Drug Enforcement Administration Research Articles

Protocol for the development of a consensus practice guideline To address clinical and regulatory barriers to buprenorphine dispensing in community pharmacy

BackgroundLess than half of community pharmacies in the United States stock buprenorphine products indicated for the treatment of opioid use disorder. This lack of access to buprenorphine in community pharmacies is a significant barrier to care. To address this issue, this protocol outlines a comprehensive approach to develop a practice guideline aimed at improving access to safe and effective opioid use disorder treatment in community pharmacies.MethodsThe guideline development process will proceed in three phases, following a technique closely aligned with the Institute of Medicine’s guidance on guideline development. The first phase will involve conducting qualitative interviews with pharmacists in three states to identify their beliefs toward buprenorphine dispensing. As limitations on buprenorphine supply are related to constraints at all levels of the drug supply and regulatory system, the second phase, we will recruit representatives from regulatory agencies, pharmacy organizations, the Drug Enforcement Administration, pharmaceutical wholesalers as well as addiction medicine physicians and psychiatric pharmacists to develop consensus recommendations through a modified Delphi design. This will be followed by a public comment period and external expert review of the recommendations led by the National Association of Boards of Pharmacy. Finally, in the third phase, a national, mixed media dissemination campaign will be led by the National Community Pharmacists Association (NCPA) to convey recommendations to practicing pharmacists.DiscussionThe guideline development process aims to incorporate the perspectives of multiple stakeholders and emphasize the importance of addressing the regulatory and pharmacy-specific aspects of care in addition to clinical evidence and guidance. The development of this guideline will provide targeted, multidisciplinary guidance for pharmacists, improving access to safe and effective opioid use disorder treatment in the community setting.PreregistrationThis protocol was registered with the Open Science Framework in March of 2023. Registration may be found at: https://doi.org/10.17605/OSF.IO/6S9DY.

Hiding Behind Complexity: Supply Chain, Oversight, Race, and the Opioid Crisis

The opioid crisis has ravaged the United States, taking 69,000 lives in 2020, with prescription opioids accounting for 98% of opioid abuse. Although this epidemic is often considered a White public health crisis nationally, overdose deaths among people of color doubled from 2017 to 2019. As research has shown that the crisis was fueled by excessive supply from the pharmaceutical industry, several individual firms have received significant public criticism. However, we find evidence that the scope of the blame transcends individual actors to indict the very structure of complex supply chains, which may have exacerbated the crisis by dispensing significantly more opioids. In specific, we posit that supply chain complexity allowed mass quantities of opioids to escape detection by the Drug Enforcement Administration (DEA). Further, we find new evidence showing the greater impact of complexity on opioid dispensing in non-White communities, which underscores their exclusion from the public discourse and governmental response surrounding the crisis and suggests possible racial bias in the DEA’s regulatory policies. Our analysis was made possible by the 2019 release of the DEA’s Automation of Reports and Consolidated Orders System database, which logged every shipment in the US opioid supply chain from 2006 to 2014. Using a fixed effects model, we find that a one-unit increase across three dimensions of supply chain complexity is associated with a 16% increase in opioid dispensing. This effect is intensified in non-White communities, where a 10% increase in the non-White population is associated with a 3.39% (1.33%) increase in opioid dispensing by pharmacies that have supply chains with high (average) complexity. To verify that high-complexity pharmacies’ excess dispensing supplied non-medical/recreational demand, we exploit the reformulation of OxyContin (designed to prevent recreational use) as an exogenous shock to the market. In a novel approach, we leverage the fact that different pharmacies received their first shipment of reformulated OxyContin at different times and use a difference-in-differences model to estimate the heterogeneous effect of the shock on dispensing. As the reformulated OxyContin stifled demand, high-complexity pharmacies experienced a 15.31% greater reduction in dispensing compared to lower-complexity pharmacies, suggesting that their excess dispensing was indeed satisfying non-medical/recreational demand.

Primary care professionals' perspectives on tailoring buprenorphine training for rural practice.

