BACKGROUND:The US opioid overdose epidemic continues to escalate. 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. METHODS:The CDC's Wide-ranging Online Data for Epidemiologic Research (WONDER) was used to find the unintentional methadone related overdose death rate from 1999 to 2020. Unintentional methadone deaths were defined using the ICD X40-44 codes with only data for methadone (T40.3). Data from the DEA's Automation of Reports and Consolidated Orders System (ARCOS) on methadone overall use, opioid treatment programs use, and pain management use was gathered for all states for 2020 and corrected for population. RESULTS:There have been dynamic changes over the past two-decades in methadone overdoses. 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 state level correlations between overall methadone use (r(49) = +0.75, p < .001), and opioid treatment program use (r(49) = +0.77, p < .001) with overdoses were positive, strong, and statistically significant. However, methadone use for pain treatment was not associated with methadone overdoses (r(49) = -0.08). CONCLUSIONS:Overdoses involving methadone significantly increased by 48.1% in 2020 relative to 2019. Policy changes that were implemented following the COVID-19 pandemic involving methadone take-homes may warrant further study before they are made permanent.

Objective: Some individuals with attention-deficit/hyperactivity disorder (ADHD) may not tolerate or adequately respond to currently available treatments. This study examined whether solriamfetol could have a favorable pattern of effects and tolerability as a treatment for ADHD in adults.Methods: Sixty adults with DSM-5 ADHD participated from August 2021 through January 2023 in a remotely conducted, randomized, double-blind, placebo-controlled, 6-week dose -optimization trial of 75 mg or 150 mg of solriamfetol. Measures included the Adult ADHD Investigator Symptom Rating Scale (AISRS), which was our primary outcome measure, as well as the Clinical Global Impressions scale (CGI), vital signs, the Global Assessment of Functioning (GAF), the Behavior Rating Inventory of Executive Function-Adult Form (BRIEF-A), the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), and a modified Adult ADHD Self-Report Scale (MASRS). Results: Solriamfetol was well tolerated, with no significant effect on mean heart rate (+3.7 vs +2.2 bpm, P=.5609), systolic blood pressure (+2.4 vs +1.5 mm Hg, P=.6474), or diastolic blood pressure (+1.1 vs +1.5 mm Hg, P=.8117). There was no statistically significant treatment effect on occurrence of adverse events. Compared to individuals on placebo, individuals on solriamfetol treatment experienced adverse events at a rate of at least 10 percentage points higher in the categories of decreased appetite, headache, gastrointestinal, insomnia, increased energy, cardiovascular, and neurologic. Compared to individuals on placebo, by study endpoint, a greater proportion of individuals in the treatment group met the a priori -defined treatment response (CGI score indicating much or very much improved and AISRS score reduced >= 25%: 45% vs 6.9%, P=.0020); those treated with solriamfetol also had greater improvement in total AISRS scores by week 3 through week 6 (P=.0012; week 6 effect size=1.09). Significantly more solriamfetoltreated adults than placebo-treated adults had 0.5-standard deviation improvement in T-score on the BRIEF-A Global Executive Composite (P=.0173); those treated with solriamfetol also had greater mean change in GAF score (-4.8 vs-0.3, P=.0006) and greater mean MASRS total score change (P=.0047; effect size=1.23). Mean ESS score improved more with solriamfetol than with placebo (P=.0056), but this difference did not predict AISRS response (P=.3735). There was no significant association between solriamfetol and change in PSQI scores.Conclusions: Solriamfetol may be a novel and effective treatment for the management of ADHD in adults. Further replication in larger trials is indicated.Trial Registration: ClinicalTrials.gov identifier: NCT04839562

Objective: Validate the usability and treatment-sensitivity of a remote SMS-based ADHD monitoring method. Method: 206 adults taking stimulants for ADHD participated. Participants selected ADHD symptoms and functional impairments that they anticipated to be stimulant-sensitive, which were rated via mobile messages up to 20 times over 10 days. Results: A majority of participants found it only somewhat or not at all difficult to identify an ADHD symptom sensitive to presence of stimulant medication, and 79% responded to at least one survey message. As expected, a majority of participants endorsed it was “easy” to participate, and less burdensome than a paper diary. Surveys significantly discriminated between on and off medication states, both between days, and within the same day. Conclusion: Our findings suggest SMS-based monitoring of patient-selected ADHD-related challenges is both feasible and sensitive to stimulant treatment. This remote assay method may be a meaningful adjunct to in-visit treatment monitoring

