Schedule I Drug Research Articles

Compliance in the laboratory: Navigating the Controlled Substances Act and Federal Analogue Act in scientific research

This paper delves into the crucial yet complex relationship between federal laws and scientific research, centering on the Controlled Substances Act (CSA) and the Federal Analogue Act (FAA). The CSA classifies substances into schedules, dictating the scope of scientific inquiry, particularly for Schedule I drugs, which have no recognized medical use and high potential for abuse. Researchers interested in these substances face a rigorous registration process, ensuring scientific advancements adhere to legal constraints. On the other hand, the FAA targets substances similar in structure and effect to controlled drugs, treating them as Schedule I if intended for human consumption. This presents a significant challenge to researchers who must meticulously assess legal risks and compliance to avoid inadvertent infringements. Compounds only an atom away from being classified as non-hallucinogenic can skirt the borders of legality, requiring carefully navigated research paths. Within this framework, researchers are tasked with navigating a maze of regulations—securing permits, conducting ethically-approved studies, and keeping detailed records. These efforts are critical for preserving the integrity and legitimacy of scientific work. In summary, the CSA and FAA are cornerstones of legal guidance for research related to controlled substances. They necessitate a proactive, well-informed research approach ensuring adherence to evolving legal standards and reinforcing the foundational values of responsible scientific practice. Compliance with these acts not only mitigates against the proliferation of illicit drugs but also consolidates the ethical pursuit of scientific knowledge.

Trends in co-prescribed opioids and benzodiazepines, non-prescribed opioids and benzodiazepines, and schedule-I drugs in the United States, 2013 to 2019

Concurrent opioid and benzodiazepine users are at increased risk of overdose death, compared to opioid-only users.The objective of this study was to understand recent time trends in opioid and benzodiazepine concurrent use, misuse, and schedule-I drug use, and how these differ by age, sex and geographic region. Commercial, United States medical insurance claims data and urine drug test results from 2013 to 2019 were used to study the outcomes of concurrent use (n = 756,258), schedule-I drug use (n = 746,672) and prescription misuse (n = 452,523). Drug use outcomes were studied at quarterly time points for each year.Data analysis included joinpoint regression models to estimate quarterly drug use rates, determined by positive urine tests for corresponding drug categories, and was conducted from November 2021 through January 2022. Concurrent use decreased from 19.3% to 9.8%, misuse generally decreased from 75.6% to 55.1%, and schedule-I use increased from 8.9% to 13.8%, from 2013 to 2019. Concurrent use decreased at greater rates after 2016, after the Centers for Disease Control and Food and Drug Administration guidelines against concurrent use were released, while schedule-I use increased, notably after the 2014 hydrocodone reschedule. This indicates a potential shift from prescription use to non-prescribed drug use, where most affected groups included males, younger individuals, and those residing in Northeastern regions.Study results support public health initiatives focused on policy that increases access to multimodal pain management and substance use disorder management programs—critical steps in preventing patients from seeking non-prescribed drugs for self- medicating due to pain or addiction.

A regulatory framework review of Schedule I psychedelics in the United States

AbstractPsychoactive substances such as psilocybin and 3,4‐methylenedioxy‐methamphetamine (MDMA) are currently being investigated for a variety of psychiatric indications including major depressive disorder and post‐traumatic stress disorder. It is critical that clinicians working in the mental health field understand the regulatory framework that balances access and control for such substances. While both psilocybin and MDMA are designated as “Breakthrough Therapy” by the Food and Drug Administration (FDA), they remain classified as Schedule I substances under the Controlled Substances Act (CSA) of 1970. There are programs such as Expanded Access (EA) and federal Right‐to‐Try (RTT) legislation that can accommodate patient access to investigational drugs under certain circumstances, but these programs are not without their limits—particularly for Schedule I substances that do not currently have an accepted medical use per the CSA. It is in the clinical community's best interest to understand the administrative procedures, key court cases, and federal legislative initiatives related to these substances in order to make well‐informed decisions for themselves and their patients. Furthermore, understanding the administrative proceedings related to controlled substances will also allow subject matter experts to participate in and shape the policies governing such substances.

