by Wayne Jonas
People with brain injury like Sergeant Martin get better during hyperbaric oxygen treatments, but not from the oxygen. See Miller, R., L. K. Weaver, N. Bahraini, et al. (2015). “Effects of hyperbaric oxygen on symptoms and quality of life among service members with persistent post-concussion symptoms: A randomized clinical trial.” Journal of the American Medical Association Internal Medicine 175(1): 43–52; and, Hoge, C. W. and W. B. Jonas, (2015). “The Ritual of Hyperbaric Oxygen and Lessons for the Treatment of Persistent Post-concussion Symptoms in Military Personnel.” Journal of the American Medical Association Internal Medicine 175(1): 53–54; and, Crawford, C., L. Teo, E. M. Yang, C. Isbister, and K. Berry (2016). “Is Hyperbaric Oxygen Therapy Effective for Traumatic Brain Injury? A Rapid Evidence Assessment of the Literature and Recommendations for the Field.” Journal of Head Trauma Rehabilitation (Open Access) doi:10.1097/HTR.0000000000000256.
CHAPTER 2: HOW WE HEAL
Over the last twenty to thirty years, researchers and practitioners have been repeatedly surprised at how large the improvement is in groups who are not getting an active treatment. Research on this effect—often called the “placebo effect” or “placebo response”—has grown tremendously. The best source of information on this sleeping giant in medicine is the database that is supported and maintained by the Society for Interdisciplinary Placebo Studies (SIPS). You can access this database (updated monthly) at: jips.online/.
A nice single summary of key research findings on the placebo response and its implications for healing can be found in the special journal issue: Meissner, K., N. Niko Kohls, and C. Luana (June 27, 2011). “Introduction to placebo effects in medicine: mechanisms and clinical implications.” Philosophical Transactions of the Royal Society of London Biological Sciences 366(1572): 1783–1789.
Other selected references readers may find of interest mentioned in this chapter include (in the order they are described):
Jonas, W. B., C. P. Rapoza, and W. F. Blair (1996). “The effect of niacinamide on osteoarthritis: A pilot study.” Inflammation Research 45(7): 330–334.
Franklin, B., Majault, L. Roy, Sallin, J. S. Bailly, D’Arcet, de Bory, J. I. Guillotin, and A. Lavoisier (2002). “Report of the commissioners charged by the king with the examination of animal magnetism.” International Journal of Clinical and Experimental Hypnosis 50(4): 332–363. A summary of Franklin’s investigation of Mesmerism—using blinded methods.
Beecher, H. K. (1955). “The powerful placebo.” Journal of the American Medical Association 159(17): 1602–1606. Posited that placebo accounts for about one-third of all outcomes.
Moerman, D. E. (2000). “Cultural Variations in the Placebo Effect: Ulcers, Anxiety, and Blood Pressure.” Medical Anthropology Quarterly 14(1): 51–72. Showed that placebo responses varied from 0% to 100% for the same treatment depending on the context, and not one-third, as Beecher claimed.
Kaptchuk, T. J., et. al. (2008). “Components of placebo effect: a randomized controlled trial in patients with irritable bowel syndrome.” The British Medical Journal 336(7651): 999–1003. Elegant study showing how the ritual delivers much of the placebo response.
Kaptchuk, T. J., E. Friedlander, J. M. Kelley, M. N. Sanchez, E. Kokkotou, J. P. Singer, M. Kowalczykowski, F. G. Miller, I. Kirsch, and A. J. Lembo (2010). “Placebos without deception: a randomized controlled trial in irritable bowel syndrome.” PLoS One 5(12): e15591. One of the first studies to show that telling people they were getting placebos did not significantly reduce their response.
Carvalho, C., J. M. Caetano, L. Cunha, P. Rebouta, T. J. Kaptchuk, and I. Kirsch (2016). “Open-label placebo treatment in chronic low back pain: a randomized controlled trial.” Pain 157(12): 2766. Confirmation of the above and showing clinically significant improvement for a major public health problem (back pain) from the placebo response—even when patients knew they were taking placebo.
