Introduction Since the 1960s, Congress has passed measures to authorize and fund international family planning related activities that give partici pants access to a broad range of contraceptive methods and services. Such assistance is intended to support broader U.S. international development priorities, as stated in Section 104 of the Foreign Assistance Act of 1961, as amended (P.L. 87-195): The Congress recognizes that poor health conditions and uncontrolled population growth can vitiate otherwise successful development efforts. Large families in developing countries are the result of complex social and economic factors which change relatively slowly among the poor majority least affected by economic progress, as well as the result of a lack of effective birth control. Therefore, effective family planning depends upon economic and social change as well as the delivery of services and is often a matter of political and religious sensitivity. While every country has the right to determine its own policies with respect to population growth, voluntary population planning programs can make a substantial contribution to economic development, higher living standards, and improved health and nutrition. Section 104 goes on to authorize U.S. assistance to address the impact of population growth on development through family planning activities: In order to increase the opportunities and motivation for family planning and to reduce the rate of population growth, the President is authorized to furnish assistance, on such terms and conditions as he may determine, for voluntary population planning. In addition to the provision of family planning information and services, including also information and services which relate to and support natural family planning methods, and the conduct of directly relevant demographic research, population planning programs shall emphasize motivation for small families. According to the U.S. Agency for International Development (USAID), the primary federal agency charged with administering development assistance, family planning refers to "services, policies, information, attitudes, practices, and commodities, including contraceptives, that give women, men, couples, and adolescents the ability to avoid unintended pregnancy and choose whether and/or when to have a child." Over time, family planning programs evolved beyond a strict focus on contraception to provide information and services on a wide range of issues that adversely affect sexual and reproductive health (e.g., female genital mutilation and cutting (FGM/C), obstetric fistula, and gender based violence (GBV)). This broader scope is reflected in the common categorization of these activities as reproductive health/family planning (RH/FP) assistance. Reproductive health refers to "all matters relating to the reproductive processes, functions, and system at all stages of life." The United States is the largest country donor to international FP/RH programs, providing $575 million dollars annually in recent years. Although U.S. funding for FP/RH activities has been consistent for years, the programs remain a subject of intense congressional debate. While the law explicitly prohibits the use of funds to provide abortion or involuntary sterilization, some Members of Congress continue to express concern that FP/RH may indirectly support such activities as a result of funding fungibility. Other concerns relate to the cultural appropriateness of family planning activities and the relationship between FP/RH and broader global health and development assistance. This report focuses on the scope and intended impact of U.S. bilateral international family planning programs administered by USAID. It does not comprehensively address related legislative restrictions (although a table listing such restrictions is provided in the Appendix), or discuss aid channeled through multilateral organizations, such as the U.N. Population Fund (UNFPA). Family Planning: Key Issues International FP/RH programs aim to provide women with the information and services needed to make informed decisions regarding their contraceptive options and to ensure healthy reproductive systems and safe pregnancies. According to USAID, a key aspect of these programs is family planning, as some 885 million women worldwide would like to avoid or delay pregnancy. Of those women, 212.4 million (24%) lack access to FP/RH services. Supporters of FP/RH programs assert that access to such services is necessary for safe motherhood. They cite evidence that bearing children too close together, too early, or too late in life can threaten the health of the mother and her baby. In addition, lack of access to family planning services can have negative social and economic impacts that undermine broader global development goals. For example, some experts note that improving access to family planning services has been shown to have benefits for children's health, women's empowerment, and sustainable growth and development. Critics of international family planning programming have expressed concern that despite existing restrictions, U.S. dollars could be used indirectly to support abortion or involuntary sterilization if implementing partners use U.S. funds for approved services, freeing up funding from other sources to support abortion or involuntary sterilization. Other detractors argue that U.S. foreign assistance for contraceptive provision is an inappropriate imposition on local cultural or religious norms, further asserting that abstinence education is a more effective form of family planning. Critics have also questioned the practice of allocating specific resources for FP/RH programs rather than allocating aid to broader women's health programs or for other development priorities that they argue would be a more effective use of U.S. funds. Evolution of U.S. Policy and Programs Since U.S. bilateral FP/RH programs and policies were launched in 1965, they have evolved to reflect changes in global health priorities and emphasize the link between development and gender. The Foreign Assistance Act of 1961 (P.L. 87-195; as amended) first authorized research on family planning issues, among many other things, and in 1965 Congress authorized USAID to create contraceptive distribution programs through the Office of Population. Initial programs focused on procuring contraceptive supplies for distribution in developing countries. At the time, the rationale for these programs was that high birth rates "significantly increase the cost and difficulty of achieving basic development objectives by imposing burdens on economies presently unable to provide sufficient goods and services for the growing population." From the 1970s through the 1990s, USAID expanded international family planning assistance to include programs on fertility, reproductive and women's health, and maternal and child health, ultimately reorganizing the program into an Office of Population and Reproductive Health (PRH). The expansion of activities reflected changing attitudes and development strategies. Concerns about managing population growth were largely supplanted by a focus on advancing women's status and enhancing their individual health and empowerment. USAID family planning activities continued to utilize a multipronged approach, entailing the provision of contraception while also addressing broader reproductive health concerns. USAID Priorities and Key Programs USAID's FP/RH programs are administered through the Office of Population and Reproductive Health (PRH) within the agency's Global Health Bureau. PRH is responsible for setting technical and programmatic direction, providing technical leadership, and supporting field programming. USAID distributes FP/RH commodities (such as contraceptives) and related services primarily through contracts and grant agreements with nongovernmental organizations. The agency's technical and administrative staff oversee and monitor the work of implementing partners. USAID FP/RH programming is organized around six priorities: 1. Supporting healthy timing and spacing of pregnancy. 2. Advancing community-based delivery of FP/RH services, such as deploying front-line community health workers to disseminate commodities and information, and to arrange referrals. 3. Ensuring adequate supplies of contraceptives. 4. Providing non-coerced access to surgical sterilization and long-acting reversible contraceptives (LARCS), such as intrauterine devices and contraceptive implants. 5. Integrating FP/RH and HIV/AIDS programs to ensure that HIV-positive men and women have access to family planning information and services, for disease prevention and to prevent mother-to-child transmission of the virus. 6. Integrating FP/RH and maternal and child health (MCH) programs, specifically during the postpartum period, when there is considerable demand from new mothers for contraception to ensure pregnancy spacing. In addition to these priorities, USAID FP/RH programs may also focus on related policy areas, such as efforts to end child marriage, female genital mutilation and cutting, and gender-based violence; and related health goals, including the prevention of fistula. Programs and Activities USAID works with implementing partners to fund programs and provide technical assistance for the following family planning and reproductive health programs and activities: D elivery of FP/RH services . Examples include providing women with counseling to promote awareness of available contraceptives or other methods of birth control, or procedures at health facilities to insert Intrauterine Devices (IUDs) or other forms of Long Acting Reversible Contraceptives (LARCs). Contraceptive supply and logistics âimplementation and management of supply chains for contraceptives, including condoms. In FY2018, for example, USAID donated 28 million male condoms to developing countries through the agency's implementing partners. Biomedical and social science research âthe study of biomedical and social science evidence to identify best practices in programming and implementing family planning services. For example, USAID created Demographic and Health Surveys (DHS) and partnered with national governments and implementing partners to use the tool for conducting household- and facility-based surveys on health attitudes and behaviors in Africa, Asia, Latin America, the Caribbean, and Eastern Europe. In addition, USAID provides direct technical assistance to foreign ministries of health and other partners, focusing on the following areas: Performance and quality improvement âthe use of data to improve both access to FP/RH services and their quality. For example, data from USAID-supported surveys are used to analyze women's use of family planning methods (e.g., effectiveness of contraceptive method, provider attitudes towards patients, or provider-patient interactions). Health communication âthe use of mass