The United States is enduring a preventable opioid crisis, particularly involving a population being treated in a hospital setting, a subset of whom may escalate to illicit opioids. This project analyzed trends in distribution of opioids by hospitals in the United States. Opioids monitored included buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, powdered opium, remifentanil, and tapentadol. The Automation of Reports and Consolidated Orders System (ARCOS) reports on substances controlled by the Drug Enforcement Administration. National data from ARCOS reports 5 and 7 from 2000 to 2019 were used for an observational study on hospital opioid distribution. Morphine milligram equivalents (MMEs) were calculated using oral conversion factors. The MME per person per state was calculated to compare data from the peak year, 2012, with data from 2019. Opioid use peaked in 2012, with a -46.6% decline from 2012 to 2019. Half (25) of the states have seen a decrease of -50% or greater. Of the opioid compounds observed, buprenorphine has seen increased (+122.5%) hospital use from 2012 to 2019. All other opioids have been experiencing a decline (>= 50%), particularly hydromorphone (-49.9%), oxymorphone (-57.7%), methadone (-58.7%), morphine (-66.9%), codeine (-67.5%), and meperidine (-77.6%). There was a 6-fold difference in population-corrected use of opioids in 2019 between the lowest (6.8 MME/person in New Jersey) and highest (Alaska = 39.6) states. This study demonstrates the considerable progress made thus far by hospitals in curbing the U.S. opioid crisis.

Background: The 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. Methods: The Center for Disease Control and Preventions 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. Results: There 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). Conclusions: Overdoses 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.

Introduction The US opioid overdose epidemic has risen to an all-time high. Prescription opioids often serve as a gateway to illicit opioids, which have appreciable overdose potential. Recent investigations have highlighted the efficacy and safety of cannabis-based products for pain management. Providing alternative pain treatment options may help mitigate the opioid epidemic. Methods The distribution of codeine, fentanyl, hydrocodone, morphine, and oxycodone per 100 000 people and by 3-digit zip codes from 2014 to 2018 in California and Texas were compared. Overdose rates were also evaluated. California legalized recreational marijuana in 2016, but in Texas marijuana is functionally prohibited. Drug weights were obtained from the Automation of Reports and Consolidated Orders System and converted to oral morphine milligram equivalents. Overdose data was retrieved from the Centers for Disease Control’s WONDER database. Results California and Texas showed significant reductions in cumulative opioid distribution from 2014 to 2018 (− 43.7% and − 27.3%, respectively). Opioid distribution per 100 000 people decreased − 38.9% in California relative to − 26.4% in Texas. Opioid and heroin overdoses increased between 1999 and 2019 by + 11.6% in California but + 272.7% in Texas. Discussion This evidence supports marijuana legalization as a mitigating factor to the opioid epidemic and opioid misuse.

ABSTRACTThe United States is enduring a preventable opioid crisis, particularly involving a population specifically being treated in a hospital setting. This project analyzed trends in distribution of opioids by hospitals in the United States from 2000 to 2019. Opioids monitored included buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, powdered opium, remifentanil, and tapentadol. The Automation of Reports and Consolidated Orders System (ARCOS) reports controlled substances via the Drug Enforcement Administration (DEA). Data from ARCOS reports 5 and 7 from 2000 to 2019 were utilized for an observational study on hospital opioid distribution in the US. Morphine milligram equivalents (MME) were calculated using oral conversion factors for each opioid. The MME per person per state was calculated to compare data from the peak year, 2012, to data from 2019. Opioid use in the United States peaked in 2012 with a 46.6% decline from 2012 to 2019. Within the US, 25 of 50 states have seen a decrease of 50% or greater. Of the opioid compounds observed, buprenorphine has seen increased (123%) hospital use from 2000 to 2019. All other opioids have been experiencing a slow decline (>40%) in hospital use since that time. This study demonstrated the progress made thus far by hospitals in curbing the US opioid epidemic.

ABSTRACTIntroductionThe Diversion Alert Program (DAP) was established to curb the misuse of drugs and help identify people in need of substance use disorder (SUD) treatment. Law enforcement compiled arrest data into a database accessible by health care providers. The objectives of this investigation were to identify regional and demographic differences in drug use and misuse in Maine.MethodsAll arrests (N = 11,234) reported to the DAP from 2013 to 2018 were examined by county, arrestee demographics, and classified into families (opioids, stimulants, sedatives). The Automation of Reports and Consolidated Orders System (ARCOS) tracks the distribution of controlled pharmaceuticals (schedule I-V). Opioids were converted to oral morphine mg equivalents (MME). County and zip-code heat maps were constructed.ResultsThe counties with the most arrests per capita were Cumberland, Androscoggin, and Penobscot. Opioids were the most common drug class in arrests in all counties except Aroostook, where stimulants were most common. Medical distribution of opioids varied. With the exception of buprenorphine, which doubled, many prescription opioids like hydrocodone, fentanyl, and oxymorphone exhibited large (>50%) reductions. Methadone was the predominant opioid statewide (56.4% of the total MME) although there were sizeable differences (Presque Isle = 8.6%, Bangor = 78.9%) and this is likely impacted by use for SUD treatment. Amphetamine distribution increased by 67.9%. Conclusions: The DAP was useful to prevent information silos and enhance communication between law enforcement and health care providers. Maine’s DAP was a unique system to identify patients in need of additional treatment resources. The increase in prescription stimulants may warrant continued monitoring.

