Retrospective study investigating naloxone prescribing and cost in US Medicaid and Medicare patients.

BACKGROUND: Opioid overdoses in the USA have increased to unprecedented levels. Administration of the opioid antagonist naloxone can prevent overdoses. OBJECTIVE: This study was conducted to reveal the pharmacoepidemiologic patterns in naloxone prescribing to Medicaid patients from 2018 to 2021 as well as Medicare in 2019. DESIGN: Observational pharmacoepidemiologic study SETTING: US Medicare and Medicaid naloxone claims INTERVENTION: The Medicaid State Drug Utilisation Data File was utilised to extract information on the number of prescriptions and the amount prescribed of naloxone at a national and state level. The Medicare Provider Utilisation and Payment was also utilised to analyse prescription data from 2019. OUTCOME MEASURES: States with naloxone prescription rates that were outliers of quartile analysis were noted. RESULTS: The number of generic naloxone prescriptions per 100 000 Medicaid enrollees decreased by 5.3%, whereas brand naloxone prescriptions increased by 245.1% from 2018 to 2021. There was a 33.1-fold difference in prescriptions between the highest (New Mexico=1809.5) and lowest (South Dakota=54.6) states in 2019. Medicare saw a 30.4-fold difference in prescriptions between the highest (New Mexico) and lowest states (also South Dakota) after correcting per 100 000 enrollees. CONCLUSIONS: This pronounced increase in the number of naloxone prescriptions to Medicaid patients from 2018 to 2021 indicates a national response to this widespread public health emergency. Further research into the origins of the pronounced state-level disparities is warranted.

Immunotherapy and Cannabis: A Harmful Drug Interaction or Reefer Madness?

A retrospective (N = 140) and a prospective (N = 102) observational Israeli study by Bar-Sela and colleagues about cannabis potentially adversely impacting the response to immunotherapy have together been cited 202 times, including by clinical practice guidelines. There have also been concerns on PubPeer outlining irregularities and unverifiable information in their statistics and numerous errors in calculating percentages. This reanalysis attempted to verify the data analysis while including non-parametric statistics. The corrected prospective report contained 22 p-values, but only one (4.5%) could be verified despite the authors being transparent about the N and statistics employed. Cannabis users were significantly (p < 0.0025) younger than non-users, but this was not reported in the retrospective report. There were also errors in percentage calculations (e.g., 13/34 reported as 22.0% instead of 38.2%). Overall, these observational investigations, and especially the prospective, appear to contain gross inaccuracies which could impact the statistical decisions (i.e., significant findings reported as non-significant or vice-versa). Although it is mechanistically plausible that cannabis could have immunosuppressive effects which inhibit the response to immunotherapy, these two reports should be viewed cautiously. Larger prospective studies of this purported drug interaction that account for potential confounds (e.g., greater nicotine smoking among cannabis users) may be warranted.

Dispensaries and Medical Marijuana Certifications and Indications: Unveiling the Geographic Connections in Pennsylvania, USA.

Introduction: Pennsylvania opened its first medical marijuana (MMJ) dispensary in 2018. Qualifying conditions include six conditions determined to have no or insufficient evidence to support or refute MMJ effectiveness. We conducted a study to describe MMJ dispensary access in Pennsylvania and to determine whether dispensary proximity was associated with MMJ certifications and community demographics. Methods: Using data from the Pennsylvania Department of Health, we geocoded MMJ dispensary locations and linked them to US Census Bureau data. We created dispensary access measures from the population-weighted centroid of Zip Code Tabulation Areas (ZCTAs): distance to nearest dispensary and density of dispensaries within a 15-min drive. We evaluated associations between dispensary access and the proportion of adults who received MMJ certification and the proportion of certifications for low evidence conditions (amyotrophic lateral sclerosis, epilepsy, glaucoma, Huntington's disease, opioid use disorder, and Parkinson's disease) using negative binomial modeling, adjusting for community features. To evaluate associations racial and ethnic composition of communities and distance to nearest dispensary, we used logistic regression to estimate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for median income. Results: Distance and density of MMJ dispensaries were associated with the proportion of the ZCTA population certified and the proportion of certifications for insufficient evidence conditions. Compared to ZCTAs with no dispensary within 15 min, the proportion of adults certified increased by up to 31% and the proportion of certifications for insufficient evidence decreased by up to 22% for ZCTAs with two dispensaries. From 2018 to 2021, the odds of being within five miles of a dispensary was up to 20 times higher in ZCTAs with the highest proportions of individuals who were not White (2019: OR: 20.14, CI: 10.7-37.8) and more than double in ZCTAs with the highest proportion of Hispanic individuals (2018: OR: 2.81, CI: 1.51-5.24), compared to ZCTAs with the lowest proportions. Conclusions: Greater dispensary access was associated with the proportions of certified residents and certifications for low evidence conditions. Whether these patterns are due to differences in accessibility or demand is unknown. Associations between community demographics and dispensary proximity may indicate MMJ access differences.