media, community-level, and interpersonal communication strategies to expand knowledge of contraception, healthy approaches to birth spacing, and sex education, as well as awareness and prevention of GBV, forced early and child marriage (FECM), and FGM/C. For example, USAID supports community health promoters and behavior change campaigns, to educate women and their families on a variety of issues such as access to reproductive health services, the importance of maternal and neonatal health provider check-ups, and the health and psychosocial risks of FGM/C to women and girls. Policy analysis and planning âsupport for the development, implementation, and monitoring of policies and laws that affect FP/RH policies and programs, and women's health outcomes. For example, USAID supported a research project in Kenya which analyzed the country's evolving health policies (e.g., the National Population Policy for National Development and the Adolescent Reproductive Health and Development Policy) and contraceptive distribution programs, to evaluate impact on Kenya's total fertility rate and contraceptive prevalence rate. Monitoring and evaluation (M&E) âthe evaluation of programs to understand the content, quantity, and potential effects of services being provided with U.S. government assistance. Integration of FP/RH and MCH activities â According to USAID, access to family planning services can prevent 30% of maternal deaths (or approximately 90,000 deaths annually). USAID implementing partners often provide integrated FP/RH and MCH services, where appropriate. Many experts recognize MCH programs as a natural entry point for promoting awareness of and access to family planning services, as in the post-natal period evidence suggests that women have an increased desire to plan or prevent future pregnancies. For example, a mother bringing her child to a routine vaccination appointment might also be able to receive maternal health services and counseling on contraceptive options. Fourteen USAID-supported countries highlight integration of FP/RH and MCH as an approach to community health service delivery in their national government policies. However, USAID MCH programs are funded separately from FP/RH programs, as there are also FP/RH programs that focus on issues outside the realm of MCH (e.g., programs addressing adolescent sexual and reproductive health, prevention of FECM, GBV, FGM/C and obstetric fistula). In India, for example, USAID FP/RH funds supported programs to provide counseling and referral of GBV survivors to service providers, such as psychosocial counselors. Countries Receiving USAID FP/RH Assistance In 2018, USAID supported bilateral family planning and reproductive health aid programs in more than 40 countries, including 24 "priority" countries, which are the focus of FP/RH programs and technical assistance and receive the majority of FP/RH funding. Most of these priority countries (23 of 24) are also categorized as MCH priority countries by USAID. To determine priority status, USAID evaluates which countries have the highest need, based on the magnitude and severity of their neonatal and maternal death rates; demonstrated national commitment to achieving sustainable and efficient program outcomes; and the greatest potential to leverage U.S. government support. USAID FP/RH priority countries are largely in Africa ( Figure 1 ). Compared with other developing nations and regions, Africa has the highest concentration of countries with low rates of modern contraceptive use and highest maternal mortality rates ( Table B-1 ). In 2018, the top three recipients of U.S. FP/RH assistance were Nigeria ($37 million), Uganda ($29 million), and Tanzania ($28 million). In 2018, USAID provided $2 million or less (per country) annually to support FP/RH programs in an additional 18 countries that were assessed to have a need for family planning services (e.g., Benin), and/or a strategic foreign policy interest to the United States (see Table B-2 ). For example, despite relatively low fertility and maternal death rates, Ukraine receives USAID FP/RH funds as part of a multifaceted approach to supporting Ukraine as a free and democratic state "in the face of continued Russian aggression." Criteria for Country "Graduation" USAID formalized a country graduation process for FP/RH assistance in 2006, to transition countries off of U.S. foreign assistance for FP/RH programs and prioritize countries when allocating funding. The graduation strategy also aligns with the agency's "Journey to Self-Reliance," a policy framework established in 2018 to strengthen the ability of partner countries to support their own development agendas. Countries receiving family planning assistance may "graduate" once they have met certain criteria and a country program has achieved its stated goals. According to USAID, a country is eligible for graduation once it reaches a modern contraceptive prevalence rate of at least 51%; and reaches a level of fertility at or below 3.1 children per woman. USAID also considers additional issues when evaluating a country's readiness for graduation. Countries who reach both criteria but lack the capacity to implement family planning programs or face other constraints may continue to receive assistance (e.g., India). USAID may also evaluate whether governments are allocating sufficient public funds for contraception procurement and whether their Ministries of Health demonstrate adequate capacity to manage the associated logistics and supply chain processes. Additional indicators considered for graduation include at least 80% of the population can access at least three methods of FP; no more than 20% of FP products, services and programs offered in the public and private sectors are subsidized by USAID; and major service providers in all sectors (public, non-governmental, commercial) can meet and maintain standards of informed choice and quality of care. To date, USAID 25 countries have graduated, half of which are in Latin America and the Caribbean ( Table B-4 ). For example, Brazil graduated in 2000, after the government, non-governmental organizations, and the private sector invested substantially in family planning assistance, and as the country's Gross Domestic Product (GDP) increased. USAID partners worked to build capacity in Brazil's civil sector and Ministry of Health programs, by focusing on outreach, education, and improved access to care. According to USAID, "the program worked with the government to reduce Brazil's legal obstacles and tariff barriers to the importation of medical equipment, foam, jellies, and oral contraceptives, as well as quality intrauterine devices and condoms not manufactured in Brazil." Perhaps reflecting these efforts, Brazil's contraceptive prevalence rate increased from 34% in 1970, to 72% in 2000. Other countries who were graduated (e.g., Mexico), demonstrated similar characteristics. Once a country graduates, PRH evaluates where U.S. resources can best be reallocated based on need. In 2011, for example, USAID formed the Ouagadougou Partnership (named for the capital of Burkina Faso) with funding reallocated from graduated Latin American countries. This partnershipâwhich also involves the government of France, the Bill and Melinda Gates Foundation, and the Hewlett Foundationâseeks to improve access to family planning services in francophone West Africa. ( Table B-3 ). U.S. Funding Bilateral FP/RH assistance is funded through a variety of accounts in annual Department of State, Foreign Operations, and Related Programs (SFOPS) appropriations measures. The Global Health Programs (GHP) account is the funding channel for more than 90% of bilateral FP/RH aid while smaller amounts of bilateral FP/RH assistance are generally made available through other accounts. Department of State Economic Support Fund (ESF) monies are provided to select countries considered by the State Department to be politically and strategically important. In recent years, Pakistan, Afghanistan, and Jordan have received ESF funds for FP/RH activities. In FY2017, for example, Afghanistan, which is a USAID FP/RH priority country, received $20 million in bilateral family planning assistance, all of which was provided through the ESF. Over the past decade, enacted funding levels for bilateral international FP/RH aid have remained fairly consistent ( Figure 2 ). Although congressionally enacted funding has been constant since 2011, the absence of foreign assistance authorization legislation in recent decades has made annual consideration of foreign aid appropriations the primary venue for debating international family planning and reproductive health policy. Controversies that are frequently debated as part of the appropriations process include codification of the Mexico City Policy/Protecting Life in Global Health Assistance (MCP/PLGLHA), which is currently imposed through Executive Order (see "Selected Issues for Congress"); the effect that withholding U.S. dollars as a result of such restrictions could have on access to voluntary family planning and other health services in developing countries; and whether or not designating funding for contraceptive provision and family planning is the best approach to allocating global health funds. Members of Congress hold varied perspectives on these issues. Some Members have supported expanding access to FP/RH services, while others aim to increase restrictions on such services or reduce funding levels. in addition to these perennial concerns, debate in the 116 th Congress regarding FP/RH programs has addressed issues such as the role of faith-based contractors in USAID FP/RH programs, bias and discrimination against potential aid recipients, and language around sexual and reproductive health. In recent years, controversy has also arisen over how FP/RH services are described in government documents, though it remains unclear whether language changes have had any impact on actual service provision. Selected Issues for Congress When considering U.S. support for international family planning and reproductive health efforts, the 116 th Congress may focus on three key areas: restrictions under the MCP/PLGHA, funding levels in appropriations bills, and program reforms proposed in pending legislation. Mexico City Policy/PLGHA The Mexico City Policy requires foreign nongovernmental organizations receiving USAID family planning assistance to certify that they will not perform or actively promote abortion as a method of family planning, even if such activities are conducted with non-U.S. funds. Since first applied in the Reagan Administration in 1984, the policy has been repeatedly lifted and reinstated through Executive Order. The policy was maintained by President George H.W. Bush and rescinded by President Clinton in 1993. It was then reinstated by President George W. Bush in 2001, who expanded the policy in 2003. President Obama rescinded the policy upon