescribers) accounting for 44,684,504 total prescriptions (3.0% of all prescriptions) and 131,115 opioid prescriptions (0.2% of all opioid prescriptions). Psychiatrists accounted for 17.3% of benzodiazepine, 16.3% of buprenorphine, and 33.4% of naltrexone microsphere prescriptions. The opioid prescription rate of psychiatrists was much lower than that of all prescribers (0.3 vs 5.3%). The buprenorphine prescription rate of psychiatrists was much higher than that of all prescribers (2.3 vs. 0.1%). There was a substantial geographical variation across the United States. CONCLUSIONS: The results show that, proportionally, psychiatrists have lower rates of opioid prescription and higher rates of benzodiazepine and buprenorphine prescription.

Analysis of psychiatrists' prescription of opioid, benzodiazepine, and buprenorphine in Medicare Part D in the United States

Abstract Introduction The opioid epidemic is a severe problem in the world, especially in the United States, where prescription opioid overdose accounts for a quarter of drug overdose deaths. Objective To describe psychiatrists' prescription of opioid, benzodiazepine, and buprenorphine in the United States. Methods We conducted a retrospective cross-sectional study of the 2016 Medicare Part D claims data and analyzed psychiatrists' prescriptions of: 1) opioids; 2) benzodiazepines, whose concurrent prescription with opioids can cause overdose death; 3) buprenorphine, a partial opioid agonist for treating opioid addiction; 4) and naltrexone microsphere, a once-monthly injectable opioid antagonist to prevent relapse to opioid dependence. Prescribers with 11 or more claims were included in the analysis. Results In Medicare Part D in 2016, there were a total of 1,131,550 prescribers accounting for 1,480,972,766 total prescriptions and 78,145,305 opioid prescriptions, including 25,528 psychiatrists (2.6% of all prescribers) accounting for 44,684,504 total prescriptions (3.0% of all prescriptions) and 131,115 opioid prescriptions (0.2% of all opioid prescriptions). Psychiatrists accounted for 17.3% of benzodiazepine, 16.3% of buprenorphine, and 33.4% of naltrexone microsphere prescriptions. The opioid prescription rate of psychiatrists was much lower than that of all prescribers (0.3 vs 5.3%). The buprenorphine prescription rate of psychiatrists was much higher than that of all prescribers (2.3 vs. 0.1%). There was a substantial geographical variation across the United States. Conclusions The results show that, proportionally, psychiatrists have lower rates of opioid prescription and higher rates of benzodiazepine and buprenorphine prescription.

[Treatment of borderline personality disorder with opioid antagonists: buprenorphine, nalmefene, naloxone and naltrexone in the treatment of dissociative symptoms, self-mutilation and suicidal behavior]. / Tratamiento del Trastorno límite de la personalidad con antagonistas opioides: buprenorfina, nalmefeno, naloxona y naltrexona en el tratamiento de síntomas disociativos, automutilaciones y conducta suicida.

OBJECTIVE: Recent theory has proposed that a dysfunction of the opioid system modulates mood, reward and pain; seems to be unstable in people with Borderline Personality Disorder. Our purpose is to analyze the evidence on the efficacy of the use of buprenorphine, nalmefene, naloxone and naltrexone, in the treatment of dissociative symptoms, self-mutilation and suicidal behavior of these patients. METHOD: We conducted a systematic search of MEDLINE and LILACS databases, to retrieve relevant articles. Included studies were experimental and observational designs of borderline personality samples in which dissociative symptoms, self mutilation or suicidal behavior was reported as an outcome and evaluated with some impact measures. RESULTS: A total of eight studies were reviewed. These provided interesting expectations about posible treatment lines in Borderline Personality Disorder using opioid antagonists. The subgroup most benefited was the one who has analgesia and highest number of diagnostic criteria. CONCLUSIONS: Studies of higher methodological quality are needed, in larger population samples and using control of confounding variables that allow us to estimate a value power calculation, and thus be able to support firm conclusions.

Acute antinociceptive effect of fish oil or its major compounds, eicosapentaenoic and docosahexaenoic acids on diabetic neuropathic pain depends on opioid system activation.