Abstract Introduction The United States is in the midst of an opioid overdose epidemic. Emerging evidence suggests that medical cannabis (MC) may reduce use of opioids for pain in some individuals, with potential impacts on opioid-related overdose. However, there may be other important differences between states that did, and did not, adopt MC. Methods This study evaluated differences following legal MC sales on US opioid-related overdose deaths, corrected for population, from 1999 to 2017 using an interrupted time series. Comparisons by MC status were also made for Medicaid expansion and the Centers for Disease Control death certificate reporting quality (0: <good, 1: good, 2: excellent). Results Overdose deaths were significantly higher in MC states from 2012–2017. Overdose death slopes over time increased in states with (pre=1.46±0.46, post=2.90±0.58, p<0.05) and without (pre =0.20±.10, post=1.04±0.22, p<0.005) MC. Post-legalization slopes were significantly higher in MC states (p<0.01). Two states without (11.1%) as compared to 11 states with (91.7%) MC expanded Medicaid by 2014 (χ2[1]=19.03, p<0.0005). MC states (1.50±0.23) had higher death certificate reporting quality relative to states without MC (0.78±0.22, p<0.05). Discussion MC states had higher rates of opioid overdoses. Although there was no decrease in association with MC introduction, these results were confounded by states without MC having lower overdose reporting quality. Medicaid expansion was also more common in states with MC. Finally, the potency of fentanyl analogues may have obscured any protective effects of MC against illicit opioid harms.

There have been dynamic changes in prescription opioid use in the US but the state level policy factors contributing to these are incompletely understood. We examined the association between the legalization of recreational marijuana and prescription opioid distribution in Colorado. Utah and Maryland, two states that had not legalized recreational marijuana, were selected for comparison. Prescription data reported to the Drug Enforcement Administration for nine opioids used for pain (e.g., fentanyl, morphine, hydrocodone, hydromorphone, oxycodone, oxymorphone) and two primarily for opioid use disorder (OUD, methadone and buprenorphine) from 2007 to 2017 were evaluated. Analysis of the interval pre (2007–2012) versus post (2013–2017) marijuana legalization revealed statistically significant decreases for Colorado (P < 0.05) and Maryland (P < 0.01), but not Utah, for pain medications. There was a larger reduction from 2012 to 2017 in Colorado (–31.5%) than the other states (–14.2% to –23.5%). Colorado had a significantly greater decrease in codeine and oxymorphone than the comparison states. The most prevalent opioids by morphine equivalents were oxycodone and methadone. Due to rapid and pronounced changes in prescription opioid distribution over the past decade, additional study with more states is needed to determine whether cannabis policy was associated with reductions in opioids used for chronic pain.

The United States is in the midst of an opioid overdose epidemic. A prior report using the Center for Disease Control’s Wide-ranging Online Data for Epidemiologic Research (WONDER) database discovered that opioid overdoses decreased by 24.8% from 1999 to 2010 in states with medical cannabis (MC+) relative to those without (MC−). The present study evaluated any differences following MC legislation on WONDER reported opioid overdoses, corrected for population, from 1999 to 2017 using an interrupted time series. Overdoses were significantly higher in MC+ states from 2012-2017. The slope of opioid overdose deaths over time increased significantly post-implementation in states without MC (3-years Pre = 0.1 ± 0.1, 3-years Post = 0.7 ± 0.2, (16) = 2.88, ≤ .011). Overdose deaths showed a non-significant elevation in states with MC (Pre = 1.3 ± 0.3, Post = 2.8 ± 0.8, (11) = 2.01, = .069). Post-legalization slopes were significantly higher in MC+ than MC− ((11.95) = 2.70, < .05). Overall, any impact of medical cannabis laws on opioid overdoses appears modest. There are other confounds (e.g. death determination reporting quality) which differ non-randomly among states and are non-trivial to account for in ecological investigations of cannabis policy. Alternatively, the potency of fentanyl analogues may obscure any protective effects of MC against illicit opioid harms.