Psychedelics Legislation Gains Momentum

Psychedelics Legislation Gains Momentum

Social Justice and Medical Equity through Federal Legalization of Marijuana

Most Americans are living with state-sanctioned cannabis jurisdiction permitting medicinal, and often, recreational use. Yet, cannabis and its cannabinoids remain on schedule-I of the controlled substances act (CSA), imposing hurdles to much needed research and promulgating outdated ‘War on Drugs’ policies and their disproportionate impact on minorities. Recent advances by the current government to decriminalize past federal cannabis possession convictions and the encouragement to State Governors to follow suit are within the current political climate and public opinion but fall short during times of an ever- faster expansion of cannabis legislation and access by the individual states. Opposing views on federal cannabis legalization have precipitated an indeterminate situation between federal and state legislation prompting inconsistent decision-making, social injustice, and health inequities across the country. The latter can be exemplified by the inconsistencies of qualifying conditions and availability of cannabis for medicinal use. Now, under the new 118th U.S. Congress, it becomes ever more important to re-focus on legislative opportunities such as the ‘Marijuana Opportunity Reinvestment and Expungement (MORE) Act of 2021’ which had been previously passed by the House of Representatives on April 1st, 2022, under the 117th Congress (2021-22). This bill aims to de-schedule and decriminalize use, possession, distribution, sale, and production of medical cannabis on the federal level. Through establishing cannabis business equity and loan programs, it seeks to promote social justice for communities disproportionately affected by the ‘War on Drugs’. This health policy research brief provides a comprehensive view of stakeholder perspectives and positions, as well as potential benefits and drawbacks - all with a historical perspective.

Environmental and Processing Contaminants from Pahs and Furan

Maintaining an adequate, safe food supply has been a major goal of the Federal Government since 1906, when the first Federal food and drug law was signed into law. Historically, chemicals such as salt, sugar, and wood smoke have been used to preserve foods. Modern food technology relies extensively on the use of chemicals not only for preservation but also to produce appealing colors, flavors, aromas, and textures. Most developed countries now have food laws designed to permit the use of such chemicals in food under conditions judged to be safe. These chemicals are not considered adulterants or contaminants and are classed as intentional additives. Other chemicals may enter food as a result of their use in food production, handling, or processing. Such substances maybe legally permitted if they are unavoidable under good manufacturing practices and if the amounts involved are considered safe. These chemicals are classed as incidental additives. The presence of both these classes of chemicals in food is controlled by regulation.

Drug trafficking, good faith, and legal standards to convict: How the United States Supreme Court is about to affect every prescriber in America.

Dr. Xiulu Ruan was a pain specialist in Alabama and, following his conviction in 2017, was sentenced to serve over 20 years in federal prison for violating several provisions of the federal Controlled Substances Act (CSA) relating to his prescribing practices. Dr. Ruan appealed his conviction and, in March of this year, argued before the US Supreme Court that he had been wrongfully convicted because the trial court had denied his ability to assert a good-faith defense concerning the prescriptions he issued.1 The last time the Supreme Court interpreted the CSA and its application to criminal cases involving prescribers was almost 50 years ago. The central question now before the Court is whether the government must merely prove that the prescription was issued outside of an acceptable standard of practice (limiting the focus to the prescription itself), or whether the prescriber knew that the prescription was unlawful at the time it was written (focusing on the prescriber’s intent and whether the prescriber believed in good faith that the prescription was within the standard of care).2 While we argue here that it should be the latter, the Court’s ultimate decision will establish the standard the government can use to prosecute prescribers and will affect the practice of medicine for years to come.

Evaluation of tetrahydrocannabinolic acid (THCA) synthase polymorphisms for distinguishing between marijuana and hemp.