For information about how placebo works in the brain, see the following three articles: Benedetti, F., H. S. Mayberg, T. D. Wager, C. S. Stohler, and J. K. Zubieta (2005). “Neurobiological mechanisms of the placebo effect.” Journal of Neuroscience 25(45): 10390–10402; and, Amanzio, M., et al. (2001). “Response variability to analgesics: a role for non-specific activation of endogenous opioids.” Pain 90(3): 205–215; and, Wager, T. D. and L. Y. Atlas (2015). “The neuroscience of placebo effects: connecting context, learning and health.” National Review of Neuroscience 16(7): 403–418. I also highly recommend the book by Professor Fabrizio Benedetti of the University of Turin, Italy, who is one of the world’s most renowned researchers on placebo. See Benedetti, Fabrizio. Placebo Effects. London: Oxford University Press, 2014.
It is not the placebo (the fake pill or treatment) that produces healing; it is the meaning that the ritual of treatment produces. See Moerman, D. E. and W. B. Jonas (March 19, 2002). “Deconstructing the placebo effect and finding the meaning response.” Annals of Internal Medicine 136(6): 471–476; and Jonas, W. B. (June 27, 2011). “Reframing placebo in research and practice.” Philosophical Transactions of the Royal Society of London Biological Sciences. 366(1572): 1896–1904.
There are now good sources for evidence summaries comparing treatments. These sources include the Cochrane Collaboration database, which can be found at cochrane.org. While Cochrane is an important site for finding evidence summaries from randomized controlled studies, they rarely do comparative reviews across treatments. Some good sources for comparative evidence reviews across treatments like the ones I did for Bill are BMJ Clinical Evidence Updates at clinicalevidence.bmj.com/x/set/static/cms/citations-updates.html; and The Agency for Healthcare Research and Quality EPC Evidence-Based Reports at www.ahrq.gov/research/findings/evidence-based-reports/index.html. Make sure your doctor has consulted one or more of these sources before he or she prescribes a treatment.
Personal engagement with the deeper aspect of yourself (especially social and emotional traumas) is profoundly healing. See, for example: Pennebaker, J. W. Opening Up: The Healing Power of Expressing Emotions. New York: Guildford Press, 1997; and, Smyth, J. M., A. A. Stone, A. Hurewitz, and A. Kaell (1999). “Effects of writing about stressful experiences on symptom reduction in patients with asthma or rheumatoid arthritis: a randomized trial.” Journal of the American Medical Association 281(14): 1304–1309.
Nondrug approaches to healing are gradually gaining evidence and mainstream emphasis, especially for pain. See, for example: Qaseem, A., T. J. Wilt, R. M. McLean, and M. A. Forciea (2017). “Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline from the American College of Physicians.” Annals of Internal Medicine 166(7): 514–530; and, Jonas, W. B., E. Schoomaker, K. Berry, and C. Buckenmaier III (2016). “A Time for Massage.” Pain Medicine 17(8): 1389–1390. doi:10.1093/pm/pnw086. Published online May 9, 2016; and, Crawford, C., C. Lee, C. Buckenmaier, E. Schoomaker, R. Petri, W. B. Jonas, and the Active Self-Care Therapies for Pain (PACT) Working Group (April 2014). “The Current State of the Science for Active Self-Care Complementary and Integrative Medicine Therapies in the Management of Chronic Pain Symptoms: Lessons Learned, Directions for the Future.” Pain Medicine 15: S104–S113. doi:10.1111/pme.12406.
CHAPTER 3: HOW SCIENCE MISSES HEALING
There is an ongoing debate in biomedical research about the role of what is called “reductionist” science, using approaches such as randomized, placebo-controlled trials (RCTs) as the primary type of evidence needed before accepting, using, and paying for treatments in practice. The importance of RCTs is clear, but their limitations are becoming more evident. Medical science is seeking better ways to collect evidence. For a good overall framing of the debate, see Federoff, H. J. and L. O. Gostin (2009). “Evolving from Reductionism to Holism: Is There a Future for Systems Medicine?” Journal of Internal Medicine 302(9): 994–996. See also notes for chapter 4 on systems science.
