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The opioid epidemic is an ongoing public health crisis, and the United States health system is overwhelmed with increasing numbers of opioid-related overdoses. Methocinnamox (MCAM) is a novel mu opioid receptor antagonist with an extended duration of action. MCAM has potential to reduce the burden of the opioid epidemic by being used as an overdose rescue treatment and a long-term treatment for opioid use disorder (OUD). The currently available treatments for OUD include naloxone, naltrexone, and methadone. These treatments have certain limitations, which include short duration of action, patient non-compliance, and diversion. A narrative review was conducted using PubMed and Google Scholar databases covering the history of the opioid epidemic, pain receptors, current OUD treatments and the novel drug MCAM. MCAM could potentially be used as both a rescue and long-term treatment for opioid misuse. This is due to its pseudo-irreversible antagonism of the mu opioid receptor, abnormally long duration of action of nearly two weeks, and the possibility of using kappa or delta opioid receptor agonists for pain management during OUD treatment. MCAM’s novel pharmacokinetic and pharmacodynamic properties open a new avenue for treating opioid misuse.

BackgroundPast research has identified pronounced regional disparities in use of different opioids but less is known for codeine. The primary objective of this study was to analyze the trends of distribution of prescriptions containing codeine in the United States (US) from 2010 to 2019. In addition, this study aimed to identify regional disparities in prescribed milligrams of codeine per person in 2019 and identify any unusual states.MethodsThe distribution of codeine via pharmacies, hospitals, and practitioners in kilograms was obtained from the Drug Enforcement Administration’s Automated Reports and Consolidated Ordering System (ARCOS) from 2010 to 2019. In addition, the number of prescriptions of codeine per 1,000 Medicaid enrollees was obtained from the State Drug Utilization Database.ResultsThe total grams of codeine decreased (−25.0%) through all distributors from 2010 to 2019. The largest increase in total grams of codeine distributed between two consecutive years (2014 to 2015) was +28.9%. For a given distributor type, the largest decrease from 2010 to 2019 was hospitals (−89.6%). In 2019, the total mg of codeine per person distributed in Texas (11.46) was significantly higher relative to the national average (3.06, 1.88 SD). Codeine prescriptions to Medicaid patients peeked in the third quarter of 2016.ConclusionThe peak of prescription codeine in 2011 was consistent with the overall peak in prescription opioids, with a subsequent decrease over the decade. This could be explained by relatively recent recommendations regarding the therapeutic use of codeine and how other antitussive agents may be of better use. The precipitous rise of codeine in Texas that we observed has been recognized in prior studies. These state-level disparities warrant further attention by opioid stewardship committees.

BackgroundThe United States (US) is in the middle of an opioid overdose epidemic that has spanned over two decades and continues to escalate. Methadone is long-acting full opioid agonist which has been approved to treat opioid use disorder (OUD). Methadone can cause respiratory depression that may result in mortality. The restrictions on methadone availability including take-home dosing were loosened during the COVID-19 pandemic although there have been concerns about the high street value of diverted methadone. This report examined how fatal overdoses involving methadone have changed over the past two-decades including during the pandemic.MethodsThe Center for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (WONDER) database, which draws data from death certificates, was used to find the unintentional methadone related overdose death rate from 1999-2020. Unintentional methadone deaths were defined using the International Statistical Classification of Diseases (ICD), 10th revision codes: X40-44 with only data which was coded for methadone (T40.3). Data from the Automation of Reports and Consolidated Orders System (ARCOS) on methadone overall use, narcotic treatment programs use, and pain management use was gathered for all states, including the District of Columbia, for 2020 and corrected for population.ResultsThere have been dynamic changes over the past two-decades in overdoses involving methadone. Overdoses increased from 1999 (0.9/million) to 2007 (15.9) and declined until 2019 (6.5). Overdoses in 2020 (9.6) were 48.1% higher than in 2019 (t(50) = 3.05, p < .005).The correlations between overall methadone use (r(49) = +0.75, p < 0.001), and narcotic treatment program use (r(49) = +0.77, p < 0.001) were positive, strong, and statistically significant. However, methadone use for pain treatment was not associated with overdoses (r(49) = -.08, p = .57).ConclusionsOverdoses involving methadone significantly increased by 48.1% in 2020 relative to 2019. This mortality increase is much larger than the 5.3% elevation in calls involving methadone reported to poison control centers in the year following the March 16, 2020 loosening of methadone take-home regulations. Policy changes that were implemented following the COVID-19 pandemic involving methadone may warrant reconsideration.

Objectives: To identify US prescription trends in methadone distribution for OUD from 2010 to 2020. Methods: The weight of methadone in grams distributed to OTPs per state was derived from the US Drug Enforcement Administration's Automated Reports and Consolidated Ordering System. Methadone was adjusted for state population and compared across all fifty states and Washington DC from 2010 to 2020. Results: The overall distribution of methadone to OTPs significantly (P < 0.0001) increased from 2010 to 2019 (+61.0%) and from 2015 to 2020 (+26.22%). The states with the highest percent change from 2010 to 2020 were Montana (+897.02%), Alaska (+421.11%), and Vermont (+353.67%). In contrast with prior increase of distribution, from 2019 (pre-COVID-19 pandemic) to 2020 (during pandemic), there was no significant change in the distribution of methadone to OTPs (-0.09%). Ohio (+26.02%) significantly increased while Alabama (-21.96%), New Hampshire (-24.13%) and Florida (-28.97%) significantly decreased methadone relative to the national mean. Conclusions: This investigation revealed two trends related to methadone distribution in the US: increased utilization over the past decade and a plateau in utilization from 2019 to 2020. Policies are needed to remove access barriers to methadone treatment during the COVID-19 pandemic in order to reduce the worsening crisis of opioid overdoses in the US.