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

On April 23 and 24, 2019 the Forum on Neuroscience and Nervous System Disorders convened a workshop titled "Advancing Gene-Targeted Therapies for Central Nervous System Disorders" in Washington, DC. This public workshop brought together experts and key stakeholders from academia, government, industry, philanthropic foundations, and disease/patient-focused nonprofit organizations to explore approaches for advancing the development of gene-targeted therapies for central nervous system (CNS) disorders, and implications of developing these therapies. Participants explored lessons learned from both successful and unsuccessful clinical development programs; new knowledge about the genetic underpinnings of brain disorders; the current status and future potential of gene-targeted therapies for CNS disorders; challenges and potential solutions for translating preclinical findings to approved therapies; and patient and caregiver perspectives. They also discussed what will be needed to develop these therapies for common disorders such as Alzheimer's and Parkinson's disease, as well as neuropsychiatric and neurodevelopmental disorders such as schizophrenia and autism. The workshop included approaches that target both DNA and RNA, as well as gene products using viral vectors, antisense oligonucleotides, and RNA interference. This publication summarizes the presentations and discussion of the workshop. Table of Contents Front Matter 1 Introduction and Overview 2 Exploring the Current Landscape of Central Nervous System Gene-Targeted Therapies 3 Gene-Targeted Therapy Approaches for Central Nervous System Disorders: Opportunities and Challenges 4 Translating Gene-Targeted Therapies from Bench to Bedside 5 Meaningful Engagement of Patients and Families 6 Future Directions in the Development of Gene-Targeted Therapies Appendix A: References Appendix B: Workshop Agenda Appendix C: Registered Attendees

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

The cloud model of data sharing has led to a vast increase in the quantity and complexity of data and expanded access to these data, which has attracted many more researchers, enabled multi-national neuroscience collaborations, and facilitated the development of many new tools. Yet, the cloud model has also produced new challenges related to data storage, organization, and protection. Merely switching the technical infrastructure from local repositories to cloud repositories is not enough to optimize data use. To explore the burgeoning use of cloud computing in neuroscience, the National Academies Forum on Neuroscience and Nervous System Disorders hosted a workshop on September 24, 2019. A broad range of stakeholders involved in cloud-based neuroscience initiatives and research explored the use of cloud technology to advance neuroscience research and shared approaches to address current barriers. This publication summarizes the presentation and discussion of the workshop. Table of Contents Front Matter 1 Introduction and Background 2 Harnessing Cloud-Based Technologies to Advance Neuroscience Research: Select Current Initiatives Part 1: Cloud-Based Technologies for Neuroscience Research: Challenges and Potential Solutions 3 Protecting Privacy in the Cloud 4 Managing Data and Promoting Interoperability in the Cloud 5 Assigning Credit, Determining Ownership, and Licensing Data in the Cloud 6 Governing, Funding, and Sustaining Cloud-Based Platforms Part 2: Different Types of Neuroscience Data: Challenges and Potential Opportunities 7 Clinical Trial and Research Data 8 Genetic Data 9 Neuroimaging Data 10 Real-World Data 11 Future Directions Appendix A: References Appendix B: Workshop Agenda Appendix C: Registered In-Person 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

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

Multimodal therapy approaches that combine interventions aimed at different aspects of disease are emerging as potential?and perhaps essential?ways to enhance clinical outcomes for patients with psychiatric and neurological disorders. In order to examine the general principles underlying multimodal therapies and to explore challenges, potential barriers, and opportunities for their development, the National Academies of Sciences, Engineering, and Medicine convened a workshop in June 2016. Participants explored scientific, clinical, regulatory, and reimbursement issues related to multimodal approaches and potential opportunities to enhance clinical outcomes for individuals with nervous system disorders. This publication summarizes the presentations and discussions from the workshop. Table of Contents Front Matter 1 Introduction 2 Multimodal Therapy: Overview of Principles, Barriers, and Opportunities 3 Exploring the State of the Science 4 Regulatory and Reimbursement Considerations 5 Trial Designs to Establish Efficacy and Safety in Multimodal Therapies 6 Developing Multimodal Therapies: Practical Considerations Relating to Industry 7 Role of Research Funders in Multimodal Therapy Development Appendix A: References Appendix B: Workshop Agenda Appendix C: Registered Participants