taking office in January 2009. The Trump Administration reinstated the policy, expanded it to include all U.S. global health assistance, and renamed it Protecting Life in Global Health Assistance (PLGHA). The Trump Administration uses the two policy names interchangeably, though the Mexico City Policy until now only applied to international family planning and reproductive health programs. When discussing the policy under the Trump Administration, this report uses MCP/PLGHA. MCP/PLGHA has never been enacted through legislation, and advocates have long encouraged Congress to codify the policy, making it harder for future Administrations to revoke. Simultaneously, detractors of the policy have called for enactment of legislation that would prevent the current practice of Administrations imposing the policy through Executive Order. Some international FP/RH program advocates suggest there are issues and confusion regarding compliance with the expansion of MCP to include all global health assistance. They assert that the policy has rendered programs cumbersome and ineffective due to administrative and operational burdens associated with ensuring compliance, which divert resources from the health workforce, health information systems, and service delivery. Some field reports indicate that individual providers may not be aware of the restrictions because MCP/PLGHA is "embedded" in funding agreements, similar to "fine print," which can create barriers to care during a provider-patient interaction. Advocates of the expanded policy argue that it closes loopholes in the prior policy and does not cause an undue burden, asserting that the government must focus on compliance. In February 2018, the State Department released the findings of a six-month review of MCP/PLGHA. The State Department acknowledged the confusion the policy created, stated that the policy's impact on program effectiveness was minimal, and committed to conduct another review at the end of 2018. As of February 2020, the State Department had not announced plans for a second review. Congress could choose to mandate completion of the second review through legislation or examine the situation through oversight activities. Setting Funding Levels for International FP/RH Programs In recent years, congressional debates regarding international FP/RH assistance have centered on where and how such funding should be spent. For FY2020, Congress appropriated $575 million to international family planning programs. Some advocates have argued that global FP/RH funding levels would need to be doubled in order to make family planning and reproductive services accessible to all women who currently want and lack access to them. Proponents say that consistently flat funding is equivalent to FP/RH spending cuts, and this undermines U.S. global development goals on maternal and child health. Advocates note that the U.S. government would need to invest $1.5 billion to meet its appropriate share of the burden for foreign assistance for FP/RH funding, and other donor countries cannot fill the gap. Opponents of the aid have questioned the extent of international demand for family planning services and have suggested that international family planning resources could be better used on other development activities. Further, opponents argue that international family planning services are controversial in some countries due to religious and moral beliefs, which, in their views, raises questions about whether increased donor funding would lead to increased use of contraceptives and reproductive health care services or to better maternal health outcomes. Some observers also question whether the programs have been efficient and cost-effective, given the scale of U.S. spending on bilateral family planning programs, compared to other types of U.S. assistance. While data appears to show positive program impact in some countries, the attribution of results specifically to U.S. programming can be debated given the many factors that influence contraceptive use, including social and economic change and the activities of other international donors. In this context, Congress may consider whether funding levels for bilateral international family planning assistance align with need and potential impact, as well as with U.S. strategic goals and foreign policy objectives. Formal Integration of FP/RH and MCH Programs and FundingÂ Streams Currently, though some U.S. international FP/RH and MCH programs may be integrated (e.g., both types of health services are provided together), most are not, due in part to separate line item funding in the annual Department of State, Foreign Operations, and Related Programs appropriations measures, separate funding entails separate program administration. Proponents of further program integration want to combine FP/RH and MCH services; they note that integration of these services has been shown to increase women's use of contraception, improve maternal health outcomes, and build health systems capacity. Integration of these funding streams may also provide more flexibility to implementing agencies to prioritize funding across a broader range of programs. On the other hand, eliminating funding directives specific to FP/RH and MCH may also reduce congressional control over how funds are used. Furthermore, opponents note that respect for local cultural norms must be considered; in some contexts, service integration could be detrimental to MCH activities if they are associated with less socially acceptable family planning programs. Aid-recipient countries may also resist integration of these programs when separate government health units administer international FP/RH and MCH services and may fear losing prioritization and resources. Others have also raised concerns that embedding FP/RH programs in MCH services would limit USAID programs to address adolescent sexual and reproductive health, and prevent CEFM, GBV, and obstetric fistula - that are distinct from family planning. Congress may consider whether formally integrating FP/RH and MCH funding streams would be beneficial to program efficacy, or if existing appropriations and implementation mechanisms best further the stated objectives of U.S. international FP/RH and MCH programs. Pending Legislation In addition to appropriations legislation, a few proposals specific to international FP/RH are pending in the 116 th Congress: H.R. 661 , the Protecting Life in Global Health Assistance Act of 2019, which would amend the Foreign Assistance Act of 1961 (22 U.S.C. 2351). This legislation was introduced to codify the Trump Administration's expansion of the Mexico City Policy to include all global health assistance. It would "prohibit U.S. assistance to foreign nonprofits, nongovernmental organizations, or quasi-autonomous organizations that promote or perform abortions, except in cases of rape or incest or where the mother's life is endangered." H.R. 1581 , the Reproductive Rights are Human Rights Act of 2019, and S. 707 , the corresponding Senate bill, would amend the Foreign Assistance Act of 1961 (22 U.S.C. 2351) to "include in its annual reports on human rights in countries receiving U.S. development and security assistance a discussion of the status of reproductive rights in each country, including whether a country has adopted and enforced policies to: (1) promote access to contraception and accurate family planning information, (2) provide services to ensure safe and healthy pregnancy and childbirth, (3) expand or restrict access to safe abortion services, (4) prevent maternal deaths, and (5) prevent and treat sexually transmitted diseases." The bills would also require the reports to include data on maternal deaths and discrimination and violence against women and girls in health care settings, including the government's response to these actions. Appendix A. Restrictions on U.S. Funding for Voluntary FP/RH Programs Appendix B. USAID FP/RH Priority Countries: KeyÂ Statistics, 2017


Background Cannabidiol (CBD) , a compound in the Cannabis sativa plant , has been promoted as a treatment for a range of conditions, including epileptic seizures, post-traumatic stress disorder, anxiety, inflammation, and sleeplessness . However, limited scientific evidence exists to substantiate or disprove the efficacy of CBD in treating these conditions . In the United States, CBD is being marketed in food and beverages, dietary supplements, cosmetics , and tobacco products such as electronic nicotine delivery systems (ENDS , the overarching term encompassing electronic cigarettes) âproducts that are primarily regulated by the Food and Drug Administration (FDA) under the Federal Food, Drug, and Cosmetic Act (FFDCA). CBD is also the active ingredient in Epidiolex , an FDA-approved pharmaceutical drug used to treat seizures associated with two rare and severe forms of epilepsy . CBD is derived from the Cannabis sativa plant (commonly referred to as cannabis), which includes both hemp and marijuana (defined further below). CBD and tetrahydrocannabinol (THC) are thought to be the most abundant cannabinoids in the cannabis plant and are among the most researched cannabinoids for their potential medical value. THCâa psychoactive compoundâis found at high levels in m arijuana and low levels in hemp (see Figure 1 ). CBD, on the other hand, is generally considered to be nonpsychoactive and may be derived from either hemp or marijuana. As described below, this distinction is relevant for purposes of oversight by the Drug Enforcement Administration (DEA), but generally not for FDA oversight. FDA has stated that it "treats products containing cannabis or cannabis-derived compounds as it does any other FDA-regulated productsâmeaning they're subject to the same authorities and requirements as FDA-regulated products containing any other [non-cannabis] substance. This is true regardless of whether the cannabis or cannabis-derived compounds are classified as hemp under [7 U.S.C. Section 1639o] as amended by the 2018 [f]arm [b]ill." In contrast, the DEA does not regulate cannabis or cannabis-derived compounds that meet the statutory definition of hemp. Botanically, marijuana and hemp are from the same species of plant, Cannabis sativa , but from different varieties or cultivars. Marijuana and hemp have separate definitions in U.S. law and are subject to different statutory and regulatory requirements. M arijuana (as defined in statute) generally refers to the cultivated plant used as a psychotropic drug, either for medicinal or recreational purposes. Marijuana is a Schedule I controlled substance under the Controlled Substances Act (CSA) and is regulated by DEA. Schedule I substances are subject to the most severe CSA restrictions and penalties; with exceptions for federally approved research, it is a federal crime to grow, sell, or possess the drug. Thus, under the CSA, the unauthorized manufacture, distribution, dispensation, and