Buprenorphine is a highly effective medication for opioid use disorder (OUD) that remains substantially underutilized by primary care professionals (PCPs). This is particularly true in rural communities, which have fewer prescribers and significant access disparities. The Drug Enforcement Administration removed the X-waiver requirement in December 2022, yet many rural clinicians still report barriers to prescribing buprenorphine. In this study, we examined rural PCPs' experiences with buprenorphine to identify tailored training strategies for rural practice. Physicians, nurse practitioners, and physician associates practicing in rural Ohio counties were recruited through contacts at statewide health associations and health professions training programs. Twenty-three PCPs were interviewed about their perspectives on prescribing buprenorphine, including their training history. PCPs self-reported being motivated to respond to OUD. However, they also reported that current training efforts failed to equip them with the knowledge and resources needed to prescribe effectively, and that urban-focused training often alienated rural clinicians. Participants suggested tailoring training content to rural settings, using rural trainers, and bolstering confidence in navigating rural-specific barriers, such as resource deficits and acute opioid fatigue. Our study found that current training on buprenorphine prescribing is inadequate for meeting the needs of rural PCPs. Tailored buprenorphine training is needed to improve accessibility and acceptability, and to better support the clinical workforce in communities disproportionately impacted by the opioid epidemic.

Xylazine: An Abused Tranq Dope and its Safety Concern.

A drug called Xylazine has gained notoriety in recent times, earning the nickname "zombie drug" due to reported alarming effects on its users. Although Xylazine is primarily intended for veterinary use as a sedative and muscle relaxant for animals, there have been growing concerns about its misuse among humans, particularly in the context of illicit drug use. However, it is essential to rely on accurate and evidence-based information when discussing the health risks associated with any substance, rather than resorting to sensationalized terms like "zombie drug." The situation involving Xylazine misuse is a matter of concern, and the United States Drug Enforcement Administration has highlighted it as a significant threat to public health.

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

ObjectivesThis study aims to characterise oxycodone’s distribution and opioid-related overdoses in the USA by state from 2000 to 2021.DesignThis is an observational study.SettingMore than 80 000 Americans died of an...

Leveraging prescription monitoring program data to evaluate the implementation of buprenorphine telehealth flexibilities: An interrupted time series analysis in Texas

BackgroundIn March 2020, policy changes by the Substance Abuse and Mental Health Services Administration and the Drug Enforcement Administration aimed to maintain access to office-based opioid treatment services by easing telehealth buprenorphine prescribing restrictions. However, the effectiveness of these changes remains largely unmeasured. The objective of this study was to measure the effectiveness of COVID-19-related telehealth flexibilities in an all-payer cohort from the Texas Prescription Monitoring Program. MethodsUsing Texas Prescription Monitoring Program data, we identified oral buprenorphine and buprenorphine/naloxone prescriptions dispensed in Texas between September 1, 2019, and September 26, 2020. Weekly counts of prescriptions, prescribing physicians, and dispensing pharmacies were analyzed. An autoregressive integrated moving average (ARIMA) model estimated changes in prescription volume between pre-implementation (September 1, 2019 - February 15, 2020) and post-implementation (April 12, 2020 - September 26, 2020) periods. ResultsPre-flexibility, an average of 8898 (SD: 342) buprenorphine prescriptions were dispensed to 7829 (SD: 326) patients weekly. This declined to 8360 (SD: 247) prescriptions and 7661 (SD: 229) patients post-flexibility. Adjusted for seasonality, this represented a statistically significant average decline of −257.27 (95% CI: −426.06, −88.49) patients and −647.01 (95% CI: −856.67, −437.36) prescriptions per week. DiscussionOur results suggest a modest decline in buprenorphine dispensing volume early in the COVID-19 pandemic. While difficult to assess its significance, it can be assumed that telehealth flexibilities mitigated a potentially larger decline. Future research should explore system and individual-level barriers to telehealth utilization.

OTPs gladly plan to implement new methadone rules

On Feb. 2 the Substance Abuse and Mental Health Services Administration (SAMHSA) released its final rule for opioid treatment programs and methadone, just as ADAW went to press (see SAMHSA issues final rule updating OTP methadone rules, ADAW Feb. 5; https://onlinelibrary.wiley.com/doi/10.1002/adaw.34023). The American Association for the Treatment of Opioid Dependence (AATOD), which represents more than 1,300 opioid treatment programs (OTPs) in the United States, last week commended SAMHSA for the guidance, which it called “enlightened and thoughtful.” In a Feb. 5 press statement, AATOD president Mark Parrino noted that the regulations have been reviewed by the Drug Enforcement Administration (DEA). For the final rule, go to https://www.federalregister.gov/documents/2024/02/02/2024‐01693/medications‐for‐the‐treatment‐of‐opioid‐use‐disorder.

