Chronic pain is one of the most prevalent, costly, and disabling health conditions in the United States. Estimates show that more than 11 percent of the American population suffer from chronic pain, yet the federal pain research investment has been minimal. In parallel with a gradual increased recognition of the problems of treating chronic pain, the opioid epidemic has emerged as a growing public health emergency. The intersection of these two crises lies in the fact that an unintended consequence of treating pain has been an increasing number of opioid prescriptions and diversion of drugs for illicit purposes. In May 2017, the National Institutes of Health (NIH), and the National Institute on Drug Abuse announced a public?private partnership to develop solutions to the opioid crisis and cut in half the time it takes to develop non-addictive analgesics. To advance the planning of NIH's anticipated public?private partnerships, the National Academies' Forum on Neuroscience and Nervous Systems Disorders hosted a public workshop that brought together a diverse group of stakeholders from academia, federal agencies, advocacy organizations and companies developing therapeutics for pain and opioid use disorders. Participants discussed potential strategies to accelerate development of non-addictive pain medications and treatments for opioid use disorders. This publication summarizes the presentations and discussions from the workshop. Table of Contents Front Matter 1 Introduction and Background 2 Exploring Challenges to Developing Treatments for Pain and Opioid Use Disorders 3 Exploring the State of the Science and Preclinical Models for Pain Therapeutic Development 4 Clinical Development of Non-Addictive Pain Medications 5 Therapeutic Development for Opioid Use Disorders and Overdose Prevention and Reversal 6 PublicPrivate Partnerships to Advance Pain and Opioid Use Disorders Research and Development Appendix A References Appendix B Workshop Agenda Appendix C Registered Attendees

Psychiatric illnesses - such as major depressive disorder, anxiety disorder, substance use disorder, and posttraumatic stress disorder (PTSD) - are widely prevalent and represent a substantial health burden worldwide. Yet, conventional medications for mental illnesses often fail to provide relief to patients' disruptive and disabling symptoms. Existing and emerging evidence that psychedelics (e.g., LSD and psilocybin) and entactogens (e.g., MDMA) may be useful as tools to alleviate mental illness has sparked a renaissance of interest by investigators, clinicians, drug developers, and patient advocates in recent years. While promising data on therapeutic efficacy has energized research and development, resolving the mechanisms of action will be important for optimizing the efficacy and safety of these medicines. Further, evaluating the effect of psychedelics and entactogens on mood and behavior comes with unique challenges still in need of resolution. These include unresolved questions relating to blinding, placebo and nocebo effects, and the impact of psychosocial contexts. In response to this renewed interest, the National Academies of Sciences, Engineering, and Medicine's Forum on Neuroscience and Nervous System Disorders convened a workshop on March 29-30, 2022. The workshop brought together a diverse group of stakeholders to explore the use of psychedelics and entactogens as treatments for psychiatric disorders. This Proceedings of a Workshop summarizes the presentations and discussions of the workshop. Table of Contents Front Matter 1 Introduction and Background 2 History and Current Status of Psychedelics and Entactogens for the Treatment of Psychiatric Disorders 3 Mechanisms of Action and Key Research Gaps for Psychedelics and Entactogens 4 Advancing Clinical Development: Challenges and Opportunities 5 Anticipating Implementation to Guide Clinical Research and Development 6 Reflecting on the Road Ahead Appendix A: References Appendix B: Workshop Agenda

To examine the promise, concerns, and challenges related to neuroscience research using genetically modified nonhuman primates, the National Academies of Sciences, Engineering, and Medicine hosted a public workshop on October 4, 2018, bringing together an international group of experts and stakeholders representing academia, industry, laboratory animal management, disease-focused foundations, and federal agencies. The workshop was designed to explore the current state and future promise of research using genetically modified nonhuman primate models of disease to understand the complex functions of the brain that control behavior, movement, and cognition in both health and disease states. This publication summarizes the presentations and discussions from the workshop. Table of Contents Front Matter 1 Introduction and Background 2 Genetically Modified Nonhuman Primate Models for Neuroscience Research: Rationale and Overview of Potential Opportunities and Challenges 3 State of the Science of Transgenic Nonhuman Primate Models for Nervous System Disorders 4 Translating Research from Nonhuman Primates to Humans 5 Bioethical Considerations for Transgenic Nonhuman Primate Models in Neuroscience Research 6 Understanding the Policy, Infrastructure, and Funding Needed to Advance Neuroscience Research Appendix A: References Appendix B: Workshop Agenda Appendix C: Registered Attendees

