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Neurobiological Effects and Mechanisms

Introduction and Explanation of Need

Complementary and integrative health approaches have been commonly used by the general public to treat or manage disorders or symptoms relevant to the nervous system. These range from pain, sleep disturbance, stress, anxiety, and behavioral disorders to more serious neurological or mental health conditions. Commonly used complementary health approaches include mind and body interventions such as meditation, spinal manipulation, yoga, massage, tai chi, and acupuncture. A variety of natural products, including herbs, dietary supplements, and prebiotic or probiotic products are also commonly used. Despite their broad usage by the general public, the therapeutic benefits of these approaches are, at best, modest and often not significantly better than placebo when subjected to rigorous efficacy studies. In-depth understanding of the mechanisms by which complementary and integrative health approaches may impact physiological systems, including the central nervous system, becomes critical for developing strategies to optimize the beneficial effects of these approaches.

Whether and how complementary health approaches directly modulate or modify the structure and/or function of the entire or part of the nervous system and other associated physiological systems such as organs and tissues, remains understudied. Such studies are scientifically challenging for both the complementary and integrative health and the biomedical research communities. This challenge is further compounded by individual differences (e.g., genetic and epigenetic differences, psychosocial and environmental factors). Nevertheless, recent transformative advances in genomics, neuroscience, stem cells, systems biology, neuroimaging, and predictive computational modeling offer excellent technological and conceptual resources and opportunities for innovative and impactful mechanistic studies of complementary health approaches.

What Does Success Look Like?

Successful mechanistic studies of complementary and integrative health approaches include two separate but interoperable accomplishments in model systems/organisms and/or human/clinical populations:

  • Identification of modifiable mechanisms of complementary health approaches that may optimize the beneficial effects of these approaches alone or in combination with other therapies.
  • Identification of predictive mechanisms or biomarkers that can differentiate responders from nonresponders to these approaches.


  • Develop or utilize innovative (1) humanized cellular or organ systems or (2) transgenic or preclinical animal models to investigate neural mechanisms of complementary and integrative health approaches.
  • Ascertain the sensory neural basis or anatomical and physiological pathways of acupoints in various forms of acupuncture, acupoint-based stimulation interventions, or manual therapies in animal models or human subjects.
  • Determine and analyze the neural pathways by which acupuncture, acupoint-based stimulation interventions, or manual therapies such as massage, exert their analgesic effects or therapeutic effects on various physiological systems (e.g., immune system, vascular system, musculoskeletal system, or internal organs such as brain, heart, and gut) in animal models or human subjects.
  • Investigate top-down neural pathways underlying the effects of meditation, expectancy, placebo effects, and other mindfulness interventions (i.e., meditative yoga, tai chi, qi gong, hypnosis, and guided imagery), ranging from high-order brain functional regions to the peripheral tissues and organs such as immune cells, gut, muscles, bone, heart, and microbiome.
  • Assess the neural pathways or other physiological mechanisms by which meditative movement and related therapies impact the structure and function of the central nervous system.
  • Examine innovative neural mechanisms by which candidate natural products such as cannabinoids and some Chinese Traditional Medicine herbs or patches, generate analgesic effects.
  • Pilot test neural mechanistic effects of combined natural products and mind and body interventions for acute and/or chronic pain management, other symptom management, or behavioral change.

Areas of Low Programmatic Priority

  • A replicative mechanistic study of complementary and integrative health approaches in different clinical populations.

Top Scientific Priorities