Decreases and Pronounced Geographic Variability in Antibiotic Prescribing in Medicaid.

Antibiotic resistance is a persistent and growing concern. Our objective was to analyze antibiotic prescribing in the United States (US) in the Medical Expenditure Panel System (MEPS) and to Medicaid patients. We obtained MEPS prescriptions for eight antibiotics from 2013 to 2020. We extracted prescribing rates per 1000 Medicaid enrollees for two years, 2018 and 2019, for four broad-spectrum (azithromycin, ciprofloxacin, levofloxacin, and moxifloxacin) and four narrow-spectrum (amoxicillin, cephalexin, doxycycline, and trimethoprim-sulfamethoxazole) antibiotics. Antibiotic prescriptions in MEPS decreased from 2013 to 2020 by 38.7%, with a larger decline for the broad (-53.7%) than narrow (-23.5%) spectrum antibiotics. Antibiotic prescriptions in Medicaid decreased by 6.7%. Amoxicillin was the predominant antibiotic, followed by azithromycin, cephalexin, trimethoprim-sulfamethoxazole, doxycycline, ciprofloxacin, levofloxacin, and moxifloxacin. Substantial geographic variation in prescribing existed, with a 2.8-fold difference between the highest (Kentucky = 855/1000) and lowest (Oregon = 299) states. The South prescribed 52.2% more antibiotics (580/1000) than the West (381/1000). There were significant correlations across states (r = 0.81 for azithromycin and amoxicillin). This study identified sizable disparities by geography in the prescribing rates of eight antibiotics with over three-fold state-level differences. Areas with high prescribing rates, particularly for outpatients, may benefit from stewardship programs to reduce potentially unnecessary prescribing.

State-level variation in distribution of oxycodone and opioid-related deaths from 2000 to 2021: an ecological study of ARCOS and CDC WONDER data in the USA.

OBJECTIVES: This study aims to characterise oxycodone's distribution and opioid-related overdoses in the USA by state from 2000 to 2021. DESIGN: This is an observational study. SETTING: More than 80 000 Americans died of an opioid overdose in 2021 as the USA continues to struggle with an opioid crisis. Prescription opioids play a substantial role, introducing patients to opioids and providing a supply of drugs that can be redirected to those seeking to misuse them. METHODS: The Drug Enforcement Administration annual summary reports from the Automation of Reports and Consolidated Orders System provided weights of oxycodone distributed per state by business type (pharmacies, hospitals and practitioners). Weights were converted to morphine milligram equivalents (MME) per capita and normalised for population. The Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research provided mortality data for heroin, other opioids, methadone, other synthetic narcotics and other/unspecified narcotics. RESULTS: There was a sharp 280.13% increase in total MME/person of oxycodone from 2000 to 2010, followed by a slower 54.34% decrease from 2010 to 2021. Florida (2007-2011), Delaware (2003-2020) and Tennessee (2012-2021) displayed consistent and substantial elevations in combined MME/person compared with other states. In the peak year (2010), there was a 15-fold difference between the highest and lowest states. MME/person from only pharmacies, which constituted >94% of the total, showed similar results. Hospitals in Alaska (2000-2001, 2008, 2010-2021), Colorado (2008-2021) and DC (2000-2011) distributed substantially more MME/person over many years compared with other states. Florida stood out in practitioner-distributed oxycodone, with an elevation of almost 15-fold the average state from 2006 to 2010. Opioid-related deaths increased +806% from 2000 to 2021, largely driven by heroin, other opioids and other synthetic narcotics. CONCLUSIONS: Oxycodone distribution across the USA showed marked differences between states and business types over time. Investigation of opioid policies in states of interest may provide insight for future actions to mitigate opioid misuse.