Other selected citations readers may find of interest mentioned in this chapter include the followin
g (in the order they are described):
Ayurveda is one of the oldest systems of healing in the world. The following chapter gives an excellent overview by one of the world’s leading practitioners. Lad, V. D. “Ayurvedic Medicine,” in Jonas, W. B. and J. S. Levin (eds.) Essentials of Complementary and Alternative Medicine. Philadelphia: Lippincott Williams & Wilkins, 1999; also see Chopra, A. and V. V. Doiphode (2002). “Ayurvedic medicine. Core concepts, therapeutic principles, and current relevance.” Medical Clinics of North America 86(1):75–89. Recent research at University of California, San Diego, and Chopra Center hints at the mechanisms that might explain Aadi’s recovery. See Mills, P. J., et al. (2016). “The Self-Directed Biological Transformation Initiative and Well-Being.” The Journal of Alternative and Complementary Medicine 22(8): 627–634.
Information on the global use of complementary, traditional, and integrative practices comes from the World Health Organization’s Office of Traditional Medicine at who.int/medicines/areas/traditional/en. The WHO defines traditional medicine as “the sum total of the knowledge, skills, and practices based on the theories, beliefs, and experiences indigenous to different cultures, whether explicable or not, used in the maintenance of health as well as in the prevention, diagnosis, improvement, or treatment of physical and mental illness.”
Cousins, Norman. Anatomy of an Illness as Perceived by the Patient: Reflections on Healing and Regeneration. New York: W. W. Norton & Co., 1979. One of the most clear and touching descriptions of how one man constructed his own healing journey.
The three-armed study led by Professor Jonathan Davidson of Duke, which showed that an herb, a proven drug, and placebo all worked the same for depression, can be found in Hypericum Depression Trial Study Group (2002). “Effect of hypericum perforatum (St. John’s Wort) in major depressive disorder: A randomized controlled trial.” Journal of Internal Medicine 287(14): 1807–1814. My commentary on how both professionals and the public missed the key issue for healing that this study revealed can be found in: Jonas, W. B. (2002). “St. John’s Wort and depression.” Journal of Internal Medicine 288: 446.
Little known to most people, replicability of scientific findings is a major problem in biology, psychology, and medicine. Most findings cannot be independently replicated. For a discussion and data on this issue see the following: Ioannidis, J. P. A. (2005). “Why most published research findings are false.” PLoS Med 2(8): e124; and, Ioannidis, J. P. (2017). “Acknowledging and Overcoming Non-reproducibility in Basic and Preclinical Research.” Journal of Internal Medicine 317(10): 1019–1020; and, Wallach, J. D., P. G. Sullivan, J. F. Trepanowski, K. L. Sainani, E. W. Steyerberg, and J. P. Ioannidis (2017). “Evaluation of Evidence of Statistical Support and Corroboration of Subgroup Claims in Randomized Clinical Trials.” Journal of Internal Medicine 177(4): 554–560; and, Prasad, V., A. Cifu, and J. P. A. Ioannidis (2012). “Reversals of Established Medical Practices: Evidence to Abandon Ship.” Journal of Internal Medicine 307(1): 37–38. Several groups are trying to address this issue. See a summary of those efforts in Yong, E. (August 27, 2015). “How Reliable are Psychology Studies?” The Atlantic.
Partly because of the above, the overuse of unproven treatments and treatments proven not to work is large—likely one-third of everything done in medicine. To remedy this, guidelines for stopping treatments that are often used but known to harm or not help can be found at choosingwisely.org/about-us. I suggest reviewing any treatments you are doing with your doctor using this site to see what you can stop doing.
For a nice summary of the decline effect and problems with scientific validity see Lehrer, J. (December 13, 2010). “The truth wears off: Is there something wrong with the scientific method?” The New Yorker. For even more detail on why this happens, see the book by Richard Harris, science reporter for PBS, called Rigor Mortis: How Sloppy Science Creates Worthless Cures, Crushes Hope, and Wastes Billions. New York: Basic Books, 2017.
The information for the statin graphic in this chapter comes from Redberg, R. F. and M. H. Katz (2016). “Statins for Primary Prevention: The Debate Is Intense, but the Data Are Weak.” Journal of Internal Medicine 316(19): 1979–1981.
Evidence-based medicine is not as accurate as most people think. Pulitzer Prize–winning author Siddhartha Mukherjee eloquently describes the uncertainty of science and the challenge of using science for making decisions in medicine. See Mukherjee, Siddhartha. The Laws of Medicine: Field Notes from an Uncertain Science. New York: Simon and Schuster, 2015.