Dialing for doctors: Secret shopper study of Arizona methadone and buprenorphine providers, 2022

IntroductionMethadone and buprenorphine are effective and safe treatments for opioid use disorder (OUD) and also reduce overdose and all-cause mortality. Identifying and reaching providers of medication for opioid use disorder (MOUD) has proven difficult for prospective patients and researchers. ObjectivesTo assess the accuracy of government-maintained lists of Arizona (AZ) providers prescribing MOUD, and the extent to which these providers are accessible for treatment. MethodsA two-phase study used a listing of 2376 AZ MOUD providers obtained from the U.S. Drug Enforcement Administration and the Substance Abuse and Mental Health Services Administration. Phase 1 assessed the accuracy of the listing using internet confirmatory research from May–October 2022. Phase 2 used the resulting list of 838 providers to assess provider availability, type of MOUD treatment provided, and accepted payment through secret shopper calls between November 16 and 30, 2022. ResultsJust over half (52.2 %, n = 1240) of providers were removed from the original listing during Phase 1. One quarter (25.9 %) were no longer in practice. Among the 833 eligible for the secret shopper Phase 2 study, 36.6 % (n = 307) were reached and identified as providing MOUD. A vast majority (88.1 %) of MOUD providers indicating treatment type were accepting new patients, however methadone was identified far more frequently than was likely permitted or provided for OUD. Providers were 5.5 times more likely to accept new patients if they accepted cash payment for services, and 4.9 times more likely if they accepted Medicaid. Rural areas remained underserved. ConclusionsThe active population of MOUD providers is far smaller than surmised. DEA and SAMHSA provider listings are not sufficiently accurate for survey research sampling. Other means of representative sampling will need to be devised, and trusted lists of providers for prospective patients should be promoted, publicly available, and regularly maintained for accuracy. Providers that offer treatment should assure that public-facing staff have basic information about the practice, the treatment offered, and conditions for taking new patients. Concerted efforts must assure rural access at the most local levels to reduce patient travel burden.

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.

Association between high-threshold practices and buprenorphine treatment termination

BackgroundRegular counseling and frequent drug testing are common requirements for patients with opioid use disorder in buprenorphine treatment. State policies throughout the United States often reinforce these high-threshold practices, as was the case with Michigan, USA. MethodsWe sought to explore the association between counseling requirements, drug testing practices, and buprenorphine treatment termination rates through administering a survey to buprenorphine prescribers in Michigan. ResultsIn our sample of 377 prescribers, we found associations between high-threshold practices like drug testing at every clinical visit and requiring counseling and buprenorphine treatment termination rates. Relative to prescribers who randomly drug tested, drug tested at fixed intervals, or did not require any drug testing, prescribers who drug-tested patients at every visit were 38% more likely to terminate treatment. Prescribers who required counseling were 33% more likely to terminate treatment than those who did not require counseling. ConclusionWith the elimination of the USA Drug Enforcement Administration X-waiver in December 2022, state policies need to minimize high-threshold practices that reduce buprenorphine treatment continuity and undermine an effective response to the overdose crisis.

Addressing buprenorphine supply barriers: A guidance commentary

The current supply-side constraints limiting buprenorphine availability at pharmacies may reduce the potential impact of recent initiatives to improve medications for opioid use disorder (MOUD) access. The recent opioid litigation combined with existing federal regulation and enforcement has resulted in significant restrictions to the distribution and dispensing practices of pharmaceutical wholesalers and pharmacies countrywide. Previously discussed solutions to these problems do not seem to have produced actionable improvements to the current landscape. However, a novel solution to this problem may exist in the form of a Drug Enforcement Administration (DEA) guidance letter.These guidance letters allow the DEA to communicate directly to registrants, providing detailed interpretation and clarity regarding the DEA’s expectations and enforcement realities. Recently, the DEA guidance letter portal was used to remind registrants that the DEA does not create quantitative thresholds or volume limits on controlled substance distribution. An additional guidance letter could be issued to ease the concerns about liability connected to the distribution and dispensing of buprenorphine. In particular, this guidance could acknowledge certain terms of the distributor settlement agreement as legal precedent and clarify that buprenorphine is not subject to the same restriction as other defined “highly diverted” controlled substances. Such guidance may also serve to provide both pharmaceutical wholesalers and pharmacies with assurance that an increase in buprenorphine distribution would not directly result in increased DEA scrutiny. This strategy represents an actionable step toward the goal of providing better access to MOUD by reducing existing supply-side limitations.