First generation antipsychotic-associated serious adverse events in women: a retrospective analysis of a pharmacovigilance database.

BACKGROUND: Women have been under-represented in trials of antipsychotic medications. AIM: Our primary objective was to evaluate five adverse events (AE) associated with first-generation antipsychotics (FGAs) among women relative to men through an analysis of the FDA Adverse Event Reporting System (FAERS). METHOD: We queried 24.6 million AE reports from 2000 to 2023 involving FGAs. The study cohort consisted of chlorpromazine (n = 3317), fluphenazine (n = 1124), haloperidol (n = 16,709), loxapine (n = 3151), perphenazine (n = 816), thioridazine (n = 665), thiothixene (n = 244), and trifluoperazine (n = 360). Cases of neuroleptic malignant syndrome (NMS), tardive dyskinesia (TD), Torsades de Pointes (TdP), agranulocytosis (AG), and cerebrovascular adverse events (CVAE) were identified. Reporting odds ratios (ROR) and associated 95% confidence intervals (CI) were calculated with logistic regression for each AE among women relative to men. RESULTS: A total of 2,857 serious AEs were evaluated in the study cohort (NMS = 1810, TD = 434, TdP = 260, AG = 149, CVAE = 204). The ROR for women compared to men was 0.79 (95% CI, 0.71-0.87) for NMS, 0.83 (0.68-1.01) for TD, 1.21 (0.94-1.53) for TdP, 0.71 (0.51-0.98) for AG, and 0.91 (0.68-1.19) for CVAE. A secondary analysis revealed a higher odds in women compared to men of hospitalization associated with reports of TD (ROR = 1.95, 1.29-2.94) and death associated with reports of AG (ROR = 2.46, 1.15-5.24). A subgroup analysis of haloperidol revealed an ROR = 1.67 (1.26-2.21) for women relative to men for TdP. CONCLUSION: The subgroup analysis of haloperidol AEs revealed a significantly higher reporting odds ratio for TdP. Additionally, the secondary study findings suggest that women were more vulnerable to worse outcomes associated with certain AEs of FGAs.

Undisclosed financial conflicts of interest in DSM-5-TR: cross sectional analysis.

OBJECTIVE: To assess the extent and types of financial ties to industry of panel and task force members of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, fifth edition, text revision (DSM-5-TR), published in 2022. DESIGN: Cross sectional analysis. SETTING: Open Payments database, USA. PARTICIPANTS: 92 physicians based in the US who served as members of either a panel (n=86) or task force (n=6) on the DSM-5-TR with information recorded in the Centers for Medicare and Medicaid Services Open Payments database during 2016-19. This period was chosen to include the year that development of the DSM-5-TR began and the three years preceding, a time consistent with previous research on conflicts of interest and consistent with the American Psychiatric Association's disclosure requirements for the fifth revision (DSM-5) of the manual. MAIN OUTCOME MEASURES: Type and amount of compensation the panel and task force members of DSM-5-TR received during 2016-19. RESULTS: After duplicate names had been removed, 168 individuals were identified who served as either panel or task force members of the DSM-5-TR. 92 met the inclusion criteria of being a physician who was based in the US and therefore could be included in Open Payments. Of these 92 individuals, 55 (60%) received payments from industry. Collectively, these panel members received a total of $14.2m (£11.2m; €13m). One third (33.3%) of the task force members had payments reported in Open Payments. CONCLUSIONS: Conflicts of interest among panel members of DSM-5-TR were prevalent. Because of the enormous influence of diagnostic and treatment guidelines, the standards for participation on a guideline development panel should be high. A rebuttable presumption should exist for the Diagnostic and Statistical Manual of Mental Disorders to prohibit conflicts of interest among its panel and task force members. When no independent individuals with the requisite expertise are available, individuals with associations to industry could consult to the panels, but they should not have decision making authority on revisions or the inclusion of new disorders.

Declining but Pronounced State-Level Disparities in Prescription Opioid Distribution in the United States.

