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Objective 1: Advance Fundamental Science and Methods Development


Fundamental scientific inquiry is essential to the progress of biomedicine by enhancing the understanding of how living systems work. This understanding serves as a foundation for translational and clinical studies that can lead to improved approaches to the management, treatment, and prevention of diseases and symptoms.

Fundamental science plays a key role in fulfilling NCCIH’s mission. The Center provides strong support for basic and mechanistic research on complementary health approaches. NCCIH’s basic research is aimed at understanding the nature of complementary health approaches such as their biology, physiology, and physical, chemical, and behavioral properties. NCCIH also supports the development of tools, models, and methodologies for studying these approaches. NCCIH’s mechanistic research is focused on identifying and understanding the active components of a complementary health approach and how those components produce effects. Depending upon the question, basic and mechanistic studies may be performed in vitro, in animals, or with human volunteers.

NCCIH also supports research studies characterizing the active elements of complex interventions. These studies often require multidisciplinary expertise and frequently use state-of-the-art techniques in areas such as neuroscience, immunology, pharmacognosy, proteomics, genetics, and epigenomics. Understanding the mechanisms by which complex complementary or integrative interventions exert their effects is critical for the development of optimized interventions.


1. Advance understanding of basic biological mechanisms of action of natural products, including prebiotics and probiotics.

NCCIH has a broad interest in studying the biological activities of natural products, including the potential effects of these products on a variety of clinical conditions, and their potential to promote wellness or resilience. Many of the natural products used in this context are very complex, with multiple molecular constituents that may contribute to their effects. To fully understand the activity of a complex product, it is necessary to identify the individual components responsible for a specific activity and determine how those components interact with other components. Preclinical model systems are valuable for these studies.

Going forward, NCCIH will continue to sponsor research on compounds isolated from natural products, as well as on the complex mixtures from which they originate. Future studies may focus on both the beneficial and harmful effects of natural products, including their interactions with medications. NCCIH-funded studies may also include the characterization of novel natural products or their chemical constituents.

Additionally, NCCIH will continue to support research to elucidate the effects of probiotics and prebiotics on the microbiota naturally present in the human body. NCCIH seeks to address fundamental knowledge gaps, including those pertaining to microbiota molecular mechanisms of action and potential interactions with pre- and probiotics and their impact on processes in the human body. The Center is interested in research on the role of gut microbiota and the potential for pre- and probiotics to modulate gut microbiota. This research may provide a sound basis for developing probiotic and prebiotic products that can enhance or restore health, including disorders that may be associated with the brain-gut axis (e.g., pain and anxiety). NCCIH aligns its probiotics research program with trans-NIH microbiome initiatives such as the Human Microbiome Project. NCCIH will continue to work closely with other NIH Institutes, Centers, and Offices; the Food and Drug Administration; and the United States Department of Agriculture to leverage its investments in this research area.

2. Advance understanding of the mechanisms through which mind and body approaches affect health, resiliency, and well-being.


Mind and body approaches such as meditation, spinal manipulation, massage, yoga, tai chi, hypnosis, and acupuncture, are being studied for their effects on a variety of symptoms and on resiliency and well-being. To design and carry out rigorous clinical research on these approaches, it is important to have insight into their biological effects and the mechanisms of action by which these approaches impact physiology. Going forward, NCCIH investments will emphasize fundamental research to advance the understanding of the mechanisms through which mind and body approaches affect health.

An important focus of research on mind and body interventions is the central nervous system—the brain and spinal cord. NCCIH seeks to advance research aimed at elucidating the effects of interventions such as meditation and acupuncture on central mechanisms of pain perception, processing, and control. In addition, the Center also is interested in how factors such as emotion, attention, the environment, and genetics affect pain perception.

Studying how mind and body approaches affect the nervous system is scientifically challenging. This challenge is compounded by individual variability attributable to genetic, epigenetic, and environmental differences. Nevertheless, recent advances in genomic science, neuroscience, stem cell research, systems biology, neuroimaging, and predictive computational modeling offer excellent resources and opportunities for neural mechanistic studies of complementary health approaches.

3. Develop new and improved research methods and tools for conducting rigorous studies of complementary health approaches and their integration into health care.


Rigorous research on complementary health approaches requires well-established methodology, including valid, reliable, and relevant research tools and outcome measures. NCCIH seeks to support fundamental science that will lead to the development of improved methodologies for complementary health research, especially those that can be used to assess symptoms such as pain, depression, and anxiety. Studies that identify and validate objective endpoints or biomarkers, assess and measure adherence or treatment fidelity, or will otherwise strengthen the design of clinical trials of complementary health approaches are particularly important.

  1. Catalyze advances in natural products methodology

    Natural products have a long and impressive history as sources of medicine and as important resources for biological research. However, many of the techniques for studying complex mixtures of natural products have remained unchanged for many years and have yet to leverage advances in biological and chemical methodologies.

    To move the field forward, NCCIH is placing a renewed emphasis on overcoming methodological and technological hurdles that hinder advances in natural products research. For example, “omics-based” and other high-throughput technologies may help researchers evaluate the validity of hypothesized additive or synergistic effects that are at the core of many traditional herbal medicines. In addition, the use of network pharmacology—the study of the web of biologic targets for any bioactive substance—will enable researchers to investigate the complex effects of natural products on multiple targets in ways that were never before possible.

  2. Support development of novel technologies and instruments, including diagnostic methods, tools, and sensors.

    To carry out rigorous research on symptom management and functional changes, scientists need valid, reproducible ways to assess symptoms.

    • Biosensors and Mobile Health: Rapid advances in technology and bioengineering are facilitating the development of increasingly sophisticated and versatile sensors. These sensors should enable improved reporting of symptoms and functional outcomes, as well as contribute to improved data capture. For example, wearable biosensors such as bracelets, patches, and caps can collect data on movement and physical activity, blood sugar levels, heart rates, and neural activity.
    • Patient-Reported Outcomes: Patient Reported Outcomes Measurement Information System (PROMIS) tools are well suited for use as endpoints in clinical studies on the effectiveness of treatment. Further refinement and testing of PROMIS and other patient-reported outcome tools will lead to improved ways to assess pain, depression, anxiety, and other symptoms not easily measured with other diagnostics.
    • Imaging and Neurotechnologies: Improved methods and tools are needed to understand the neurological aspects of symptoms such as pain, depression, and anxiety. Advances in imaging and other neurotechnologies may provide an improved means of measuring and understanding the neurologic circuits that underlie symptoms. For example, electrophysiological recordings, single photon emission computed tomography (SPECT), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI) show promise for advancing what is known about neurologic and other biologic factors associated with pain and other symptoms. With NCCIH’s participation, some of these advances may be realized through the NIH B.R.A.I.N. (Brain Research through Advancing Innovative Neurotechnologies®) initiative.
    • Biomarkers: There is an urgent need for the identification of biomarkers that can be used to assess pain and other symptoms. Advances in high-throughput technology and bioinformatics are providing new tools to simultaneously measure many metabolites, thus facilitating the identification of metabolites and other molecules associated with changes in symptom severity and functionality.