possession of marijuana and its derivatives (including marijuana-derived CBD) are prohibited. Hemp (as defined in statute separately from marijuana), on the other hand, may be legally cultivated under federal law, subject to oversight by the U.S. Department of Agriculture (USDA). Hemp is generally grown for use in the production of a wide range of products, including foods and beverages, personal care products, dietary supplements, fabrics and textiles, paper, construction materials, and other manufactured and industrial goods (see Figure 2 ). Until December 2018, hemp was included in the CSA definition of marijuana and was thus subject to the same restrictions as marijuana. The Agriculture Improvement Act of 2018 (2018 farm bill; P.L. 115-334 ) removed hemp and its derivatives (including hemp-derived CBD) from the CSA definition of marijuana. As a result, hemp is no longer subject to regulation and oversight as a controlled substance by DEA. Instead, hemp production is now subject to regulation and oversight as an agricultural commodity by USDA. CBD and CBD-related products that do not meet the statutory definition of hemp (in 7 U.S.C. Â§1639o) continue to be prohibited (aside from lawful use for research purposes) under the CSA and remain regulated by DEA. Changes enacted in the 2018 farm bill related to hemp were expected by many to generate additional market opportunities for hemp-derived consumer products such as hemp-derived CBD. However, the farm bill also explicitly preserved FDA's authorities under the FFDCA and Section 351 of the Public Health Service Act, including for hemp-derived products. As mentioned above, cannabis and cannabis-derived FDA-regulated products are subject to the same authorities and requirements as FDA-regulated productsâincluding pharmaceutical drugs, food, dietary supplements, and cosmeticsâcontaining any other substance (whether cannabis-derived or otherwise). As described below, FDA has determined that it is unlawful to introduce food containing added CBD into interstate commerce, or to market CBD as or in dietary supplements. FDA has not made similar determinations for other FDA-regulated product categories (pharmaceutical drugs, cosmetics, and tobacco products). FDA Regulation of CBD Products In the United States, CBD is the active ingredient in the prescription drug Epidiolex. CBD is also being marketed in food and beverages, dietary supplements, cosmetics, and tobacco products such as ENDS. Each of these product types is governed by different statutory and regulatory requirements, primarily administered by FDA. The agency also shares regulatory authority with other entities; for example, the Alcohol and Tobacco Tax and Trade Bureau (TTB), with regard to alcoholic beverages, and the Federal Trade Commission (FTC), with regard to the advertising and promotion of certain CBD products. This section provides an overview of how FDA regulates drugs, food, dietary supplements, cosmetics, and tobacco products, and the applicability of those requirements to products that contain CBD. Table 1 summarizes selected regulatory requirements by CBD product type. Pharmaceutical Drugs FDA, under the FFDCA, regulates the safety and effectiveness of prescription and nonprescription (over-the-counter, or OTC) drugs sold in the United States. Prescription drugs require health practitioner supervision to be considered safe for useâdue to drug toxicity, potential harmful effect, or method of useâand may be dispensed only pursuant to a prescription. In contrast, OTC drugs may be used without a prescriber's authorization, provided they have an acceptable safety margin, low potential for misuse or abuse, and are adequately labeled so that consumers can self-diagnose the condition, self-select the medication, and self-manage the condition. The statutory definition of the term drug includes "articles (other than food) intended to affect the structure or any function of the body of man or other animals" and "articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals." In general, a new drug may not be introduced into interstate commerce without FDA approval. For purposes of new drug approval, except under very limited circumstances, FDA requires data from clinical trials to provide evidence of a drug's safety and effectiveness. Before testing in humansâcalled clinical testingâthe drug's sponsor (usually its manufacturer) must file an investigational new drug (IND) application with FDA. Once a manufacturer completes clinical trials, it submits the results of those investigations, along with other information, to FDA in a new drug application (NDA). In reviewing an NDA, FDA considers whether the drug is safe and effective for its intended use; whether the proposed labeling is appropriate; and whether the methods used to manufacture the drug and the controls used to maintain the drug's quality are adequate to preserve the drug's identity, strength, quality, and purity. The NDA process can be used to obtain approval of both prescription and OTC drugs. If a sponsor wants to transfer an approved drug from prescription to OTC status (called an Rx-to-OTC switch), the sponsor must submit to FDA an NDA (or a supplement to an NDA) providing data to support the switch. As part of an NDA for an OTC drug, FDA may require the sponsor to conduct label comprehension studies assessing the extent to which consumers understand the information in the proposed labeling. FDA also may recommend that the sponsor conduct self-selection studies to assess whether consumers can appropriately self-select a drug based on the information on the labeling. In June 2018, FDA approved an NDA for the prescription drug Epidiolex, submitted by GW Pharmaceuticals, for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome in patients two years old and older. The active ingredient in Epidiolex is CBD, although its mechanism of actionâthat is, the mechanism by which it exerts its anticonvulsant effectsâis not known. FDA approved Epidiolex in June 2018; at that time, the drug contained a chemical constituent of marijuana (CBD) that was considered a Schedule I controlled substance. Therefore, it could not be marketed unless rescheduled by the DEA. Upon FDA approval, Epidiolex no longer met the criteria for placement in Schedule I, as it now had an accepted medical use in the United States. On September 28, 2018, based on a recommendation from FDA, DEA issued an order placing FDA-approved drugs that contain cannabis-derived CBD and no more than 0.1% THC in Schedule V. Epidiolex is available by prescription and only at specialty pharmacies. It is the first (and only) pharmaceutical formulation of highly purified, plant-derived CBD available in the United States. Because Epidiolex is designated as an orphan drug (i.e., a drug that treats a rare disease or condition), it was awarded seven years of marketing exclusivity upon approval. This means that FDA cannot approve an NDA for the same drugâin this case, one that has CBD as its active ingredientâfor the same disease or condition (i.e., for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients two years old and older) for seven years, with limited exceptions. Foods and Food Additives The FFDCA defines food to mean "(1) articles used for food or drink for man or other animals, (2) chewing gum, and (3) articles used for components of any such article." FDA's Center for Food Safety and Applied Nutrition (CFSAN) is responsible for oversight of human food, while FDA's Center for Veterinary Medicine (CVM) is responsible for oversight of animal food (feed). The FFDCA requires that all human and animal foods are safe to eat, produced in compliance with current good manufacturing practices (CGMPS), contain no harmful substances, and are truthfully labeled, among other things. Generally, food intended for human or animal consumption is not approved by FDA prior to marketing. However, any substance added to food is a food additive, subject to premarket review and approval by FDA. An exception to this is if a substance is generally recognized as safe (i.e., GRAS) under the conditions of its intended use, among qualified experts, or unless the use of the substance is otherwise excepted from the definition of a food additive. To obtain approval of a substance as a food additive, a person may submit to FDA a food additive petition, which proposes the issuance of a regulation prescribing the conditions under which the additive may be safely used. Food additives are approved for specific uses (e.g., to improve taste, texture, or appearance; to improve or maintain nutritional value; or to maintain or improve safety and freshness). If FDA determines, after reviewing the data submitted in a petition, that a proposed use of a food additive is safe, the agency issues a regulation authorizing that specific use of the substance. The use of a food substance may be determined to be GRAS either through scientific procedures or, for a substance used in food before 1958, through scientific procedures or experience based on common use in food. FDA established a voluntary GRAS notification process that permits any person to notify the agency of a conclusion that a substance is GRAS under the conditions of its intended use in human food. A substance is considered GRAS on the basis of common knowledge about its safety for its intended use, and the data and information relied upon for the GRAS substance must be generally available . This is in contrast to the data and information used to support a food additive petition, which are generally privately held and submitted to FDA for evaluation. Additional information about the food additive petition process and submission of GRAS notifications is available in Appendix A . Under the FFDCA, it is unlawful to introduce into interstate commerce a food (human or animal) to which a drug has been addedâeither an approved drug or a drug for which substantial clinical investigations have been instituted and made public. There are several exceptions to this: (1) if the drug was marketed in food before it was approved as a drug or before clinical drug investigations were instituted; (2) if the Secretary has issued a regulation, after notice and comment, approving the use of such drug in the food; (3) if the use of the drug in the food is to enhance the safety of the food and not to have independent biological or therapeutic effects on humans, and the use is in conformity with specified requirements; or (4) if the drug is a new animal drug whose use is not unsafe under FFDCA Section 512. FDA has concluded, based on available evidence, that none of these are the case for CBD, and because CBD is an active ingredient in an approved drug, FDA has taken the position that it is unlawful to introduce into interstate commerce food containing added CBD (i.e., to use CBD as a food additive). However, according to FDA, cannabis-derived ingredients that do