The United States (US) opioid epidemic is a persistent and pervasive public health emergency that claims the lives of over 80,000 Americans per year as of 2021. There have been sustained efforts to reverse this crisis over the past decade, including a number of measures designed to decrease the use of prescription opioids for the treatment of pain. This study analyzed the changes in federal production quotas for prescription opioids and the distribution of prescription opioids for pain and identified state-level differences between 2010 and 2019. Data (in grams) on opioid production quotas and distribution (from manufacturer to hospitals, retail pharmacies, practitioners, and teaching institutions) of 10 prescription opioids (codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, and tapentadol) for 2010 to 2019 were obtained from the US Drug Enforcement Administration. Amounts of each opioid were converted from grams to morphine milligram equivalent (MME), and the per capita distribution by state was calculated using population estimates. Total opioid production quotas increased substantially from 2010 to 2013 before decreasing by 41.5% from 2013 (87.6 MME metric tons) to 2019 (51.3). The peak year for distribution of all 10 prescription opioids was between 2010 and 2013, except for codeine (2015). The largest quantities of opioid distribution were observed in Tennessee (520.70 MME per person) and Delaware (251.45) in 2011 and 2019. There was a 52.0% overall decrease in opioid distribution per capita from 2010 to 2019, with the largest decrease in Florida (-61.6%) and the smallest in Texas (-18.6%). Southern states had the highest per capita distribution for eight of the ten opioids in 2019. The highest to lowest state ratio of total opioid distribution, corrected for population, decreased from 5.25 in 2011 to 2.78 in 2019. The mean 95th/5th ratio was relatively consistent in 2011 (4.78 ± 0.70) relative to 2019 (5.64 ± 0.98). This study found a sustained decline in the distribution of ten prescription opioids during the last five years. Distribution was non-homogeneous at the state level. Analysis of state-level differences revealed a fivefold difference in the 95th:5th percentile ratio between states, which has remained unchanged over the past decade. Production quotas did not correspond with the distribution, particularly in the 2010-2016 period. Future research, focused on identifying factors contributing to the observed regional variability in opioid distribution, could prove valuable to understanding and potentially remediating the pronounced disparities in prescription opioid-related harms in the US.

Pronounced Regional Variation in Esketamine and Ketamine Prescribing to US Medicaid Patients.

Ketamine and esketamine are efficacious for treatment-resistant depression. Unlike other antidepressants, ketamine lacks a therapeutic delay and decreases the risk for suicide. This cross-sectional study geographically characterized ketamine and esketamine prescribing to United States (US) Medicaid patients. Ketamine and esketamine prescription rates and spending per state were obtained. Between 2009 and 2020, ketamine prescribing rates peaked in 2013 followed by a general decline. For ketamine and esketamine in 2019, Montana (967/million enrollees) and Indiana (425) showed significantly higher prescription rates, respectively, relative to the national average. A total of 21 states prescribed neither ketamine nor esketamine in 2019. There was a 121.3% increase in esketamine prescriptions from 2019 to 2020. North Dakota (1,423) and North Carolina (1,094) were significantly elevated relative to the average state for esketamine in 2020. Ten states prescribed neither ketamine nor esketamine in 2020. Medicaid programs in 2020 spent 72.7-fold more for esketamine ($25.3 million) than on ketamine (0.3 million). Despite the effectiveness of ketamine and esketamine for treatment-resistant depression and anti-suicidal properties, their use among Medicaid patients was limited and highly variable in many areas of the US. Further research to better understand the origins of this state-level variation is needed.

Pronounced State-Level Disparities in Medicaid Prescribing of Buprenorphine for Opioid Use Disorder (2019-2020).