Neuroinflammation is a burgeoning area of interest in academia and biopharma, with a broadly acknowledged role in many central nervous system (CNS) disorders. However, there is little agreement on the pathophysiological mechanisms that underlie the manifestations of neuroinflammation in the CNS compartment and how neuroinflammation operates as a driver and also as a consequence of disease in the brain. Moreover, another unclear area is how to translate increased understanding of the mechanisms that underlie neuroinflammation and its manifestations in the CNS to therapeutics. To address these gaps in understanding mechanisms and how to translate that understanding into therapeutics, the Forum on Neuroscience and Nervous System Disorders of the National Academies of Sciences, Engineering, and Medicine convened a workshop on March 20-21, 2017, bringing together key leaders in the field from industry, academia, and governmental agencies to explore the role and mechanisms of neuroinflammation in a variety of CNS diseases. The workshop also considered strategies to advance the identification and validation of biomarkers of neuroinflammation that could accelerate development of therapies, bringing much-needed treatments to patients with disorders ranging from neuroinflammatory diseases such as multiple sclerosis (MS) to neuropsychiatric disorders such as depression. This publication summarizes the presentations and discussions from the workshop. Table of Contents Front Matter 1 Introduction and Overview 2 Biomarkers of Neuroinflammation: Challenges and Potential Opportunities 3 State of the Science of Neuroinflammation in Central Nervous System Disorders 4 Neuroinflammation in Disease 5 Neuroimaging Biomarkers: Current Initiatives and Opportunities 6 Cerebrospinal Fluid and Other Fluid Biomarkers: Current Initiatives and Opportunities 7 Potential Mechanisms for Moving Forward Appendix A References Appendix B Workshop Agenda Appendix C Registered Attendees

Compared with other disease areas, central nervous system (CNS) disorders have had the highest failure rate for new compounds in advanced clinical trials. Most CNS drugs fail because of efficacy, and the core issue underlying these problems is a poor understanding of disease biology. Concern about the poor productivity in neuroscience drug development has gained intensity over the past decade, amplified by a retraction in investment from the pharmaceutical industry. This retreat by industry has been fueled by the high failure rate of compounds in advanced clinical trials for nervous system disorders. In response to the de-emphasis of CNS disorders in therapeutic development relative to other disease areas such as cancer, metabolism, and autoimmunity, the National Academies of Sciences, Engineering, and Medicine initiated a series of workshops in 2012 to address the challenges that have slowed drug development for nervous system disorders. Motivated by the notion that advances in genetics and other new technologies are beginning to bring forth new molecular targets and identify new biomarkers, the Academies hosted the third workshop in this series in September 2016. Participants discussed opportunities to accelerate early stages of drug development for nervous system disorders in the absence of animal models that reflect disease and predict efficacy. This publication summarizes the presentations and discussions from the workshop. Table of Contents Front Matter 1 Introduction and Overview 2 Drug Development for Nervous System Disorders: Overview of Challenges and Potential Opportunities 3 Case Studies: Therapeutic Development for Parkinson's Disease and Schizophrenia in the Absence of Predictive Animal Models of Disease 4 New Modeling Approaches for Nervous System Disorders 5 Private-Sector Thresholds for Investment in Neuroscience Clinical Trials 6 Ethical Considerations 7 Regulatory Perspectives Appendix A: References Appendix B: Workshop Agenda Appendix C: Registered Attendees

In 2011 the Grand Challenges in Global Mental Health initiative identified priorities that have the potential to make a significant impact on the lives of people with mental, neurological, and substance use disorders. Reduction of the cost and improvement of the supply of effective medicines was highlighted as one of the top five challenges. For low- and middle-income countries, improving access to appropriate essential medicines can be a tremendous challenge and a critical barrier to scaling up quality care for mental, neurological, and substance use disorders. Reduction of cost and improvement of the supply of effective medicines has the potential to significantly impact the lives of patients with these disorders. Improving Access to Essential Medicines for Mental, Neurological, and Substance Use Disorders in Sub-Saharan Africa is the summary of a workshop convened by the Institute of Medicine Neuroscience Forum in January 2014 in Addis Ababa, Ethiopia to discuss opportunities for achieving long-term affordable access to medicines for these disorders. This report examines challenges and opportunities for improving access to essential medicines in four critical areas: demand, selection, supply chains, and financing and pricing. The report also discusses successful activities that increase access to essential medicines both within Sub-Saharan Africa and in other developing countries, and considers the role of governments, nongovernmental organizations, and private groups in procurement of essential medicines for mental, neurological, and substance use disorders. Table of Contents Front Matter 1 Introduction and Overview 2 Challenge: Insufficient Demand 3 Challenge: Inappropriate Selection 4 Challenge: Ineffective Supply Chains 5 Challenge: High Pricing and Poor Financing 6 Perspectives on Next Steps Appendix A: Access to Essential Medicines: Program Examples Appendix B: References Appendix C: Workshop Agenda Appendix D: Registered Attendees