not contain CBD (or THC) may fall outside the scope of this prohibition. Foods containing parts of the hemp plant that include only trace amounts of CBD (e.g., hemp seed and ingredients derived from hemp seed) may be lawfully marketed under certain circumstancesâpursuant to FDA approval as a food additive or a GRAS determination. In December 2018, FDA announced that it had completed its evaluation of three GRAS notices related to hemp seed-derived ingredients (i.e., hulled hemp seeds, hemp seed protein, and hemp seed oil). FDA had no questions regarding the company's conclusion that the use of such products as described in the notices is safe. Thus, FDA allowed them to be marketed in human foodsâwithout food additive approvalâfor the uses specified in the GRAS notices, provided they comply with all other applicable requirements. Intended uses of the hemp seed-derived ingredients include adding them as a source of protein, carbohydrates, oil, and other nutrients to beverages (e.g., smoothies, protein drinks, and plant-based alternatives to dairy products), as well as to soups, dressings, baked goods, snacks, and nutrition bars. While FDA has determined that it is unlawful to introduce into interstate commerce food to which CBD has been added, independent of CBD's status as a drug ingredient, CBD has not been approved as a food additive. FDA also has determined that "[b]ased on a lack of scientific information supporting the safety of CBD in food â¦ it cannot conclude that CBD is [GRAS] among qualified experts for its use in human or animal food." Animal Food and Feed Considerations As previously noted, the FFDCA definition of food includes animal food. Similar to food intended for human consumption, animal food is not subject to premarket approval by FDA unless it meets the definition of a food additive. In that case, it would be subject to the premarket requirements for food additives (or GRAS exemption). Depending on the claims made, certain animal feed/food may meet the FFDCA definition of a drug . Like human drugs, animal drugs require FDA approval prior to marketing. In some cases, animal food may be considered both a food and a drug simultaneously. Although premarket approval by FDA is not required for most animal food (excluding animal drugs), other federal and state rules govern their manufacture and sale. These include, for example, labeling requirements and ingredient definitions. As previously noted, it is a prohibited act, with certain exceptions, under the FFDCA to introduce into interstate commerce animal food to which a drug has been addedâeither an approved drug or a drug for which substantial clinical investigations have been instituted and made public. Some cannabis-derived ingredients that do not contain CBD or contain only trace amounts of CBD (e.g., hemp seed and ingredients derived from hemp seed) may fall outside the scope of this prohibition and may be lawfully marketed pursuant to FDA approval as a food additive or a GRAS determination. However, to date, FDA has not approved any food additive petitions or evaluated any GRAS notices related to use of hemp seed and hemp-seed derived ingredients in animal food. In addition, as previously mentioned, FDA has stated that "[b]ased on a lack of scientific information supporting the safety of CBD in food â¦ it cannot conclude that CBD is [GRAS] among qualified experts for its use in human or animal food." While FDA is the primary federal agency responsible for regulating the safety of food, the agency works with states and the Association of American Feed Control Officials (AAFCO) in the implementation of uniform policies for regulating the use of animal food products. For example, FDA provides scientific and technical assistance to the AAFCO ingredient Definition Request Process, the purpose of which is to "identify the safety, utility, and identity of ingredients used in animal feed." CVM recognizes ingredients listed in the Official Publication of the AAFCO as being acceptable for use in animal food. According to FDA, "there are no approved food additive petitions or ingredient definitions listed in the AAFCO OP for any substances derived from hemp, and we are unaware of any GRAS conclusions regarding the use of any substances derived from hemp in animal food." AAFCO has issued guidelines on hemp in animal food, which are generally consistent with FDA's policy. The guidelines also note that, based on discussions with FDA and the hemp industry, materials and products that are CBD-infused need to be treated as drugs because the intended uses are largely associated with drug claims. This means that parts of the hemp plant will not be appropriate for approval as an animal feed ingredient. As such, products that contain CBD as a feed ingredient could be labeled adulterated or misbranded and be subject to regulatory actions by state agencies. Dietary Supplements A dietary supplement is defined as a product (other than tobacco) that is intended to supplement the diet; is intended to be taken by mouth as a pill, capsule, powder, tablet, or liquid; and contains one or more of the following dietary ingredients: vitamins, minerals, herbs or other botanicals, amino acids, and other substances or their constituents. Dietary supplements are generally regulated as food under the FFDCA and, as such, are not subject to premarket approval. Dietary supplements must comply with FDA's regulations prescribing CGMPs related to manufacturing, packaging, labeling, or holding dietary supplements to ensure their quality. A dietary supplement may not claim to diagnose, cure, mitigate, treat, or prevent a specific disease or class of diseases. FDA does not evaluate the safety and effectiveness of dietary supplements prior to marketing; however, supplements are subject to various statutory and regulatory requirements. Among other things, a firm that seeks to market a dietary supplement containing a new dietary ingredient (NDI) must notify FDA at least 75 days prior to marketing. The manufacturer or distributor of the dietary supplement that contains an NDI subject to the notification requirements may not market the supplement until 75 days after the filing date. An NDI is defined as a dietary ingredient that was not marketed as a dietary supplement in the United States before October 15, 1994. An exception to the NDI notification requirement is if the dietary ingredient was "present in the food supply as an article used for food in a form in which the food has not been chemically altered." In this case, the dietary ingredient would still be considered an NDI because it was not marketed prior to October 15, 1994, but it would be exempt from the notification requirement. An NDI notification must include a "history of use or other evidence of safety establishing that the dietary ingredient, when used under the conditions recommended or suggested in the labeling of the dietary supplement, will reasonably be expected to be safe," along with other information. FDA acknowledges receipt of the NDI notification and notifies the submitter of the date of receipt, which is also the NDI notification filing date. FDA must keep the information in the NDI notification confidential for the first 90 days after receiving it. If the manufacturer or distributor submits additional information in support of the NDI notification, FDA may reset the 75-day period and assign a new filing date. FDA does not approve NDI notifications. Instead, the agency generally issues one of four response letters: (1) a letter of acknowledgment without objection; (2) a letter listing deficiencies that make the notification incomplete; (3) an objection letter raising safety concerns based on information in the notification or identifying gaps in the history of use or other evidence of safety; or (4) a letter raising other regulatory issues with the NDI or dietary supplement (e.g., the NDI or supplement is excluded from the definition of a dietary supplement). Under the FFDCA, an article that is an active ingredient in an approved drug, or that has been authorized for investigation as a new drug and for which the existence of such clinical investigations has been made public, is excluded from the definition of a dietary supplement and may not be marketed as such. An exception to this is if FDA issues a regulation finding that the use of such substance in a dietary supplement is lawful. An article that is approved as a drug or being investigated as a drug may be marketed in or as a dietary supplement if it was marketed as a dietary supplement or as a food prior to approval or clinical investigation (before the IND became effective). According to FDA, CBD is an active ingredient in an FDA-approved drug (i.e., Epidiolex), and it was authorized for investigation as a new drug for which substantial clinical investigations had been instituted and made public before its marketing as a dietary supplement. As such, FDA has determined that CBD may not be sold as a dietary supplement unless FDA promulgates regulations concluding otherwise, regardless of whether the CBD is hemp-derived or marijuana-derived. FDA has issued several public statements maintaining that it is unlawful to market CBD as, or in, dietary supplements. FDA may issue a regulation, after notice and comment, creating an exception that allows CBD to be marketed as a dietary supplement. Such a regulation may be requested by an interested person through the filing of a citizen petition. If an interested party has evidence challenging FDA's conclusion excluding CBD from the dietary supplement definition, the party may submit to FDA a citizen petition asking the agency to issue a regulation, subject to notice and comment, finding that the ingredient, when used as or in a dietary supplement, would be lawful. To date, FDA has not issued such a regulation for any substance (whether cannabis-derived or not) that is an active ingredient in an approved drug or is authorized for investigation as a new drug. If FDA were to issue a regulation allowing CBD to be marketed as a dietary supplement, that product likely would be expected to comply with the various requirements governing lawful marketing of supplements, including compliance with CGMPs and NDI notification. Despite FDA's determination that marketing CBD as a dietary supplement is unlawful, these products remain on the market. On November 14, 2019, the Consumer Healthcare Products Association (CHPA) submitted a citizen petition to FDA, asking the agency to "exercise its statutory authority and discretion to engage in rulemaking that establishes a regulatory pathway to legally market dietary supplements containing [CBD] derived from hemp (as defined in 7 U.S.C. Â§1639o(1))" and to require that manufacturers of CBD-containing dietary supplements submit NDI notifications. It is unclear whether other citizen petitions have been submitted to FDA requesting that it issue a regulation