Diabetic neuropathic pain is one of the most common and debilitating complications of diabetes whose available treatments are poorly effective. Currently, omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have been widely studied as a treatment of many types of pain, including inflammatory, spontaneous and neuropathic pain. However, little is known about the potential antinociceptive effect of ω-3 PUFAs (fish oil; FO or its major fatty acids, eicosapentaenoic -EPA and docosahexaenoic acids-DHA), in diabetic neuropathic pain as well as the mechanisms involved. To test, streptozotocin (STZ) -induced diabetic male Wistar rats were submitted to acute treatment with FO, EPA or DHA at the second and fourth weeks after diabetes induction (at the beginning and peak of development of mechanical allodynia, respectively). The cumulative effect of these compounds after a sub-chronic treatment for two weeks was also evaluated as well as the role of central µ-opioid receptors. It was observed that acute oral treatment with FO (0.5, 1 or 3 g/kg), EPA or DHA (100, 200 or 400 mg/kg) at the 2nd or at the 4th week after STZ significantly reverted the mechanical allodynia of diabetic animals, without altering the hyperglycemia or reduced weight gain. Moreover, the sub-chronic treatment with FO, EPA or DHA induced a sustained antinociceptive effect in diabetic animals. Intriguingly, the intrathecal treatment with a µ-opioid receptor antagonist (CTOP; 10 µg/rat) completely prevented the acute effect of FO, EPA or DHA. Taken together, our data suggest that ω-3 PUFAs may represent a promising therapeutic outcome for diabetic neuropathic pain, probably acting through the opioid system activation.

The Hypnotic, Anxiolytic, and Antinociceptive Profile of a Novel µ-Opioid Agonist.

5'-4-Alkyl/aryl-1H-1,2,3-triazole derivatives PILAB 1-12 were synthesized and a pharmacological screening of these derivatives was performed to identify a possible effect on the Central Nervous System (CNS) and to explore the associated mechanisms of action. The mice received a peritoneal injection (100 µmol/kg) of each of the 12 PILAB derivatives 10 min prior to the injection of pentobarbital and the mean hypnosis times were recorded. The mean hypnosis time increased for the mice treated with PILAB 8, which was prevented when mice were administered CTOP, a µ-opioid antagonist. Locomotor and motor activities were not affected by PILAB 8. The anxiolytic effect of PILAB 8 was evaluated next in an elevated-plus maze apparatus. PILAB 8 and midazolam increased a percentage of entries and spent time in the open arms of the apparatus compared with the control group. Conversely, a decrease in the percentages of entries and time spent in the closed arms were observed. Pretreatment with naloxone, a non-specific opioid antagonist, prior to administration of PILAB 8 exhibited a reverted anxiolytic effect. PILAB 8 exhibited antinociceptive activity in the hot plate test, and reduced reactivity to formalin in the neurogenic and the inflammatory phases. These data suggest that PILAB 8 can activate µ-opioid receptors to provoke antinociceptive and anti-inflammatory effects in mice.

Men Who Have Sex With Men in Peru: Acceptability of Medication-Assisted Therapy for Treating Alcohol Use Disorders.

In Peru, the HIV epidemic is concentrated in men who have sex with men (MSM) and transgender women (TGW). Multiple studies correlate alcohol use disorders (AUDs) with risky sexual behaviors among Peruvian MSM. Qualitative research was used to inform a clinical trial on the acceptability of medication-assisted therapies to assist management of AUDs and improve antiretroviral therapy (ART) adherence among MSM/TGW in Peru. Three focus groups involving HIV-infected or HIV-uninfected MSM/TGW ( n = 26) with AUDs (AUDIT ≥ 8) were transcribed, translated from Spanish into English, and analyzed using thematic content analysis. Despite having an AUD, participants considered themselves "social" drinkers, minimized their drinking behaviors, and differed about whether or not alcohol problems could be treated. Participants expressed skepticism about medication for treating AUDs. Three concepts emerged as necessary components of a treatment program for alcohol problems: cost, family support, and the potential to drink less alcohol without attaining total abstinence. This study reveals important areas of education to increase potential acceptability of a medication for treating AUDs among MSM/TGW. Given the social conditions and knowledge base of the participants, medication-assisted therapies using naltrexone may be a beneficial strategy for MSM with AUDs.

Recognition and response to opioid overdose deaths-New Mexico, 2012.

PURPOSE: Drug overdose deaths are epidemic in the U.S. Prescription opioid pain relievers (OPR) and heroin account for the majority of drug overdoses. Preventing death after an opioid overdose by naloxone administration requires the rapid identification of the overdose by witnesses. This study used a state medical examiner database to characterize fatal overdoses, evaluate witness-reported signs of overdose, and identify opportunities for intervention. METHODS: We reviewed all unintentional drug overdose deaths that occurred in New Mexico during 2012. Data were abstracted from medical examiner records at the New Mexico Office of the Medical Investigator. We compared mutually exclusive groups of OPR and heroin-related deaths. RESULTS: Of the 489 overdose deaths reviewed, 49.3% involved OPR, 21.7% involved heroin, 4.7% involved a mixture of OPR and heroin, and 24.3% involved only non-opioid substances. The majority of OPR-related deaths occurred in non-Hispanic whites (57.3%), men (58.5%), persons aged 40-59 years (55.2%), and those with chronic medical conditions (89.2%). Most overdose deaths occurred in the home (68.7%) and in the presence of bystanders (67.7%). OPR and heroin deaths did not differ with respect to paramedic dispatch and CPR delivery, however, heroin overdoses received naloxone twice as often (20.8% heroin vs. 10.0% OPR; p<0.01). CONCLUSION: OPR overdose deaths differed by age, health status, and the presence of bystanders, yet received naloxone less often when compared to heroin overdose deaths. These findings suggest that naloxone education and distribution should be targeted in future prevention efforts.