The Controlled Substances Act (CSA) classifies marijuana (Cannabis sativa) as a Schedule I illicit drug. However, the recent Agriculture Improvement Act of 2018 (U.S. Farm Bill) removed hemp from the definition of marijuana in the CSA, making it a legal crop. As a result, many hemp products are now available, including strains of hemp buds high in other cannabinoids such as cannabidiol (CBD) or cannabigerol (CBG). The genetic inheritance of chemical phenotype (chemotype) has been widely studied, with the tetrahydrocannabinolic acid (THCA) synthase gene at the forefront. Previous studies have speculated that there are two forms of the THCA gene, one that produces an active enzyme (present in marijuana) and one that cannot produce a functional enzyme (present in hemp). A DNA analysis method is desirable for determining crop type in sample types inconducive to chemical analysis, such as immature crops, trace residues, small leaf fragments, seeds, and root material. This study optimized and evaluated a previously reported single nucleotide polymorphism (SNP) assay for determining C.sativa crop type. Furthermore, the presence or absence of 15 cannabinoids, including THC and THCA, was reported in cannabis reference materials and 15 legal hemp flower samples. The SNP assay correctly identified crop type in most samples. However, several marijuana samples were classified as hemp, and several hemp seeds were classified as marijuana. Two strains of legal CBG hemp flowers were also classified as marijuana, indicating that factors other than the genetic variation of the THCA synthase gene should be considered when determining crop type.

Kratom Abuse Potential 2021: An Updated Eight Factor Analysis.

Drugs are regulated in the United States (US) by the Controlled Substances Act (CSA) if assessment of their abuse potential, including public health risks, show such control is warranted. An evaluation via the 8 factors of the CSA provides the comprehensive assessment required for permanent listing of new chemical entities and previously uncontrolled substances. Such an assessment was published for two kratom alkaloids in 2018 that the Food and Drug Administration (FDA) have identified as candidates for CSA listing: mitragynine (MG) and 7-hydroxymitragynine (7-OH-MG) (Henningfield et al., 2018a). That assessment concluded the abuse potential of MG was within the range of many other uncontrolled substances, that there was not evidence of an imminent risk to public health, and that a Schedule I listing (the only option for substances that are not FDA approved for therapeutic use such as kratom) carried public health risks including drug overdoses by people using kratom to abstain from opioids. The purpose of this review is to provide an updated abuse potential assessment reviewing greater than 100 studies published since January 1, 2018. These include studies of abuse potential and physical dependence/withdrawal in animals; in-vitro receptor binding; assessments of potential efficacy treating pain and substance use disorders; pharmacokinetic/pharmacodynamic studies with safety-related findings; clinical studies of long-term users with various physiological endpoints; and surveys of patterns and reasons for use and associated effects including dependence and withdrawal. Findings from these studies suggest that public health is better served by assuring continued access to kratom products by consumers and researchers. Currently, Kratom alkaloids and derivatives are in development as safer and/or more effective medicines for treating pain, substances use disorders, and mood disorders. Placing kratom in the CSA via scheduling would criminalize consumers and possession, seriously impede research, and can be predicted to have serious adverse public health consequences, including potentially thousands of drug overdose deaths. Therefore, CSA listing is not recommended. Regulation to minimize risks of contaminated, adulterated, and inappropriately marketed products is recommended.

The Impact of State Drug Laws on High School Completion and College Enrollment for Latino Young Men

Although college enrollment and completion rates have increased over the past 30 years, access to higher education has not been uniform across racial groups. In addition to racial gaps, differences in tertiary education outcomes exist by gender. Gender gaps in college enrollment are larger in the Latinx community than in other racial or ethnic groups. In this paper, we use the October Current Population Survey (CPS) supplements for the years 1984–1992 and state and federal drug laws to measure the impact of the passage of the 1986 Anti-Drug Abuse Act on the likelihood of college enrollment for young Latino men. Following the passage of the federal law, some states changed their drug laws around marijuana and cocaine possession and distribution. We use this variation in state law in order to explore whether states that have more lenient marijuana and cocaine laws also have a higher likelihood of college enrollment. We find that there was a four percentage point decline in both the likelihood of high school completion and that of college enrollment for Latinx men after the passage of the 1986 Anti-Drug Abuse Act. Findings have implications for modifications to state drug laws and addressing the ways in which these laws impact educational attainment for students underrepresented in higher education.