Methadone is a Food and Drug Administration- (FDA-) approved medication for treating opioid use disorder (OUD), a chronic brain disease that affects more than 2.7 million people in the United States aged 12 and older. Despite its effectiveness in saving lives, many barriers impede access to, initiation of, and retention in methadone treatment for OUD. To address these barriers, on March 3 and 4, 2022, the National Academies of Sciences, Engineering, and Medicine hosted a workshop on "Methadone Treatment for Opioid Use Disorder: Examining Federal Regulations and Laws," at the request of the Office of National Drug Control Policy in the Executive Office of the President. This publication summarizes the presentation and discussion of the workshop. Table of Contents Front Matter 1 Introduction and Background 2 Methadone Treatment: Personal Perspectives 3 The History of Methadone and Barriers to Access for Different Populations 4 Current Federal Priorities and Regulatory Flexibilities during the COVID-19 Pandemic 5 Improving Access to Quality Treatment in Opioid Treatment Programs through Regulatory Innovation 6 Improving Access to Quality Treatment in the Criminal Justice System and Other Institutional Settings 7 Expanding Access to Methadone through Regulatory Innovation: Envisioning Approaches Outside the Opioid Treatment Program System 8 Ensuring Equitable Access to Methadone by Removing Current Barriers and Providing Incentives 9 Frameworks to Guide the Assessment of Legal and Regulatory Challenges 10 Moving Forward: Potential Concrete Legal and Regulatory Actions Appendix A: References Appendix B: Workshop Agenda Appendix C: Commissioned Papers

While significant progress has been seen in fields such as cardiovascular medicine and cancer in improving patient stratification and developing targeted drugs based on genetic findings, progress continues to lag for neuropsychiatric disorders. To address this issue, the National Academies of Sciences, Engineering, and Medicine's Forum on Neuroscience and Nervous System Disorders convened a workshop in October 2021. The workshop brought together government, philanthropic foundations, and disease-focused non--profit organizations to discuss new genetic and neuroscience technologies and explore how they can be used to elucidate disease mechanisms and to advance the development of biomarkers and targeted therapies for people with neurological and psychiatric disorders. This Proceedings of a Workshop summarizes the presentations and discussions of the workshop. Table of Contents Front Matter 1 Introduction and Background 2 Leveraging New Genetic and Neuroscience Technologies to Advance Therapeutic Development: Opportunities and Challenges 3 Increasing Ancestral Diversity to Enable Precision Medicine for Neurological and Psychiatric Disorders 4 Leveraging New Methodologies to Interpret Genetic Data in Neurological and Psychiatric Disorders 5 Identifying and Validating Molecular Pathways Using New Technologies for Human Biology 6 Enabling Patient Stratification through Deep Phenotyping and Biomarker Discovery 7 Potential Next Steps: Shifting the Trajectory of Treatment Development for Neurological and Psychiatric Disorders Appendix A: References Appendix B: Workshop Agenda

Accumulating evidence gathered over the past three decades has demonstrated a biological basis for differences between men and women with respect to clinical features and treatment responses to several neuropsychiatric, neurodevelopmental, and neurodegenerative disorders. Dramatic sex differences have also been identified in the brain transcriptomes of individuals with multiple brain disorders, including depression, posttraumatic stress disorder, and autism. The brain transcriptome includes all of the messenger RNA as well as the non-protein-coding RNA molecules expressed in brain tissue and thus represents gene activity. To explore these sex-based transcriptomic differences further, the National Academies of Sciences, Engineering, and Medicine's Forum on Neuroscience and Nervous System Disorders hosted a workshop on September 23, 2020, titled Sex Differences in Brain Disorders: Emerging Transcriptomic Evidence and Implications for Therapeutic Development. The workshop brought together a broad spectrum of stakeholders to share cutting-edge emerging evidence, discuss challenges, and identify future opportunities and potential directions. This publication summarizes the presentation and discussion of the workshop. Table of Contents Front Matter 1 Introduction and Background 2 Transcriptomic Evidence for Sex Differences in Stress- and Reward-Related Disorders 3 Transcriptomic Evidence for Sex Differences in Neurodevelopmental and Neurodegenerative Disorders 4 Moving Forward Appendix A: References Appendix B: Workshop Agenda