The Psychiatrist's Role in Treating Perinatal Opioid Use Disorder and Reducing Maternal Mortality.

Drug overdose is a leading cause of maternal mortality. Psychiatrists can play a critical role in reducing these deaths by delivering effective evidence-based treatments for perinatal opioid use disorder (POUD), including the use of buprenorphine. Medications for POUD (i.e., buprenorphine, methadone) are life-saving treatments, but only half of those who are diagnosed as having POUD will receive this treatment, which can result in an increased risk for return to opioid use, overdose, and death. Psychiatrists are well positioned to prescribe buprenorphine given the Drug Enforcement Administration's (DEA) removal of the requirement to submit a Notice of Intent to prescribe buprenorphine for the treatment of opioid use disorders. Psychiatrists who have a current DEA registration that includes Schedule III authority may now prescribe buprenorphine for opioid use disorders; the training requirements to do so are outlined herein. This article reviews the standard of care for screening, diagnosis, and treatment of POUD, and prescribing buprenorphine for POUD, as well as shared decision-making for medication selection, induction, and maintenance of buprenorphine during pregnancy, labor and delivery, and the postpartum year.

미국 마약 통합 관리 시스템을 통한 한국의 마약정책 고찰

New Psychoactive Substances (NPS) are spreading like a trend around the world, and the number of drug crimes is increasing more than ever as distribution methods evolve day by day. Recently, as the drug problem has become increasingly serious, it has become an unbearable reality with the functions and roles of existing drug-related institutions. Most countries use a combination of criminal justice punishment models that control and deter drug supply to make the drug-free society and medical & treatment models that rehabilitate addicts. In other words, supply control policies rely mainly on thorough crackdowns and strong punishment, and demand control policies pursue balanced strategies by focusing on prevention in advance through treatment and rehabilitation. However, countries that have implemented most drug policies have experienced many side effects from unbalanced policies and are making great efforts to make balanced policies to solve them. However, the results vary widely depending on the efforts and budgets of each government, also the structure of the organization that manages drugs is diverse. Current study will examine the current status of Korean drug-related institutions and review the U.S. drug integration management system(IMS). And mainly discuss the direction of Korea's drug policy through the background and historical changes of the Drug Enforcement Administration (DEA). It is meaningful in preparing a specific and practical balanced drug policy that can create a drug-free society through the advantages and disadvantages of the U.S. drug IMS . At the conclusion this study establishes a practical national system to efficiently deal with drugs and in turn protect citizen from drugs.

In Case You Haven't Heard…

Federal health authorities have intensified their scrutiny of the drug ketamine for treating mental health disorders as the mind‐altering compound grows in popularity despite the lack of regulatory approval for such use, The Washington Post reported last week. The Food and Drug Administration (FDA) warned in October about the risks of using pharmacy‐made ketamine at home, citing the case of one patient whose breathing slowed to a dangerous level after taking a large dose outside of a health care facility. Then the autopsy of actor Matthew Perry, released Dec. 15, concluded a high dose of ketamine led to his death in October — an event that, while rare, drove home the dark side of the anesthetic that can also be abused recreationally. Meanwhile, the Drug Enforcement Administration continues to craft a rule that would set new limits on how health care professionals can use telemedicine to prescribe tightly regulated drugs like ketamine. Adam Kaplin, who observed the power of ketamine while overseeing clinical trials that led to the approval of Spravato, but also saw the inconvenience and cost that comes with the FDA‐required monitoring, said he is aiming to develop a derivative of ketamine with fewer side effects. The goal, said Kaplin, chief scientific officer of Mira Pharmaceuticals, is to create a drug that the FDA will endorse as safe for patients to take at home.

Differences in buprenorphine prescribing readiness among primary care professionals with and without X-waiver training in the US