OBJECTIVE: The purpose of this study was to analyze buprenorphine prescribing across states in Medicaid patients during 2019-2020. METHOD: Buprenorphine prescriptions per Medicaid enrollee per state were calculated for 2019 and 2020. Data analysis was conducted with buprenorphine formulations that are approved by the U.S. Food & Drug Administration for opioid use disorder (OUD; including generic and brand name formulations of buprenorphine mono product and buprenorphine/naloxone combination products) using Microsoft Excel. The totals of mono product buprenorphine were divided over the total of combination buprenorphine/naloxone in 2019 and 2020 to obtain the ratio of mono/combo. Formulations of buprenorphine indicated for pain were excluded. States outside 95% confidence intervals (1.96 standard deviations above and below the mean) were considered statistically significant. RESULTS: The overall change in buprenorphine prescribing between 2019 and 2020 was modest (+3.6%) but highly variable, with more than a 10% increase in 17 states (Iowa = +100.5%, p < .05) but more than a 10% decrease in 9 states (Alabama = -68.5%, p < .05). Total amount reimbursed in 2019 increased (+9.9%) to $1.42 billion in 2020. Branded formulations accounted for two fifths (39.5%) of prescribing but more than two thirds (66.8%) of spending in 2020. CONCLUSIONS: The COVID-19 pandemic exacerbated state-level disparities in buprenorphine prescribing for OUD among Medicaid patients. Legislation expanding buprenorphine-waivered providers and Medicaid expansion may have contributed to the statistically significant changes in state buprenorphine prescriptions.

Knowledge, Attitudes, and Beliefs of Medical Students Toward Transgender Healthcare: A Community-Driven Initiative.

Introduction Transgender patients face substantial systemic healthcare barriers and inadequate care from providers who often demonstrate clinical gaps in the medical needs of the transgender community. Providing interventions in which affirming transgender healthcare is explored, is crucial to delivering competent transgender-patient care and building compassionate physician-patient relationships. The Northeast Pennsylvania (NEPA) Trans Health Conference was established to address the growing need for an educational forum where transgender people could voice their narratives. In this educational intervention study, changes in the knowledge, attitudes, and beliefs about the psychosocial and medical needs of the transgender community in first-year undergraduate medical students were examined pre- and post-trans health conference attendance. Materials and methods In the late spring of both 2018 and 2019, first-year medical students attended the NEPA Trans Health Conference, hosted by the Geisinger Commonwealth School of Medicine (GCSOM). Student knowledge, attitudes, and beliefs, regarding the healthcare needs of the transgender community were evaluated prior to and directly after the conference (intervention). Though the surveys shared thematic similarities, the 2018 and 2019 surveys were different and thus were not used comparatively. Results In 2018, 35.24% of first-year medical students (37/105 participants) completed both the pre- and post-survey. Overall, 62.5% (5/8) of survey items yielded significant differences. In 2019, 25.5%, of first-year medical students (28/110 participants) completed both the pre- and post-survey and 47.6% (9/21) of survey items yielded significant results. Overall, although the majority of first-year medical students displayed positive attitudes toward trans people pre-intervention, the students also demonstrated increased knowledge, empathy, and understanding of the transgender healthcare narrative post-intervention. Conclusion Providing medical students with a humanistic intervention within the medical curriculum that is focused on the transgender person, in addition to their past and present healthcare experiences, offers a bridge between academic content and providing inclusive gender-affirming healthcare to all patients.

Dynamic changes in methadone utilisation for opioid use disorder treatment: a retrospective observational study during the COVID-19 pandemic.

OBJECTIVES: Opioid use disorder (OUD) is a major public health concern in the USA, resulting in high rates of overdose and other negative outcomes. Methadone, an OUD treatment, has been shown to be effective in reducing the risk of overdose and improving overall health and quality of life. This study analysed the distribution of methadone for the treatment of OUD across the USA over the past decade and through the COVID-19 pandemic. DESIGN: Retrospective observational study using secondary data analysis of the Drug Enforcement Administration and Medicaid Databases. SETTING: USA. PARTICIPANTS: Patients who were dispensed methadone at US opioid treatment programmes (OTPs). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were the overall pattern in methadone distribution and the number of OTPs in the USA per year. The secondary outcome was Medicaid prescriptions for methadone. RESULTS: Methadone distribution for OUD has expanded significantly over the past decade, with an average state increase of +96.96% from 2010 to 2020. There was a significant increase in overall distribution of methadone to OTP from 2010 to 2020 (+61.00%, p<0.001) and from 2015 to 2020 (+26.22%, p<0.001). However, the distribution to OTPs did not significantly change from 2019 to 2021 (-5.15%, p=0.491). There was considerable state-level variation in methadone prescribing to Medicaid patients with four states having no prescriptions. CONCLUSIONS: There have been dynamic changes in methadone distribution for OUD. Furthermore, pronounced variation in methadone distribution among states was observed, with some states having no OTPs or Medicaid coverage. New policies are urgently needed to increase access to methadone treatment, address the opioid epidemic in the USA and reduce overdose deaths.