Did the 2018 Farm Bill’s Hemp Provisions Decriminalize Marijuana?

Abstract In 2014, Congress removed industrial hemp with a concentration of ≥0.3% tetrahydrocannabinol (THC) dry weight from the definition of marijuana in the federal Controlled Substances Act (CSA). Hemp production was authorized in a limited pilot program until 2018, when Congress passed the Agricultural Improvement Act (Farm Bill) that expanded the program to anyone licensed to produce hemp by the U.S. Department of Agriculture (USDA) or by a USDA-approved State or Indian tribe. Hemp’s greatest value is in two of its 80-plus molecules: cannabidiol (CBD) and THC. These molecules, present in all forms of Cannabis sativa L. (cannabis), including hemp, have medicinal and recreational uses. By removing hemp from the CSA, the Farm Bill altered the legal status of hemp’s extracts, including CBD and THC. In 2018, Epidiolex®, the world’s first and only CBD-based medicine, was approved in the U.S. The drug was placed in Schedule V of the CSA to comply with an international drug treaty requiring control of cannabis and all its extracts. In April 2020, Epidiolex was removed from the CSA schedules. This occurred, according to the Drug Enforcement Administration (DEA), because with a THC content below 0.3%, Epidiolex no longer met the Farm Bill’s criteria as a controlled substance. This review discusses the Farm Bill’s hemp provisions and how they have affected the legal status of hemp derivatives CBD and THC. The review also discusses a loophole in the Farm Bill that decriminalizes the production of marijuana by negligent hemp farmers. In passing, we discuss how lobbying by the hemp/CBD industry influenced passage of the Farm Bill.

Waiting for a Miracle: Medical Psilocybin and Mdma under 'Right to Try'