Pain is a leading cause of disability globally. The dramatic increase in opioid prescriptions within the past decade in the United States has contributed to the opioid epidemic the country currently faces, magnifying the need for longer term solutions to treat pain. The substantial burden of pain and the ongoing opioid crisis have attracted increased attention in medical and public policy communities, resulting in a revolution in thinking about how pain is managed. This new thinking acknowledges the complexity and biopsychosocial nature of the pain experience and the need for multifaceted pain management approaches with both pharmacological and nonpharmacological therapies. The magnitude and urgency of the twin problems of chronic pain and opioid addiction, combined with the changing landscape of pain management, prompted the National Academies of Sciences, Engineering, and Medicine to convene a workshop on December 4?5, 2018, in Washington, DC. The workshop brought together a diverse group of stakeholders to discuss the current status of nonpharmacological approaches to pain management, gaps, and future directions. This publication summarizes the presentations and discussions from the workshop. Table of Contents Front Matter 1 Introduction and Background 2 Workshop Context: Lived Experience, Provider Perspectives, and Current Patterns of Usage 3 Effectiveness, Safety, and Cost-Effectiveness of Nonpharmacological and Nonsurgical Therapies for Chronic Pain 4 Emerging Models of Care 5 Major Current Research Initiatives and Priorities 6 Education and Training of Health Professionals in Pain Management 7 Policies to Address Barriers to the Use of Evidence-Based Nonpharmacological Approaches to Pain Management 8 Future Directions Appendix A: References Appendix B: Workshop Agenda Appendix C: Registered Attendees

Technological advances in noninvasive neuroimaging, neurophysiology, genome sequencing, and other methods together with rapid progress in computational and statistical methods and data storage have facilitated large-scale collection of human genomic, cognitive, behavioral, and brain-based data. The rapid development of neurotechnologies and associated databases has been mirrored by an increase in attempts to introduce neuroscience and behavioral genetic evidence into legal proceedings. In March 2018, the National Academies of Science, Engineering and Medicine organized a workshop in order to explore the current uses of neuroscience and bring stakeholders from neuroscience and legal societies together in both the United Kingdom and the United States. Participants worked together to advance an understanding of neurotechnologies that could impact the legal system and the state of readiness to consider these technologies and where appropriate, to integrate them into the legal system. This publication summarizes the presentations and discussions from the workshop. Table of Contents Front Matter 1 Introduction and Background 2 Use of Neurotechnologies and Neuroscience in Legal Settings: Case Studies 3 Looking into the Future: Novel Uses of Emerging Neurotechnologies with Potential Legal Applications 4 Developing a Framework for Use of Evidence from Emerging Neurotechnologies 5 Moving Forward: Potential Next Steps Appendix A References Appendix B Workshop Agenda Appendix C Registered Attendees

On March 3-4, 2016, the National Academies of Sciences, Engineering, and Medicine's Forum on Neuroscience and Nervous System Disorders held a workshop in Washington, DC, bringing together key stakeholders to discuss opportunities for improving the integrity, efficiency, and validity of clinical trials for nervous system disorders. Participants in the workshop represented a range of diverse perspectives, including individuals not normally associated with traditional clinical trials. The purpose of this workshop was to generate discussion about not only what is feasible now, but what may be possible with the implementation of cutting-edge technologies in the future. Table of Contents Front Matter 1 Introduction 2 Neuroscience Clinical Trials: An Overview of Challenges and Potential Opportunities 3 Clinical Trial Design 4 Transforming Clinical Trials with Technology 5 The Regulatory Landscape: International Opportunities and Challenges 6 Ethical Considerations 7 Improving the Evidence Base for Real-World Use Appendix A: References Appendix B: Workshop Agenda Appendix C: Registered Attendees