BackgroundMedications for opioid use disorder (OUD) are effective at preventing overdose and infectious disease but are vastly under-prescribed in the US. For decades, prescribers faced additional training and regulation to prescribe buprenorphine which stigmatized the medication and lessened support for a harm reduction approach to treating opioid use disorder. The Drug Enforcement Administration removed the X-waiver requirement for prescribing buprenorphine in late 2022, which removed stigma and lessened important barriers to prescribing but also left training at the discretion of individual organizations. Our study aimed to assess differences in knowledge, confidence, and stigma regarding buprenorphine between those who went through the X-waiver training and those who did not, among practicing primary care providers (PCPs).MethodsWe assessed buprenorphine prescribing readiness among primary care aligned outpatient providers in Ohio, USA. Using survey data, we conducted bivariate and regression analyses predicting primary prescribing outcomes. Primary outcomes measured knowledge of and confidence in buprenorphine, as well as perceived adequacy of one’s training. Secondary outcomes were attitudes toward patients with OUD, including bias toward OUD patients, stress when working with them, and empathy toward them. Participants (n = 403) included physicians, nurse practitioners, and physician assistants practicing in primary care aligned disciplines.ResultsSurvey data showed that PCPs who received X-waiver training were more likely to understand and have confidence in the mechanism of buprenorphine, and consider their training on treating OUD to be adequate. PCPs with an X-waiver showed more empathy, less negative bias, and experienced less stress when working with patients with OUD.ConclusionRemoving restrictive policies for prescribing buprenorphine is an important step to expanding access and reducing the stigma associated with opioid use disorder treatment. Yet, our findings suggest that the training received alongside regulation may be important for improving prescribing confidence and reducing stigma. Strategies to increase buprenorphine prescribing are unlikely to be effective without also expanding access to prescribing support for primary care providers across the career course.

Operationalizing the new DEA exception: A novel process for dispensing of methadone for opioid use disorder at discharge from acute care settings.

To describe one strategy for dispensing of methadone at emergency department (ED) and hospital discharge implemented within 2 urban academic medical centers. Expanding access to medications for opioid use disorder (OUD) is a national priority. ED visits and hospitalizations offer an opportunity to initiate or continue these lifesaving medications, including methadone and buprenorphine. However, federal regulations governing methadone treatment and significant gaps in treatment availability have made continuing methadone upon ED or hospital discharge challenging. To address this issue, the Drug Enforcement Administration (DEA) granted an exception allowing hospitals, clinics, and EDs to dispense a 72-hour supply of methadone while continued treatment is arranged. Though this exception addresses a critical unmet need, guidance for operationalizing this service is limited. To facilitate expanded patient access to methadone on ED or hospital discharge at 2 Baltimore hospitals, key stakeholders within the parent health system were identified, and a workgroup was formed. Processes were established for requesting, approving, preparing, and dispensing the methadone supply using an electronic health record order set. Multidisciplinary educational materials were created to support end users of the workflow. In the first 3 months of implementation, 42 requests were entered, of which 36 were approved, resulting in 79 dispensed methadone doses. This project demonstrates feasibility of methadone dispensing at hospital and ED discharge. Further work is needed to evaluate impact on patient outcomes, such as hospital and ED utilization, length of stay, linkage to treatment, and retention in treatment.

Buprenorphine Use in the United States, 2010-2019

BackgroundBuprenorphine is effective for the treatment of opioid use disorder and chronic pain, has a safer pharmacological profile than full mu-opioid agonists, and can now be prescribed by any US provider with a Drug Enforcement Administration license. This study aimed to examine a decade of buprenorphine prescribing patterns in the United States. MethodsWe abstracted opioid and buprenorphine prescribing patterns, including patient characteristics, from the 2010-2019 National Ambulatory Medical Care Survey, a national probability sample of non-federal, ambulatory encounters. DISCUSSIONAmong 248,164 ambulatory encounters, opioids were prescribed 2.6%-4.3% of the time with a rate that peaked in 2013 and has been steadily declining. Buprenorphine was infrequently prescribed. Patients receiving buprenorphine were predominantly male (59%), white (70%), younger in age, and had higher rates of substance use disorder (72%). ConclusionBuprenorphine is infrequently used, despite being effective for pain and safer than full mu-opioid agonists. The Drug Enforcement Administration recently ended the requirement for prescribers to obtain an X-waiver, which may increase the rate of buprenorphine use among US practitioners.

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

ObjectivesOpioid 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...

Zuranolone: First Approval.

Zuranolone (ZURZUVAE™) is an oral neuroactive steroid and a positive allosteric modulator of the gamma aminobutyric acid A (GABAA) receptor being developed by Sage Therapeutics and Biogen for the treatment of mood disorders. In August 2023, zuranolone received its first approval in the USA for the treatment of adults with postpartum depression [pending scheduling by the US Drug Enforcement Administration (DEA)]. This article summarizes the milestones in the development of zuranolone leading to this first approval.

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

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. 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. 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). 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.