For individuals with life-threatening, potentially incurable illnesses, surviving each day is itself a victory and simultaneously an increased chance they will live to see new, novel, potentially life-saving treatments. Unfortunately for these people, Mick Jagger’s oft chanted refrain does not ring true: time is not on their side. There exists an auspicious, and often tantalizingly elusive, period where new treatments show efficacy but remain unapproved for general use. Patients’ rights advocates have fought for—and won—new laws and regulations expanding treatment access for those most in need. “Right to Try” (RTT) laws represent one of these victories. In 2014, Colorado became the first state to pass RTT legislation. In short, RTT laws provide severely ill patients a statutory avenue permitting access to medicines in the Food and Drug Administration’s (FDA) phased trial process. Operating alongside a nearly identical FDA program called “Expanded Access,” RTT creates a “right” to access investigational drugs outside of an ongoing clinical trial. Like “Expanded Access,” RTT’s design, and limitations, single out individuals who are suffering from a life-threatening or serious illness, and who have exhausted alternative treatment options. Since 2014, forty-one state RTT laws have been enacted. In 2018, President Donald Trump signed into law the federal RTT Act, creating a national route to access experimental medicines. Roughly ten years ago, after a generation of dormancy, research institutions began applying for new authorizations to investigate substances once considered among the most promising tools in psychotherapy: psilocybin and 3,4-Methelyenedioxymethamphetamine (MDMA). Both compounds saw widespread clinical use during the 1960s, 1970s, and 1980s. Both were effectively barred from any continued study and use when each was placed on Schedule I of the Controlled Substances Act (CSA). In the psychedelic medicine renaissance of the 2010s, both psilocybin and MDMA have demonstrated unprecedented and unparalleled success treating stubborn, pervasive psychological disorders that currently contribute to the American mental health crisis: Post-Traumatic Stress Disorder (PTSD) and Major Depressive Disorder (MDD). Each substance is currently at a different stage of FDA clinical trials, and each for a different disorder: MDMA in Phase III for PTSD, and psilocybin in Phase II for MDD. A number of hurdles remain before these safe and efficacious treatments can be widely accessed. Longstanding, and problematic, legal inconsistencies account for many of these hurdles. Despite each substance having proven safety for human consumption, and no known toxicity, they both remain on the CSA’s Schedule I: reserved for substances deemed unsafe for human consumption under medical supervision. Though both substances have received national and international attention for their treatment efficacy—leading to popular ballot referendums and legislation to decriminalize these compounds on local and state levels —both remain among the most restricted substances. Most researchers and advocates have been content to wait out the long FDA trial process for rescheduling. But this process is not exclusively bound by science, and the American mental health crisis can ill afford slow-walking safe and effective treatments. This Note proposes that RTT statutes are a suitable legal avenue ensuring substances like psilocybin and MDMA reach people who are suffering, both apart from and in conjunction with the standard FDA progression. Determining this requires a comprehensive understanding of both psilocybin and MDMA’s long research histories, as well as substantive and illustrative statutory and case law analysis. Part I reviews the historical benchmarks from over a century of medical psychedelics research. Part II delves into the situationally conflicting provisions contained in the federal RTT Act of 2018 and The CSA of 1970. The RTT Act applicable to medical psilocybin and MDMA, and the CSA simultaneously barring those drugs from medical use. These two statutes, even in the context of controlled substances, are reconcilable: the CSA remaining effective for federal enforcement purposes, and RTT having enough breadth to allow therapeutic access to certain controlled substances, in this case psilocybin and MDMA. Part III analyzes two relevant Supreme Court decisions animating this Note’s fundamental legal argument. The analysis centers on two core issues addressed by the Supreme Court: deference standards for agency statutory and regulatory interpretations when promulgating interpretive rules, and the Constitutional bounds of the CSA when used as a mechanism to override state medical policies. Part IV explains the importance and urgency of the moment, and why there is value in pursuing this path towards therapeutic access. Part V proposes that the State of Vermont has a unique, achievable avenue to advance therapeutic access through modified state RTT legislation. As one of eight states to never pass a RTT law, Vermont is well positioned to introduce this legislation declaring certain treatment resistant psychological disorders “life-threatening” illnesses.

Regulating Vice: What the U.S. Marijuana Industry Can Learn From State Governance of Sports Gambling

The United States has long been a country of prohibitions, with the most memorable prohibition in American history being the ban on alcohol sales in 1920, which lasted until the ratification of the 21st Amendment to the U.S. Constitution. While the federal ban on alcohol has long since been abolished, the United States has continued to maintain the rudiments of its federal bans on both marijuana and sports betting, even though the primary beneficiaries of both of these bans has been organized criminal syndicates that have garnered near monopolies over these industries. While somewhat different from the alcohol ban of the 1920s, there are many similarities between today’s bans of both marijuana and sports betting. For instance, the U.S. Supreme Court’s decision in Murphy v. National Collegiate Athletic Association, which allowed states to legalize and regulate sports betting, catapulted the regulation of sports betting into the national spotlight, alongside marijuana. At the same time, however, there are also a few important distinctions — most notably that the federal Controlled Substances Act (CSA) classifies marijuana as a prohibited substance, whereas federal law classifies sports betting somewhat less harshly. Since the U.S. Supreme Court’s May 2018 Murphy decision, more than 35 states have introduced legislation to legalize sports betting, with 19 states successfully passing laws in the first 18 months since the Court’s Murphy decision. Likewise, medical marijuana is currently legal in 33 states, and recreational marijuana is permitted in 11 states. Nevertheless, in spite of the growing state-level legality of both marijuana and sports gambling, the exuberance for sports gambling by entities like banks and institutional investors has surpassed the marijuana industry despite the marijuana industry having a significant head start. This Article explores why sports gambling has been widely accepted and led banks and financial institutions to take risks that they have not been willing to take for the marijuana industry. It also explores best practices adopted by the sports gambling industry that the marijuana industry may be able to emulate to garner broader legal acceptance.