From its very beginning, neuroscience has been fundamentally interdisciplinary. As a result of rapid technological advances and the advent of large collaborative projects, however, neuroscience is expanding well beyond traditional subdisciplines and intellectual boundaries to rely on expertise from many other fields, such as engineering, computer science, and applied mathematics. This raises important questions about to how to develop and train the next generation of neuroscientists to ensure innovation in research and technology in the neurosciences. In addition, the advent of new types of data and the growing importance of large datasets raise additional questions about how to train students in approaches to data analysis and sharing. These concerns dovetail with the need to teach improved scientific practices ranging from experimental design (e.g., powering of studies and appropriate blinding) to improved sophistication in statistics. Of equal importance is the increasing need not only for basic researchers and teams that will develop the next generation of tools, but also for investigators who are able to bridge the translational gap between basic and clinical neuroscience. Developing a 21st Century Neuroscience Workforce is the summary of a workshop convened by the Institute of Medicine's Forum on Neuroscience and Nervous System Disorders on October 28 and 29,2014, in Washington, DC, to explore future workforce needs and how these needs should inform training programs. Workshop participants considered what new subdisciplines and collaborations might be needed, including an examination of opportunities for cross-training of neuroscience research programs with other areas. In addition, current and new components of training programs were discussed to identify methods for enhancing data handling and analysis capabilities, increasing scientific accuracy, and improving research practices. This report highlights the presentation and discussion of the workshop. Table of Contents Front Matter 1 Introduction and Overview 2 Training Neuroscientists in Basic Research, Tool and Technology Development, and Big Data 3 Improving Training in Protocol Design, Experimental Rigor, and Quantitative Skills 4 Training in Transdisciplinary Research 5 Enhancing Training to Support Translational Research Appendix A: References Appendix B: Workshop Agenda Appendix C: Registered Attendees Appendix D: Participant Biographies

Humans are potentially exposed to more than 80,000 toxic chemicals in the environment, yet their impacts on brain health and disease are not well understood. The sheer number of these chemicals has overwhelmed the ability to determine their individual toxicity, much less potential interactive effects. Early life exposures to chemicals can have permanent consequences for neurodevelopment and for neurodegeneration in later life. Toxic effects resulting from chemical exposure can interact with other risk factors such as prenatal stress, and persistence of some chemicals in the brain over time may result in cumulative toxicity. Because neurodevelopmental and neurodegenerative disorders - such as attention-deficit hyperactivity disorder and Parkinson's disease - cannot be fully explained by genetic risk factors alone, understanding the role of individual environmental chemical exposures is critical. On June 25, 2020, the National Academies of Sciences, Engineering, and Medicine's Forum on Neuroscience and Nervous System Disorders hosted a workshop to lay the foundation for future advances in environmental neuroscience. The workshop was designed to explore new opportunities to bridge the gap between what is known about the genetic contribution to brain disorders and what is known, and not known, about the contribution of environmental influences, as well as to discuss what is known about how genetic and environmental factors interact. This publication summarizes the presentation and discussion of the workshop. Table of Contents Front Matter 1 Introduction and Background 2 Neurotoxicants and Their Risks to Human Health 3 The Exposome and Exploring the Multiple Factors That Contribute to Neurotoxicity 4 Chemical Toxicants as Drivers of Abnormal Neurodevelopment and Neurodegeneration 5 Research Gaps and Opportunities 6 Potential Opportunities for Action and Multidisciplinary Collaborations Appendix A: References Appendix B: Workshop Agenda

Improving and Accelerating Therapeutic Development for Nervous System Disorders is the summary of a workshop convened by the IOM Forum on Neuroscience and Nervous System Disorders to examine opportunities to accelerate early phases of drug development for nervous system drug discovery. Workshop participants discussed challenges in neuroscience research for enabling faster entry of potential treatments into first-in-human trials, explored how new and emerging tools and technologies may improve the efficiency of research, and considered mechanisms to facilitate a more effective and efficient development pipeline. There are several challenges to the current drug development pipeline for nervous system disorders. The fundamental etiology and pathophysiology of many nervous system disorders are unknown and the brain is inaccessible to study, making it difficult to develop accurate models. Patient heterogeneity is high, disease pathology can occur years to decades before becoming clinically apparent, and diagnostic and treatment biomarkers are lacking. In addition, the lack of validated targets, limitations related to the predictive validity of animal models - the extent to which the model predicts clinical efficacy - and regulatory barriers can also impede translation and drug development for nervous system disorders. Improving and Accelerating Therapeutic Development for Nervous System Disorders identifies avenues for moving directly from cellular models to human trials, minimizing the need for animal models to test efficacy, and discusses the potential benefits and risks of such an approach. This report is a timely discussion of opportunities to improve early drug development with a focus toward preclinical trials.