allowing CBD to be marketed as a dietary supplement. Cosmetics and Personal Care Products The FFDCA defines cosmetics as "(1) articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance and (2) articles intended for use as a component of any such articles; except that such term shall not include soap." FDA has the authority to take certain enforcement action against adulterated or misbranded cosmetics. A cosmetic is deemed adulterated if, among other things, it contains a poisonous or deleterious substance, or if it has been made or held in unsanitary conditions. A cosmetic is deemed misbranded if, among other things, "its labeling is false or misleading in any particular," or if the label lacks required information. In addition, if a product makes therapeutic claims (i.e., that its intended use is the cure, mitigation, treatment, or prevention of a disease), FDA generally considers that product to be a drug (or a drug-cosmetic) and subject to the FFDCA drug requirements. If a company has not obtained approval of a new drug prior to marketing, it is in violation of the FFDCA. For example, in October 2019, FDA sent a warning letter to a manufacturer marketing a CBD body butter with therapeutic claims. However, FDA's authority over cosmetic products is generally more limited than for the other products that the agency regulates. FDA does not have the authority to conduct premarket review of cosmetic ingredients, nor can FDA require cosmetics manufacturers to submit data substantiating the safety of their cosmetics. While FDA regulations prohibit or restrict the use of certain ingredients in cosmetics, the regulations do not apply to any cannabis or cannabis-derived ingredients (e.g., CBD). Legislation has been introduced in the 116 th Congress that would expand FDA's authority to regulate cosmetic products and would require a safety review of certain ingredients, among other things. If CBD were included in such a review and found to be unsafe for use in cosmetics, that finding would likely affect whether CBD could be marketed in cosmetics. Tobacco Products FDA regulates the manufacture, marketing, and distribution of tobacco products, per its authorities in the FFDCA, as amended by the Family Smoking Prevention and Tobacco Control Act of 2009 (TCA; P.L. 111-31 ). A tobacco product is defined as "any product made or derived from tobacco that is intended for human consumption, including any component, part, or accessory of a tobacco product (except for raw materials other than tobacco used in manufacturing a component, part, or accessory of a tobacco product)" that is not a drug, device, or drug-device combination product. Nicotine is an addictive chemical compound present in the tobacco plant. Tobacco productsâincluding cigarettes, cigars, smokeless tobacco, hookah tobacco, and most ENDSâcontain nicotine. Tobacco-derived nicotine (as well as any other tobacco-derived compound) meets the statutory definition of a tobacco product. In 2016, FDA promulgated regulations (known as the deeming rule ) that extend authority over all products meeting the definition of a tobacco product that were not already subject to the FFDCA, including ENDS. In the deeming rule, FDA clarified its authority to regulate all components and parts associated with ENDS, including e-liquids. E-liquids, which can include nicotine, flavorings, and other ingredients, are heated in ENDS to create a vapor that a user inhales. If an e-liquid contains CBD and makes therapeutic claims, it may be considered an unapproved drug and may be in violation of the FFDCA. In addition, if an e-liquid contains any tobacco-derived compound (e.g., nicotine) and CBD, but does not make therapeutic claims for CBD, the product may still meet the statutory definition of a tobacco product because it includes tobacco-derived compounds. In such case, the product may be subject to FDA's tobacco regulatory authorities, although the product might not receive marketing authorization if it is determined that allowing the product to be marketed would not be appropriate for the protection of public health. However, if the e-liquid contains CBD only, with no tobacco-derived compounds, and does not make therapeutic claims, FDA's enforcement options might be limited. In this case, it would be unclear whether the product meets the statutory definition of a tobacco product and is therefore subject to FDA's tobacco regulatory authorities. FDA has stated that it intends to make a determination about regulating such products as tobacco products on a case-by-case basis. Alcohol Beverage Products While TTB is the primary federal regulator of alcoholic beverages, FDA plays a role in determining what ingredients may be used in the production of alcoholic beverages. In general, before a hemp ingredient may be used in the production of an alcohol beverage productâwhether it be a distilled spirit, wine, or beerâthe producer may be required to request formula approval from TTB. Requirements are outlined in the Federal Alcohol Administration Act (27 U.S.C. Â§201 et seq.) and in regulation. For distilled spirits, for example, an approved formula is required to "blend, mix, purify, refine, compound, or treat spirits in a manner which results in a change of character, composition, class or type of the spirits;" any change in an approved formula requires a new filing. For wine, formula approval is required for "special natural wine, agricultural wine, and other than standard wine (except distilling material or vinegar stock)." For beer, formula approval is required for any fermented product that "is not generally recognized as a traditional process in the production of a fermented beverage designated as 'beer,' 'ale,' 'porter,' 'stout,' 'lager,' or 'malt liquor'" or to which certain ingredients are added. Specific labeling requirements also apply, and generally require prior approval. In addition, regarding interstate and foreign commerce in spirits, wine, and beer, it is unlawful for businesses to operate without a permit. Certain states and local jurisdictions might also have their own alcohol product prohibitions and production requirements, as well as restrictions on interstate commerce. TTB's current policy is that the agency "will not approve any formulas for alcohol beverages that contain ingredients that are controlled substances under the CSA" (e.g., marijuana or marijuana-derived CBD). With regard to CBD derived from hemp, TTB is in the process of updating its guidance on the use of hemp ingredients to reflect changes in the 2018 farm bill. TTB also states that it consults with FDA on ingredient safety issues and, in some cases, may "require formula applicants to obtain documentation from FDA indicating that the proposed use of an ingredient in an alcohol beverage would not violate [FFDCA]." Thus, in general, TTB treats hemp-derived ingredients for alcohol beverage products as any other product ingredient. As such, any ingredients added to alcohol beverage products must be either an FDA-approved food additive or determined to be GRAS. As aforementioned, to date, FDA has evaluated GRAS determinations for three different hemp seed-derived ingredients that do not contain CBD, although allowed uses do not include addition to alcoholic beverages. With regard to CBD, FDA has determined that it is unlawful to introduce into interstate commerce food to which certain drug ingredients (e.g., CBD) have been added. Additionally, independent of CBD's status as a drug ingredient, CBD has not been approved as a food additive, and FDA has determined that "[b]ased on a lack of scientific information supporting the safety of CBD in food â¦ it cannot conclude that CBD is [GRAS] among qualified experts for its use in human or animal food." Formulations seeking approval to use other types of hemp extracts as an ingredientâincluding but not limited to CBDâwould likely not be approved by TTB, since these extracts have not been authorized for use in food by FDA. Therapeutic Uses of CBD and ResearchÂ Considerations Cannabinoids such THC and CBD interact with specific cell receptors in the brain and throughout the body to produce their intended effects. Although THC activates certain receptors that then produce euphoric or intoxicating effects, CBD has low affinity for those same receptors and therefore does not produce intoxicating effects. This property may make CBD an attractive compound for drug developers. In addition, preclinical (e.g., animal model) research suggests that CBD may interact with other brain-signaling systems that can produce therapeutic effects, such as the reduction of seizures, pain, and anxiety. The therapeutic benefits, or underlying mechanism of action for therapeutic benefits, of CBD remain uncertain, even in CBD-containing drugs that have been approved by regulatory agencies. For example, in the United States, GW Pharmaceuticals' Epidiolex (CBD) is approved for the treatment of seizures associated with two rare and severe forms of epilepsy. However, according to the drug's labeling, the mechanism by which the drug exerts its anticonvulsant effects is not known. In addition, while not yet approved in the United States, GW Pharmaceuticals' drug Sativex (nabiximols)âa cannabis extract spray containing a 1:1 ratio of CBD and delta-9 THCâhas regulatory approval in more than 25 countries for the treatment of spasticity (muscle stiffness/spasm) due to multiple sclerosis (MS). In Canada, Sativex has conditional marketing authorization as an adjunctive treatment for neuropathic pain in adult patients with MS and "as adjunctive analgesic [pain relieving] treatment in adult patients with advanced cancer who experience moderate to severe pain during the highest tolerated dose of strong opioid therapy for persistent background pain." However, Phase III clinical trials previously conducted by GW Pharmaceuticals found that Sativex failed to show superiority over placebo in treating the pain of patients with advanced cancer who experience inadequate analgesia during optimized chronic opioid therapy. Furthermore, while CBD is predicted to have anti-inflammatory properties, which may play a role in its analgesic effects, preliminary evidence suggests that the analgesia is mediated by THC, and the extent to which CBD contributes to those therapeutic effects is unclear. CBD is the subject of numerous ongoing randomized controlled trials (RCTs). As of December 2019, a database maintained by the National Library of Medicine (NLM) at the National Institutes of Health (NIH) lists numerous domestic and international ongoing RCTs involving cannabinoidsâincluding CBDâas a treatment for a variety of conditions, including chronic pain, tremors associated with Parkinson's disease, and anxiety. GW Pharmaceuticals is also studying CBD and CBD variants in clinical trials for autism and schizophrenia. Other pharmaceutical manufacturers are conducting clinical trials with CBD and its variants