To CBD or not to CBD?: What pharmacists need to know

To CBD or not to CBD?: What pharmacists need to know

The Federal Judiciary’s Role in Drug Law Reform in an Era of Congressional Dysfunction

While state drug law reform is moving apace, federal drug law reform has moved much more slowly. Many, including the Judicial Conference of the United States and the United States Sentencing Commission, have urged Congress to enact substantive federal drug law reform for years. But Congress has not acted. As a result, the federal system continues to single out drug offenses for harsh treatment at the bail stage and the sentencing stage—the front end and back end of the federal mass incarceration crisis. In this paper, we argue that federal judges have a critical role to play in future federal drug law reform in light of Congress’ long-standing failures to meaningfully change the laws. At the front end, judges should encourage the release of more people on bail by closely scrutinizing prosecutors’ motions for temporary detention and giving little weight to the Bail Reform Act’s presumption of detention. Data shows that the statutory drug presumption is overbroad and does a poor job of determining who is a risk of flight or a danger to the community. At the back end, judges should issue categorical policy disagreements with the drug sentencing guidelines and the career offender sentencing guideline using the Supreme Court’s blueprint in Kimbrough v. United States. Judges should issue sentences below these guidelines because they are not based on empirical evidence, over-punish drug offenses, and result in racial disparities. At both ends, judges should rest their decisions on the evidence that the drug presumption, the drug sentencing guidelines, and the career offender sentencing guideline are flawed. While judicial action is not a cure for Congressional inaction, it would send a clear message from one co-equal branch of government to another that substantive reform is urgently needed.

DEA allows buprenorphine inductions based on telephone only

Last week, the Drug Enforcement Administration (DEA) said opioid treatment programs (OTPs) and Drug Addiction Treatment Act (DATA)–waived prescribers can treat new patients with buprenorphine based on a telephone call only. The Controlled Substances Act (CSA), enforced by the DEA, requires all new patients being treated with controlled substances to have an in‐person — or, for now, telemedicine — physical exam. Now, however, because of the coexisting COVID‐19 pandemic and opioid overdose crisis, the DEA has dropped this requirement. This follows the decision of the Substance Abuse and Mental Health Services Administration (SAMHSA) to allow exemptions from the OTP take‐home regulations allowing stable patients to be given 14 or 28 days of methadone doses, instead of coming in more frequently (see DEA, SAMHSA relax OTP/OBOT regulations due to COVID‐19, ADAW March 23, https://onlinelibrary.wiley.com/doi/10.1002/adaw.32664).

United States vs Safehouse: The implications of the Philadelphia supervised consumption facility ruling for law and social stigma

In October 2019, a federal judge ruled that a Philadelphia nonprofit (Safehouse) group's plan to open the first site in the U.S. where people can use illegal opioids under medical supervision does not violate federal Controlled Substances Act, delivering a major setback to Justice Department lawyers who launched a legal challenge to block the facility. The Judge wrote that “the ultimate goal of Safehouse's proposed operation is to reduce drug use, not facilitate it,” which represents the first legal decision about whether supervised injection sites can be legally permissible under U.S. law. Although supervised consumption facilities (“SCFs”) remain controversial, they already exist in many countries in Europe as well as Canada, Australia, and Mexico, and evaluations of their public health impact have demonstrated the value of this practice. The decision is hailed as a public health victory and could shape the legal debate in other U.S. cities. Challenges remain as stigmatizing attitudes regarding substance use are widely accepted, culturally endorsed, and enshrined in policy. The Safehouse case shows that SCFs might be able to survive under current federal drug laws, but public understanding and support of these facilities will also be crucial for cities and states to open them.

Legal and Regulatory Issues Governing Cannabis and Cannabis-Derived Products in the United States.