The BioWatch program, funded and overseen by the Department of Homeland Security (DHS), has three main elements-sampling, analysis, and response-each coordinated by different agencies. The Environmental Protection Agency maintains the sampling component, the sensors that collect airborne particles. The Centers for Disease Control and Prevention coordinates analysis and laboratory testing of the samples, though testing is actually carried out in state and local public health laboratories. Local jurisdictions are responsible for the public health response to positive findings. The Federal Bureau of Investigation is designated as the lead agency for the law enforcement response if a bioterrorism event is detected. In 2003 DHS deployed the first generation of BioWatch air samplers. The current version of this technology, referred to as Generation 2.0, requires daily manual collection and testing of air filters from each monitor. DHS has also considered newer automated technologies (Generation 2.5 and Generation 3.0) which have the potential to produce results more quickly, at a lower cost, and for a greater number of threat agents. Technologies to Enable Autonomous Detection for BioWatch is the summary of a workshop hosted jointly by the Institute of Medicine and the National Research Council in June 2013 to explore alternative cost-effective systems that would meet the requirements for a BioWatch Generation 3.0 autonomous detection system, or autonomous detector, for aerosolized agents . The workshop discussions and presentations focused on examination of the use of four classes of technologies-nucleic acid signatures, protein signatures, genomic sequencing, and mass spectrometry-that could reach Technology Readiness Level (TRL) 6-plus in which the technology has been validated and is ready to be tested in a relevant environment over three different tiers of temporal timeframes: those technologies that could be TRL 6-plus ready as part of an integrated system by 2016, those that are likely to be ready in the period 2016 to 2020, and those are not likely to be ready until after 2020. Technologies to Enable Autonomous Detection for BioWatch discusses the history of the BioWatch program, the role of public health officials and laboratorians in the interpretation of BioWatch data and the information that is needed from a system for effective decision making, and the current state of the art of four families of technology for the BioWatch program. This report explores how the technologies discussed might be strategically combined or deployed to optimize their contributions to an effective environmental detection capability. Table of Contents Front Matter 1 Introduction 2 Overview of the BioWatch Program 3 Public Health's Perspective on the Role of BioWatch in the Decision-Making Process 4 Potential Technologies for the BioWatch Program 5 Final Thoughts Appendix A: References Appendix B: Biographical Sketches of Workshop Participants Appendix C: Workshop Agenda Appendix D: Registered Attendees Appendix E: Technology Readiness Levels in the Department of Defense Appendix F: White Paper 1: The BioWatch Program: What Information Is Needed to Inform Decision Making? Appendix G: White Paper 2: Nucleic-Acid Signatures at Three Levels of Readiness for BioWatch Appendix H: White Paper 3: State of the Art for Autonomous Detection Systems Using Immunoassays and Protein Signatures Appendix I: White Paper 4: State of the Art for Autonomous Detection Systems Using Genomic Sequencing Appendix J: White Paper 5: State of the Art for Autonomous Detection Systems Using Mass Spectrometry

The Institute of Medicine (IOM) Forum on Neuroscience and Nervous System Disorders, in collaboration with the IOM Forum on Drug Discovery, Development, and Translation, convened a workshop on January 20-21, 2015, to explore policy changes that might increase private sector investment in research and development innovation that fills unmet medical needs for central nervous system (CNS) disorders. Workshop participants strategized about how to incentivize companies to fortify their CNS drug development programs, shrinking obstacles that currently deter ventures. Representatives from academia, government agencies, patient groups, and industry gathered to share information and viewpoints, and to brainstorm about budget-neutral policy changes that could help widen the pipeline toward drugs that address unmet needs for CNS disorders. This report summarizes the presentations and discussion of the workshop. Table of Contents Front Matter 1 Introduction and Overview 2 Improving Market Protection 3 Strengthening the Regulatory Pathway 4 Patient Benefit and Engagement Appendix A: References Appendix B: Workshop Agenda Appendix C: Registered Attendees Appendix D: Participant Biographies