for other indications, including severe acne and graft-versus-host disease (GVHD). However, until such studies are completed, conclusive evidence supporting the use of CBD to treat various health conditions is limited. In February 2017, the National Academies of Sciences, Engineering, and Medicine (NASEM) published a comprehensive review of fair- and good-quality systematic reviews of literature and high-quality primary research on cannabis and cannabinoids. NASEM did not make specific comparisons between cannabinoids derived from hemp versus marijuana, or between cannabinoids from low versus high THC strains of marijuana. However, for CBD or CBD-enriched cannabis specifically, the report noted research gaps among existing literature in treating numerous conditions, including cancer in general, chemotherapy-induced nausea, epilepsy, and post-traumatic stress disorder (PTSD), among other conditions. Nonetheless, CBD is promoted as treatment for a range of conditions, including PTSD, anxiety, inflammation, and sleeplessnessâdespite limited scientific evidence substantiating or disproving these claims. These research gaps can be attributed, in part, to the status of marijuana as a Schedule I controlled substance under the CSA. Individuals who seek to conduct research on any controlled substance must do so in accordance with the CSA and other federal laws. DEA research requirements are more stringent for Schedule I and Schedule II substances than for substances in Schedules III-V. For example, for Schedule I substances such as marijuana, even if practitioners have a DEA registration for a substance in Schedules II-V, they must obtain a separate DEA registration for researching a Schedule I substance. In addition, due to its Schedule I status, the DEA strictly limits the quantity of marijuana manufactured each year. These requirements can prolong the process of acquiring marijuana (including marijuana-derived CBD) for research. As mentioned previously, the 2018 farm bill removed hemp and hemp derivatives (including hemp-derived CBD) from the CSA definition of marijuana, making them no longer subject to regulation and oversight as a controlled substance by DEA. DEA has confirmed that a DEA registration is no longer required to grow or research hemp plants and CBD preparations that meet the statutory definition of hemp . However, CBD preparations containing above the 0.3% delta-9 THC level (i.e., meeting the statutory definition of marijuana) continue to be subject to Schedule I CSA requirements. As a result, conducting research on these substances may continue to be a challenge. Considerations for Congress: Marketing of CBD What Are the Circumstances Under Which FDA-Regulated Products Containing CBD Can Be MarketedÂ Currently? As mentioned previously, FDA has determined that at this time, CBD cannot be added to any food that is sold in interstate commerce and that CBD cannot be marketed as a dietary supplement. Although FDA could issue a regulation allowing CBD to be added to food or allowing its use in dietary supplements, the agency has never issued such a regulation for any substance (whether cannabis-derived or not) that is an approved drug or authorized for investigation as a new drug. Although FDA has determined that CBD (and THC) may not be added to food or marketed as a dietary supplement, the agency has not made this same determination for other compounds derived from cannabis, although those compounds may be subject to DEA restrictions; FDA's determination is specific to CBD and THC because both are active ingredients in FDA-approved drugs. FDA also has not determined that CBD may not be added to cosmetics; however, if a CBD-containing cosmetic product makes therapeutic claims (e.g., that it is intended to diagnose, treat, cure, mitigate, or prevent a disease), FDA would likely consider the product to be a drug subject to the new drug approval requirements. CBD may be lawfully marketed as a drug, pursuant to FDA approval, and in compliance with applicable statutory and regulatory requirements. If a firm seeks to market CBD as a treatment or an otherwise therapeutic product, the firm generally would need to obtain premarket approval from FDA via the new drug approval pathway. To date, FDA has approved one CBD-containing drug, Epidiolex, which is available by prescription for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients two years old and older. Epidiolex is marketed by GW Pharmaceuticals. On May 31, 2019, FDA held a public hearing "to obtain scientific data and information about the safety, manufacturing, product quality, marketing, labeling, and sale of products containing cannabis or cannabis-derived compounds." Prior to the hearing, FDA had opened a docket to which interested stakeholders could submit a request for FDA to review scientific data and information about products containing cannabis or cannabis-derived compounds. Although FDA has maintained that it is unlawful to add CBD to food or to market CBD as a dietary supplement, CBD continues to be marketed in violation of this determination. The agency has generally prioritized enforcement against companies and products that pose the greatest risk to consumersâfor example, products making claims that CBD can treat Alzheimer's or stop cancer cell growth. FDA has said that it "does not have a policy of enforcement discretion with respect to any CBD products," although this is expected to change in light of language included in the explanatory statement accompanying the FY2020 enacted appropriation (see " What Could Congress Do to Allow CBD to Be Marketed as a Food Additive or Dietary Supplement? "). Some industry stakeholders are recommending that, absent an FDA regulatory framework for CBD products, manufacturers and marketers of dietary supplements or foods that contain hemp or CBD comply with federal regulations for supplements and food in the interim to help ensure the quality of these CBD products. Such compliance would include facility registration, adherence to CGMPs, and meeting labeling requirements. In an effort to establish industry-wide standards, one organization has established its own third-party certification program designed for hemp food, dietary supplements, and cosmetic companies. This certification program is independent of federal requirements, and FDA has not validated or verified any third-party certification program for hemp. What Is the Current State of the CBD Market? At the retail level, consumer products labeled as containing CBD are being marketed and sold in food and beverages, cosmetics and personal care products, certain tobacco products, and dietary supplementsâdespite FDA's position that CBD may not be sold in food and beverages or dietary supplements. CBD-containing products that claim to meet the definition of hemp are sold through specialty retailers, such as natural/organic grocery stores, tobacco (or smoke) shops, yoga studios, and farmers' markets; through direct-to-consumer and online sales; from herbal practitioners; and by large retailers such as CVS and Walgreens. Although some industry analysts foresee a strong market for marijuana-derived CBD, it remains prohibited (aside for lawful research purposes) under the CSA if the product does not meet the statutory definition of hemp in 7 U.S.C. Â§1639o. The DEA has confirmed that a DEA registration is not required to grow or research hemp plants and CBD preparations that meet the statutory definition of hemp. Despite the federal prohibition on growing, selling, or possessing marijuana, marijuana-derived CBD products that have not been approved by FDA have been made available in states where medical and/or recreational cannabis is legal under state law, in violation of federal law. Depending on where a CBD product is manufactured and sold, it may primarily be produced using only drug-grade cannabis and marketed as a medicinal or therapeutic product, in violation of FDA requirements. To date, most of the CBD products sold in states where medical and/or recreational cannabis is legal do not meet the statutory definition of hemp. Typically, these products contain 0.45% to 1.5% THC, with some products containing up to 9% THCâlevels that could result in psychoactive effects by the user. In 2018, CBD sales in the United States were estimated at $534 million, according to the Hemp Business Journal . This amount includes sales from hemp-derived CBD products, marijuana-derived CBD products (currently a Schedule I controlled substance), and the FDA-approved drug Epidiolex. In 2018, more than 1,000 companies were producing and marketing CBD products for the U.S. market. Since 2014, when total CBD sales were a reported $108 million, U.S. sales of CBD have risen fivefold ( Figure 3 ). In 2018, hemp- and marijuana-derived CBD sales were $240 million and $264 million, respectively, while sales of Epidiolex were estimated at $30 million ( Figure 3 ). Current projections of U.S. sales of CBD indicate expected growth over the next few years. Such sales are expected to exceed $1 billion in 2020 and reach nearly $2 billion in 2022, roughly split between the three markets (hemp-derived, marijuana-derived, and pharmaceutical CBD; see Figure 3 ). Others forecast sales well beyond these levels, with some predicting that sales of hemp-derived CBD will eventually dominate the cannabis market, since hemp-derived CBD does not tend to carry the stigma associated with marijuana. An ATKearney survey shows that U.S. consumers, regardless of age, strongly believe that cannabis can "offer wellness and therapeutic benefits," ranging from 74% to 83% of those surveyed across all age demographics. Some global markets where cannabis is legal are already reporting product shortages of CBD medicinal cannabis products. In the United States, growth in CBD sales is expected despite continued regulatory and legal uncertainty, given continued FDA, DEA, and state and local restrictions. What Could Congress Do to Allow CBD to Be Marketed as a Food Additive or Dietary Supplement? Despite FDA's current determination that CBD cannot be marketed as a food additive or a dietary supplement, these products continue to be sold. In response, some members of Congress have expressed support for a regulatory framework for hemp-derived CBD in certain FDA-regulated consumer products. In absence of a regulatory framework for hemp-derived CBD products, Congress has directed FDA to issue a policy of enforcement discretion with respect to CBD products that meet the statutory definition of hemp that also come under FDA jurisdiction. More specifically, the explanatory statement accompanying the enacted FY2020 appropriation states that [t]he agreement includes $2,000,000 for research, policy evaluation, market surveillance, issuance of an enforcement discretion policy, and appropriate regulatory activities with respect to products under the jurisdiction of the FDA which contain CBD