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

Health information technology is providing patients, clinicians, and researchers with access to data that will enable novel approaches to science and medicine. Digital health records (DHRs) are capable of being shared across different health care settings for the examination of possible trends and long-term changes in a patient's disease progression or status as well as the effectiveness of the health care delivery system. While prevalence of paper records remains high, there has been a rapid trend toward the digitalization of medical and health records in many countries. DHRs are widely viewed as essential for improving health, reducing medical errors, and lowering costs. However, given that these databases have the potential to house the complete medical and health information of individuals, the potential misuse, de-identification or breaching of this data may have serious implications. On July 20, 2015, the Institute of Medicine's Forum on Neuroscience and Nervous System Disorders held a public session at the 2015 Alzheimer's Association International Conference to assess the impact of DHRs on Alzheimer's disease (AD) research. An estimated 46.8 million people worldwide are currently living with dementia, and the prevalence is expected to double every year for the next 20 years. Given the few therapies currently available to treat the symptoms of AD, compared to other central nervous system disorders, participants explored how DHRs may be used to help improve clinical trial design and methodology for AD research. This report summarizes the presentations and discussions from this workshop. Table of Contents Front Matter 1 Introduction and Overview 2 Building Infrastructure to Enable Data Sharing and Management 3 Ethical, Legal, and Societal Considerations 4 Potential Next Steps Appendix A: References Appendix B: Workshop Agenda Appendix C: Participant Biographies

Major depressive disorder (MDD) is recognized worldwide as a major cause of disability, morbidity, and mortality. According to the World Health Organization, unipolar depressive disorders affect more than 150 million people around the world and represent the leading cause of years lost due to disability among both men and women. In the United States alone, nearly 8 percent of persons over the age of 12 report current depression. MDD has long been defined primarily as a mood disorder. However,more recently people have begun to recognize effects on cognition as a major contributor to the disablement that accompanies depression and to consider this an underrecognized treatment target for depression. To explore how best to enable the discovery, development, and translation of treatments for cognitive dysfunction in depression, including a focus on the regulatory path forward, the Institute of Medicine's Forum on Neuroscience and Nervous Disorders convened key stakeholders at a workshop in February 2015. This report summarizes the presentations from expert speakers and discussions among workshop participants. Table of Contents Front Matter 1 Introduction and Overview 2 The Burden of Cognitive Dysfunction in Depression 3 State of the Science: Treatment Development 4 Challenges and Potential Solutions to Enable Development of Successful Treatments 5 Regulatory Issues 6 Lessons Learned from the Schizophrenia Field Appendix A: References Appendix B: Workshop Agenda Appendix C: Registered Attendees

Based on advances in biotechnology and neuroscience, non-invasive neuromodulation devices are poised to gain clinical importance in the coming years and to be of increasing interest to patients, clinicians,health systems, payers, and industry. Evidence suggests that both therapeutic and non-therapeutic applications of non-invasive neuromodulation will continue to expand in coming years, particularly for indications where treatments are currently insufficient, such as drug-resistant depression. Given the growing interest in non-invasive neuromodulation technologies, the Institute of Medicine's Forum on Neuroscience and Nervous System Disorders convened a workshop, inviting a range of stakeholders - including developers of devices and new technologies, researchers, clinicians, ethicists, regulators, and payers - to explore the opportunities, challenges, and ethical questions surrounding the development, regulation, and reimbursement of these devices for the treatment of nervous system disorders as well as for non-therapeutic uses, including cognitive and functional enhancement. This report highlights the presentation and discussion of the workshop. Table of Contents Front Matter 1 Introduction 2 Overview of Gaps, Challenges, and Potential Opportunities 3 The Science and Technology of Non-Invasive Neuromodulation 4 Therapeutic Uses of Non-Invasive Neuromodulation 5 Using Non-Invasive Neuromodulation for Diagnosis and Research 6 Enhancement of Brain Function and Performance 7 Ethical, Legal, and Social Issues 8 Regulatory Issues 9 Reimbursement Issues 10 The Business Environment Appendix A: References Appendix B: Workshop Agenda Appendix C: Registered Attendees

The critical importance of using mobile technology is clear to anyone in the health professions, particularly those who treat people with central nervous system (CNS) disorders. To explore current developments and opportunities for using mobile technology to advance research and treatment of CNS disorders, the National Academies' Forum on Neuroscience and Nervous System Disorders hosted a workshop in June 5?6, 2018. This publication summarizes the presentations and discussions at the workshop. Table of Contents Front Matter 1 Introduction and Background 2 Exploring Opportunities Afforded by Mobile Technology 3 Transforming Digital Data into Insight: Collection, Analysis, Standardization, and Validation 4 Regulatory Considerations and Pathways 5 Integrating Mobile Technology into Clinical Practice 6 Designing Mobile Technologies for Research and Clinical Practice That Reflect Patient Attitudes and Preferences 7 Moving Forward by Building Partnerships Appendix A: References Appendix B: Workshop Agenda Appendix C: Registered Attendees

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