Baclofen prevents the elevated plus maze behavior and BDNF expression during naloxone precipitated morphine withdrawal in male and female mice.

In previous studies we have shown that baclofen, a selective GABAB receptor agonist, prevents the somatic expression and reestablishes the dopamine and µ-opioid receptors levels, modified during naloxone-precipitated morphine withdrawal syndrome in male and female mice. There are no previous reports regarding sex differences in the elevated plus maze (EPM) and the expression of BDNF in morphine-withdrawn mice. The present study analyses the behavioral and biochemical variations during morphine withdrawal in mice of both sexes, and whether these variations are prevented with baclofen. Swiss-Webster albino prepubertal mice received morphine (2 mg/kg, i.p.) twice daily, for 9 consecutive days. On the 10th day, one group of morphine-treated mice received naloxone (opioid receptor antagonist; 6 mg/kg, i.p.) 1 h after the last dose of morphine to precipitate withdrawal. A second group received baclofen (2 mg/kg, i.p.) before naloxone administration. The EPM behavior was measured during 15 min after naloxone injection. The expression of BDNF-positive cells was determined by immunohistochemistry. Withdrawn male mice showed a higher percentage of time spent and number of entries to the open arms compared to withdrawn female mice. Baclofen prevented this behavior in both sexes. BDNF expression decreased in the AcbC, BNST, CeC, and CA3 of the hippocampus while increased in the BLA of morphine withdrawn male. Baclofen pretreatment prevented the BDNF expression observed in morphine withdrawn male mice in all the brain areas studied except in the CeC. Baclofen prevention of the EPM behavior associated to morphine withdrawal could be partially related to changes in BDNF expression.

Opioid antagonists in broadly defined behavioral addictions: a narrative review.

INTRODUCTION: Naltrexone (NTX), a mu-opioid receptor antagonist, has been approved for the treatment of alcoholism and opioid dependence. More recently, however, NTX and a related drug, nalmefene (NMF), have also shown positive results for the treatment of gambling disorders. AREAS COVERED: In this study, we reviewed the trials testing the effect of opioid antagonists (OA) in gambling disorders and in other broadly defined behavioral addictions, including selected DSM-5 disruptive, impulse-control, and conduct disorders, obsessive-compulsive and related disorders, eating disorders, and other conditions not currently recognized by official classification schemes. We found six randomized controlled trials (RCTs) of OA in gambling disorder, two RCTs of OA in trichotillomania (hair pulling disorder), two RCTs of OA in binge eating disorder, and one RCT of OA for kleptomania. We also reviewed case reports on hypersexual disorder, compulsive buying and skin picking disorders. EXPERT OPINION: The reviewed data supported the use of OA, namely NTX and NMF, in gambling disorder (both) and kleptomania (NTX). We did not find enough evidence to support the use of NTX or NMF in trichotillomania (hair pulling disorder), excoriation (skin-picking) disorder, compulsive buying disorder, hypersexual disorder, or binge eating disorder.

American Society of Addiction Medicine (ASAM) National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use.

The Centers for Disease Control have recently described opioid use and resultant deaths as an epidemic. At this point in time, treating this disease well with medication requires skill and time that are not generally available to primary care doctors in most practice models. Suboptimal treatment has likely contributed to expansion of the epidemic and concerns for unethical practices. At the same time, access to competent treatment is profoundly restricted because few physicians are willing and able to provide it. This "Practice Guideline" was developed to assist in the evaluation and treatment of opioid use disorder, and in the hope that, using this tool, more physicians will be able to provide effective treatment. Although there are existing guidelines for the treatment of opioid use disorder, none have included all of the medications used at present for its treatment. Moreover, few of the existing guidelines address the needs of special populations such as pregnant women, individuals with co-occurring psychiatric disorders, individuals with pain, adolescents, or individuals involved in the criminal justice system. This Practice Guideline was developed using the RAND Corporation (RAND)/University of California, Los Angeles (UCLA) Appropriateness Method (RAM) - a process that combines scientific evidence and clinical knowledge to determine the appropriateness of a set of clinical procedures. The RAM is a deliberate approach encompassing review of existing guidelines, literature reviews, appropriateness ratings, necessity reviews, and document development. For this project, American Society of Addiction Medicine selected an independent committee to oversee guideline development and to assist in writing. American Society of Addiction Medicine's Quality Improvement Council oversaw the selection process for the independent development committee. Recommendations included in the guideline encompass a broad range of topics, starting with the initial evaluation of the patient, the selection of medications, the use of all the approved medications for opioid use disorder, combining psychosocial treatment with medications, the treatment of special populations, and the use of naloxone for the treatment of opioid overdose. Topics needing further research were noted.