and meet the definition of hemp, as set forth in section 297A of the Agricultural Marketing Act of 1946 (7 U.S.C. 16390). Within 60 days of enactment of this Act, the FDA shall provide the Committees with a report regarding the agency's progress toward obtaining and analyzing data to help determine a policy of enforcement discretion and the process in which CBD meeting the definition of hemp will be evaluated for use in products. The FDA is further directed to perform a sampling study of the current CBD marketplace to determine the extent to which products are mislabeled or adulterated and report to the Committees within 180 days of enactment of this Act. The statement does not explicitly require FDA to set a safe level or threshold for CBD in consumer products. However, the activities conducted pursuant to this directive may inform the establishment of such a level in the future. In addition to the activities directed in the explanatory statement, Congress also could take further legislative action, such as requiring FDA to issue a regulation, under its FFDCA authorities, expressly permitting CBD that meets the definition of hemp to be used as a food additive or dietary supplement. For example, such a regulation could prescribe the conditions under which CBD may be safely used as a food additive (e.g., to add flavor or nutritional value to food, in specified quantities, subject to specified labeling requirements). However, because FDA has never before issued such a regulation allowing an approved drug or a substance authorized for investigation as a new drug to be a food additive or added to a dietary supplement, it is not clear what such a regulation would look like. Congress also could consider amending the FFDCA provisions that FDA has identified as restricting marketing of CBD in food and dietary supplements. For example, Congress could exclude from these provisions CBD that meets the statutory definition of hemp. However, even if the marketing of CBD-containing products were no longer restricted by these provisions, CBD-containing products may still be subject to other FFDCA requirements. For example, to lawfully market a CBD product as a dietary supplement, a firm may need to submit an NDI notification to FDA, in addition to meeting other statutory and regulatory requirements for supplements. To lawfully market CBD as a food additive, a firm would be expected to either obtain approval via a food additive petition or pursuant to a GRAS determination. As FDA has said that the agency "is not aware of any basis to conclude that CBD is GRAS among qualified experts for its use in human or animal food," a food additive petition may be necessary. As mentioned above, food and dietary supplements are not evaluated by FDA for safety and effectiveness prior to marketing. Given this fact, in determining whether a legislative approach is appropriate, Congress may consider the potential for adverse health effects and other unintended consequences. For example, clinical trials to support the approval of Epidiolex demonstrated the potential for liver injury at certain doses, and CBD may interact with other drugs or dietary supplements. Other concerns include the potential dosing and cumulative effects of exposure to CBD from multiple sources (e.g., food, supplements, and cosmetics); whether there are populations for whom CBD is not appropriate (e.g., pregnant or lactating women); and whether allowing CBD to be marketed as a supplement or food additive could undermine incentives for conducting clinical trials and obtaining evidence of safety and effectiveness to support drug approval. FDA's position with respect to the status of CBD impacts other agencies' and regulatory bodies' policies and guidance. For example, TTB consults with FDA on alcohol ingredient safety issues and generally requires that any ingredient added to alcohol beverages must be either an FDA-approved food additive or determined to be GRAS. CBD is not an approved food additive nor has it been found to be GRAS for use in alcohol or otherwise. It remains to be seen whether TTB would allow CBD that meets the definition of hemp to be added to alcoholic beverages if FDA issues a policy of enforcement discretion as directed by the explanatory statement accompanying the FY2020 enacted appropriation. Similarly, the AAFCO has issued guidelines on hemp in animal food, which are generally consistent with FDA's policy. A new policy of enforcement discretion issued pursuant to the language in the explanatory statement may affect AAFCO's guidelines. Additionally, in May 2019, the U.S. Patent and Trademark Office (USPTO) issued guidance that limits trademark registrations for CBD products. USPTO's guidance describes how it would review marks for cannabis and cannabis-related goods and services, and clarifies that compliance with federal law is a condition of federal trademark registration, regardless of the legality of the activities under state law. It further states that a "determination of whether commerce involving cannabis and cannabis-related goods and services is lawful requires consultation of several different federal laws," including the CSA, FFDCA, and the 2018 farm bill ( P.L. 115-334 ). Therefore, "registration of marks for foods, beverages, dietary supplements, or pet treats containing CBD will still be refused as unlawful under the FDCA, even if derived from hemp, as such goods may not be introduced lawfully into interstate commerce." Some claim that because the guidance does not specifically address cosmetic products, this could suggest that federal USPTO registration could be possible for such products; however, they also assert that USPTO is looking to FDA to further clarify conditions under which CBD foods, beverages, dietary supplements or pet treats may be lawfully marketed. Appendix A. Food Additive Petition Process and GRAS Notification Submission Food Additive Petition Process FDA has determined that CBD cannot be added to any food that is sold in interstate commerce. FDA is authorized to issue a regulation, after notice and comment, approving the use of a drug (e.g., CBD) as a food additive, although the agency has never done so for any substance. The FFDCA does not specify a process for FDA to issue such a regulation, other than that it must be after notice and comment. In regard to the process for food additive approval, FDA is authorized to "by order establish a regulation" that prescribes the conditions under which a food additive may be safely used. The issuance of such regulation may be proposed by FDA on its own initiative or by an interested person via submission of a food additive petition. A food additive petition must include, in addition to any explanatory or supporting data, the following information: the name and all pertinent information relating to the food additive, including its chemical identity and composition (if possible); a statement of the conditions of its proposed use, including directions, recommendations, and suggestions, and the proposed labeling; "all relevant data bearing on the physical or other technical effect such additive is intended to produce, and the quantity of such additive required to produce such effect"; a description of methods for determining the quantity of such additive in or on food, and any substance formed in or on food, because of its use; and full reports of safety investigations, including the methods and controls used in conducting such investigations. FDA may request that the petitioner also provide information about the manufacturing methods, facilities, and controls, as well as samples of the food additive (or articles used as its components) and samples "of the food in or on which the additive is proposed to be used." Additional requirements are specified in FDA regulations. Within 30 days of the petition filing date, FDA must publish notice in the Federal Register of the regulation proposed by the petitioner. Within 90 days of petition filing, FDA must issue either an order denying the petition or an order establishing a regulation prescribing the conditions under which the food additive may be used safely (e.g., particular foods in which it may be used, maximum quantity, labeling and directions). This 90-day period may be extended by FDA, as specified. FDA may not issue such a regulation if a fair evaluation of the data "fails to establish that the proposed use of the food additive, under the conditions of use to be specified in the regulation, will be safe," subject to specified limitations, or if a fair evaluation of the data "shows that the proposed use of the additive would promote deception of the consumer in violation of [the FFDCA] or would otherwise result in adulteration or in misbranding of food." FDA is authorized to fix a "tolerance limitation" if necessary to ensure safe use of the additive. In considering whether the use of a food additive is safe, FDA must consider, among other relevant factors, the probable consumption of the additive and cumulative effect in the diet. Any person adversely affected by such order may file objections with FDA and request a public hearing and may file for judicial review, as specified. Food additive regulations may be amended or repealed. An interested person may, for example, submit a food additive petition requesting issuance of a regulation allowing a new use of a previously approved additive. If a food additive is already subject to an FDA regulation for the proposed intended use, it does not require premarket approval via a petition. Instead, that food additive may be marketed by complying with the applicable food additive regulation. GRAS Notice Submission Any person may submit a notice to FDA expressing the view that a substance is GRAS and not subject to the premarket review requirements for food additives under FFDCA Section 409. A GRAS notice has seven parts, each of which must be included in a submission to FDA. If one of the seven parts of a GRAS notice is omitted, the submission must explain why that part does not apply. The seven parts of a GRAS notice are as follows: 1. signed statements and certification; 2. identity, method of manufacture, specifications, and physical or technical effect; 3. dietary exposure; 4. self-limiting levels of use; 5. experience based on common use in food before 1958; 6. narrative; and 7. a list of supporting data and information in the GRAS notice. FDA evaluates the submission to determine whether to file it and then informs the submitter of the agency's decision. If FDA decides to file the GRAS notice, the agency sends a letter to the submitter with the filing date. The regulations do not specify a filing deadline for FDA. The regulations do state that FDA is required to respond to a GRAS notice within 180 days of filing. FDA may extend that timeframe by 90 days as needed. Filed GRAS notices are made public by FDA. Appendix B. Abbreviations Used in this Report