Medical Cannabis Legalization: No Contribution to Rising Stimulant Rates in the USA.

INTRODUCTION: There has been a pronounced increase in the use of Schedule II stimulants to treat attention-deficit hyperactivity disorder (ADHD) in the United States over the last two decades. Interestingly, chronic medical cannabis (MC) use can present with cognitive impairments that resemble ADHD symptoms. This study aimed to determine if MC legalization increased prescription stimulant distribution. METHODS: Information on the distribution of methylphenidate, amphetamine, and lisdexamfetamine for 2006 to 2021 was extracted from the Drug Enforcement Administration's comprehensive database and the three-year population-corrected slopes of stimulant distribution before and after MC program implementation were compared. RESULTS: We found a significant main effect of time (p<0.001); however, contrary to the hypothesis, the sales status of states' MC, did not influence slopes of distribution (p=0.391). There was a significantly large interaction effect of time and MC sales status on slopes of distribution (p<0.001). Slopes of distribution rates of stimulants were significantly lower in states that proceeded to legalize MC prior to MC program implementation than those states that did not (p=0.022). After MC program implementation, however, the distribution rates of the Schedule II stimulants were not significantly different when comparing states with MC sales to those without (p=0.355). DISCUSSION: These findings suggest that MC program legalization did not contribute to certain states having rapid increases in Schedule II stimulant distribution rates over time. Other factors, including the liberalization of the adult ADHD diagnostic criteria in the DSM-5 and the introduction of Binge Eating Disorder, also likely contributed to elevations in stimulant distribution.

An Examination of the Complex Pharmacological Properties of the Non-Selective Opioid Modulator Buprenorphine.

The goal of this review is to provide a recent examination of the pharmacodynamics as well as pharmacokinetics, misuse potential, toxicology, and prenatal consequences of buprenorphine. Buprenorphine is currently a Schedule III opioid in the US used for opioid-use disorder (OUD) and as an analgesic. Buprenorphine has high affinity for the mu-opioid receptor (MOR), delta (DOR), and kappa (KOR) and intermediate affinity for the nociceptin (NOR). Buprenorphine's active metabolite, norbuprenorphine, crosses the blood-brain barrier, is a potent metabolite that attenuates the analgesic effects of buprenorphine due to binding to NOR, and is responsible for the respiratory depressant effects. The area under the concentration curves are very similar for buprenorphine and norbuprenorphine, which indicates that it is important to consider this metabolite. Crowding sourcing has identified a buprenorphine street value (USD 3.95/mg), indicating some non-medical use. There have also been eleven-thousand reports involving buprenorphine and minors (age < 19) at US poison control centers. Prenatal exposure to clinically relevant dosages in rats produces reductions in myelin and increases in depression-like behavior. In conclusion, the pharmacology of this OUD pharmacotherapy including the consequences of prenatal buprenorphine exposure in humans and experimental animals should continue to be carefully evaluated.

Pronounced State-Level Disparities in Prescription of Cannabinoids to Medicaid Patients.

Introduction: Dronabinol is approved in the USA for chemotherapy-induced nausea as well as vomiting and HIV-induced anorexia, while cannabidiol is primarily approved for childhood epileptic disorders Lennox-Gastaut and Dravet syndrome. The use pattern for these prescription cannabinoids in the USA is unknown. This study examined Medicaid claims for two FDA-approved prescription cannabinoids, dronabinol and cannabidiol, approved in 1985 and 2018, respectively, from 2016-2020 to better understand the pharmacoepidemiologic trends and distribution of these drugs in US Medicaid amidst the increasing use of non-pharmaceutical formulations of cannabis. Methods: The longitudinal study analyzed Medicaid prescription claims that were calculated by extracting the prescriptions on a state level from 2016 to 2020 for two cannabinoids, dronabinol and cannabidiol, where outcomes over each year were calculated. Outcomes were (1) the number of prescriptions for each state corrected for the number of Medicaid enrollees and (2) dronabinol and cannabidiol spending. Spending refers to the amount reimbursed by the state Medicaid program. Results: Dronabinol prescriptions per state decreased by 25.3% from 2016 to 2020, while cannabidiol prescriptions increased by 16,272.99% from 2018 to 2020. The spending on these drugs parallels that of their prescription trend with a 66.3% decrease in reimbursement for dronabinol ($5.7 million in 2020), whereas cannabidiol increased by +26,582.0% ($233.3 million in 2020). Dronabinol prescriptions, when corrected for the number of enrollees, in Connecticut were 136.4 times larger than in New Mexico, and seventeen states had zero prescriptions. Idaho's prescriptions of cannabidiol (27.8/10,000 enrollees) were significantly elevated relative to the national average and were 15.4-fold higher than Washington, DC (1.8/10K enrollees). Conclusions: The prescriptions of pharmaceutical-grade tetrahydrocannabinol decreased while those of cannabidiol increased. This study also identified pronounced state-level variation in cannabinoid prescribing to Medicaid patients. State formularies and prescription drug list variation may contribute to the drug reimbursements in Medicaid, though further research is needed to identify the health policy or pharmacoeconomic origins of these disparities.