This chapter provides an in-depth discussion of the legal and regulatory frameworks surrounding cannabis in the United States, including federal law—as dictated by the Controlled Substances Act (CSA) and governed by various federal agencies like the FDA and DEA—as well as state law—as regulated by each state’s laws and regulations authorizing medical and/or adult use cannabis. First, the chapter discusses the definition and classification of cannabis under the CSA, including scheduling under the CSA as well as the process for and potentiality of removing cannabis from Schedule I. Then, it describes the activities relating to industrial hemp that are permitted under the 2014 and 2018 Farm Bill. Next, the chapter addresses state-level cannabis laws. The chapter also analyzes the question of whether state cannabis laws are invalidated and superseded by federal law. Moreover, this section examines the factors underlying the extent of the Department of Justice’s enforcement actions relating to state-authorized cannabis activities. The chapter then turns to CBD (cannabidiol) in particular, discussing CBD’s legal status under the CSA; the FDA’s role in regulating and approving CBD products for medical purposes; and the steps required to take an investigational CBD product through that approval process. The chapter concludes by contending that, while cannabis has had a long and twisting history, and although cannabis-derived products face daunting obstacles to achieving FDA approval as well as rescheduling under both federal and state law, the recent success of one product (Epidiolex®) should inspire other manufacturers to develop additional cannabis-derived products through the FDA process.

Assessing the Structural and Pharmacological Similarity of Newly Identified Drugs of Abuse to Controlled Substances Using Public Health Assessment via Structural Evaluation.

The US Food and Drug Administration's Center for Drug Evaluation and Research (CDER) developed an investigational Public Health Assessment via Structural Evaluation (PHASE) methodology to provide a structure‐based evaluation of a newly identified opioid's risk to public safety. PHASE utilizes molecular structure to predict biological function. First, a similarity metric quantifies the structural similarity of a new drug relative to drugs currently controlled in the Controlled Substances Act (CSA). Next, software predictions provide the primary and secondary biological targets of the new drug. Finally, molecular docking estimates the binding affinity at the identified biological targets. The multicomponent computational approach coupled with expert review provides a rapid, systematic evaluation of a new drug in the absence of in vitro or in vivo data. The information provided by PHASE has the potential to inform law enforcement agencies with vital information regarding newly emerging illicit opioids.

Scheduling synthetic cathinone substances under the Controlled Substances Act.

Cathinones are amphetamine analogues that produce stimulant effects with rewarding properties. For many decades, synthetic cathinones have been used in the United States (USA) for abuse purposes, leading to concern about public safety by the federal government. Under the Controlled Substances Act (CSA), the federal government may place drugs with high abuse potential but no currently accepted medical use into Schedule I of the CSA. The process of scheduling an abusable drug involves both the Department of Health and Human Services (HHS), through the Food and Drug Administration (FDA) and the National Institute on Drug Abuse (NIDA), and the Department of Justice, through the Drug Enforcement Administration (DEA). This paper details how numerous synthetic cathinones were placed under CSA control between 1973 and 2018, with an emphasis on 10 cathinones that were placed into Schedule I in 2017 (butylone, naphyrone, pentylone, pentedrone, 3-fluoro-N-methylcathinone (FMC), 4-FMC, 4-methyl-N-ethylcathinone, 4-methyl-pyrrolidinopropiophenone, alpha-pyrrolidinobutiophenone, and α-pyrrolidinopentiophenone). A summary is provided of the scientific and medical analysis performed by HHS, in the form of an Eight-Factor Analysis (8FA), as prescribed by the CSA. This 8FA was then evaluated and signed by the Assistant Secretary for Health at HHS and transmitted to DEA, which permanently placed the 10 cathinones into Schedule I after public notices were published into the Federal Register. Understanding the scientific data, analysis, and complex process utilized by the US federal government in the CSA scheduling of cathinones with abuse potential and no accepted medical use is important for transparency in governmental decision-making.