An analysis of patterns of distribution of buprenorphine in the United States using ARCOS, Medicaid, and Medicare databases.

Opioid overdose remains a problem in the United States despite pharmacotherapies, such as buprenorphine, in the treatment of opioid use disorder. This study characterized changes in buprenorphine use. Using the Drug Enforcement Administration's ARCOS, Medicaid, and Medicare claims databases, patterns in buprenorphine usage in the United States from 2018 to 2020 were analyzed by examining percentage changes in total grams distributed and changes in grams per 100 K people in year-to-year usage based on ZIP code and state levels. For ARCOS from 2018 to 2019 and 2019 to 2020, total buprenorphine distribution in grams increased by 16.2% and 12.6%, respectively. South Dakota showed the largest statewide percentage increase in both 2018-2019 (66.1%) and 2019-2020 (36.7%). From 2018 to 2019, the ZIP codes ND-577 (156.4%) and VA-222 (-82.1%) had the largest and smallest percentage changes, respectively. From 2019 to 2020, CA-932 (250.2%) and IL-603 (-36.8%) were the largest and smallest, respectively. In both 2018-2019 and 2019-2020, PA-191 had the second highest increase in grams per 100K while OH-452 was the only ZIP code to remain in the top three largest decreases in grams per 100K in both periods. Among Medicaid patients in 2018, there was a nearly 2000-fold difference in prescriptions per 100k Medicaid enrollees between Kentucky (12 075) and Nebraska (6). Among Medicare enrollees in 2018, family medicine physicians and other primary care providers were the top buprenorphine prescribers. This study not only identified overall increases in buprenorphine availability but also pronounced state-level differences. Such geographic analysis can be used to discern which public policies and regional factors impact buprenorphine access.

The Neurobiology of Methamphetamine Addiction and the Potential to Reduce Misuse Through Conjugate Vaccines Targeting Toll-Like Receptor 4.

The methamphetamine epidemic continues to worsen each year and has contributed to more overdose deaths than opioids. Methamphetamine was listed in the top ten lethal drugs in 2021 in the United States. The drug has been shown to cause health problems such as addiction and neurological and behavioral changes. One possible solution to address this crisis is through vaccinations. Vaccinations consist of injecting a controlled substance with the goal of creating compound-specific antibodies. Although still early in development, vaccinations have been found to improve withdrawal symptoms and decrease drug-seeking behavior with minimal health side effects in rodent studies. This paper provides an overview of the clinical presentation and neurobiology of methamphetamine addiction and drug-seeking behaviors. The responses and adverse effects of conjugate vaccines IXTv-100 with adjuvant glucopyranosyl lipid A administered in oil-water stable emulsion and tetanus-toxoid conjugated to succinyl-methamphetamine adsorbed on aluminum hydroxide combined with adjuvant E6020 are examined.

Regional Disparities in Prescription Methamphetamine and Amphetamine Distribution Across the United States.

OBJECTIVE: The objectives of this report were to characterize the regional and state differences in prescription methamphetamine and amphetamine distribution in the US. METHODS: Prescription methamphetamine and amphetamine distribution was obtained from the Drug Enforcement Administration for 2019. RESULTS: Total per capita drug weight distribution of amphetamine was 4,000 times higher than methamphetamine. Regionally, total per capita drug weight for methamphetamine was highest in the West (32.2% of total distribution) and lowest in the Northeast (17.4%). The total per capita drug weight for amphetamine was highest in the South (37.0% of total distribution) and lowest in the Northeast (19.4%). Distribution of methamphetamine was 16.1% while amphetamine was 54.0% of its production quota. CONCLUSION: Overall, prescription amphetamine distribution was common while prescription methamphetamine distribution was rare. The patterns observed in distribution are likely the result of stigmatization, differences in accessibility, and the efforts of initiatives such as the Montana Meth Project.

High Prescribing and State-Level Variation in Z-Drug Use Among Medicare Patients.

BACKGROUND: Z-drugs are nonbenzodiazepine hypnotics used for sleep initiation and maintenance; these drugs increase the risk of fall-related injuries in older adults. The American Geriatrics Society's Beers criteria classifies Z-drugs as high-risk and strongly recommends avoiding prescribing Z-drugs to older adults due to adverse effects. The study objectives were to determine the prevalence of Z-drug prescribing among Medicare Part D patients and identify state or specialty-dependent prescribing differences. This study also aimed to determine prescribing patterns of Z-drugs to Medicare patients. METHODS: Z-drug prescription data was extracted from the Centers for Medicare and Medicaid Services State Drug Utilization Data for 2018. For all 50 states, the number of prescriptions per 100 Medicare enrollees and days-supply per prescription was determined. The percentage of total prescriptions prescribed by each specialty and the average number of prescriptions per provider within each specialty was also determined. RESULTS: Zolpidem was the most prescribed Z-drug (95.0%). Prescriptions per 100 enrollees were significantly high in Utah (28.2) and Arkansas (26.7) and significantly low in Hawaii (9.3) relative to the national average (17.5). Family medicine (32.1%), internal medicine (31.4%), and psychiatry (11.7%) made up the largest percentages of total prescriptions. The number of prescriptions per provider was significantly high among psychiatrists. DISCUSSION: Contrary to the Beers criteria, Z-drugs are prescribed to older adults at high rates.

An Analysis of Oxycodone and Hydrocodone Distribution Trends in Delaware, Maryland, and Virginia Between 2006 and 2014.

Objective Opioid medications are widely recognized for their use in analgesia and their addictive properties that have led to the opioid epidemic. Areas with historically high prescribing patterns have been shown to suffer more from the crisis. There is also regional variability in these trends. This study is a county level analysis of oxycodone and hydrocodone use in Delaware, Maryland, and Virginia between 2006 and 2014. Materials and methods A retrospective analysis of oxycodone and hydrocodone distributed as collected by the Drug Enforcement Administration's (DEA) Washington Post Automation of Reports and Consolidated Orders System (ARCOS) in Delaware, Maryland, and Virginia. Raw drug weights in each county were adjusted to "daily average dose" (grams/county population/365) using publicly available population estimates for all state counties. Purchasing data collected from ARCOS was used to compare distribution trends during this period. This study was limited in that ARCOS report quantity of drug distribution rather than average dose of script written.  Results There was a 57.59% increase in the weight of oxycodone and hydrocodone prescribed between 2006 and 2014. Oxycodone prescriptions increased by 75.50% and hydrocodone by 11.05%. Oxycodone increased across all three states between 2006 and 2010 and declined until 2014. Hydrocodone also increased but to a lesser extent than oxycodone. There was substantial variability in daily average dose of both opioids at the county level in all states. Pharmacies accounted for largest portion of oxycodone (69.17%) and hydrocodone (75.27%) purchased in the region. Hospitals accounted for 26.67% of oxycodone and 22.76% of hydrocodone purchased. Practitioners and mid-level providers, including Nurse Practitioners and Physician Assistants, did not significantly contribute to this increase. Conclusion In the states of Maryland, Delaware, and Virginia, the distribution of the prescription opioids oxycodone and hydrocodone increased by 57.59%. Daily average dose increased between 2006 and 2010 in all three states, followed by a decline until 2014. Variability in daily average dose by county highlights the relationship between geography and likelihood of receiving high-dose opioids. Increased monitoring at regional health centers and improving substance abuse treatment infrastructure at the county level may be a more efficient strategy in combating the opioid epidemic. Future research is needed to understand the socioeconomic trends that may influence prescribing trends of opioid medications.