CHAPTER 4: A SCIENCE FOR HEALING
There is a need to build better science and information models to address the limitations of the reductionist approach described in chapter 3. In the 1960s, this was called the “biopsychosocial” model of medicine and became the foundation for the specialty of family medicine—the specialty I practice. More recently, what I call “whole systems science” is being fed by large-scale efforts for using “big data” sets drawn from daily health care delivery and linking this data with the basic biomarkers of disease and health—at cellular, chemical, and genetic levels—and then linking that to people’s activities, experiences, and long-term health outcomes. It is a big task. The largest ongoing scientific effort in this is the one-million person study by the National Institutes of Health called the Precision Medicine Initiative. See allofus.nih.gov/. For summaries of whole systems and complexity science in primary care, complementary medicine, and implementation science, see the following three references:
On primary care: Sturmberg, J. P., C. M. Martin, and D. A. Katerndahl (2014). “Systems and Complexity Thinking in the General Practice Literature: An Integrative, Historical Narrative Review.” Annals of Family Medicine 66–74.
On complementary medicine: Verhoef, M., M. Koithan, I. R. Bell, J. Ives, and W. B. Jonas (2012). “Whole Complementary and Alternative Medical Systems and Complexity: Creating Collaborative Relationships.” Forschende Komplementärmedizin 19(Suppl 1): 3–6. This entire issue is about the application of whole systems science to complementary medicine.
On health care delivery: Leykum, L. K., H. J. Lanham, J. A. Pugh, M. Parchman, R. A. Anderson, B. F. Crabtree, P. A. Nutting, W. L. Miller, K. C. Stange, and R. R. McDanie (2014). “Manifestations and implications of uncertainty for improving healthcare systems: an analysis of observational and interventional studies grounded in complexity science.” Implementation Science 9(165): 2–13.
Other selected references of interest include (in the order topics are addressed):
Price, D. D. (2015). “Unconscious and conscious mediation of analgesia and hyperalgesia.” Proceedings of the National Academy of Sciences of the United States of America 112(25): 7624–7625. What your doctor believes influences your healing response.
Frank, Jerome and Julia Frank. Persuasion & Healing. Baltimore: Johns Hopkins University Press, 1961. A classic on the influence of healers on those seeking treatment.
Walach, H. and Jonas W. B. (2004). “Placebo research: The evidence base for harnessing self-healing capacities.” The Journal of Alternative and Complementary Medicine 10(Suppl 1): S103–S112. Outlines a roadmap for healing by examining placebo research.
de Craen, A. J., D. E. Moerman, S. H. Heisterkamp, G. N. Tytgat, J. G. Tijssen, and J. Kleijnen (1999). “Placebo effect in the treatment of duodenal ulcer.” British Journal of Clinical Pharmacology 48(6): 853–860. Outcomes vary for the same treatment depending on where the treatment is delivered (home or hospital), the number of pills (two or four per day), and the color of the pills.
Ader, R. and N. Cohen (1975). “Behaviorally conditioned immunosuppression.” Psychosomatic Medicine 37(4): 333–340. Professor Ader’s breakthrough work showed that animals could learn how to alter their own immune system and live longer. This has also now been shown in humans.
The idea that small doses of toxins (or any stimulant) can induce healing is extensively documented in science but not widely known or applied in medicine. The best source of information on this is the Internatio
nal Dose-Response Society led by Edward Calabrese and colleagues at the University of Massachusetts, Amherst. See the peer-reviewed journal Dose-Response at dose-response.org for access to this extensive scientific field. Professor Calabrese’s database is an encyclopedic source of scientific information showing how toxic substances from oxygen to stressful behaviors such as fasting and exercise can induce protective and reparative responses that lead to healing. See the three articles below for summaries on general mechanisms and how this works in exercise and fasting.
On the biological mechanisms: Calabrese, E. J. (2013). “Hormetic mechanisms.” Critical Reviews in Toxicology 43(7): 580–606.
On exercise: Ji, L. L., J. R. Dickman, C. Kang, and R. Koenig (2010). “Exercise-induced hormesis may help healthy aging.” Dose-Response 8: 73–79.
On fasting: Mattson, M. P. and R. Wan (2005). “Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems.” The Journal of Nutritional Biochemistry 16(3): 129–137.
Since most of us are overstimulated psychologically, removal of that stimulation through relaxation allows healing on the clinical, physiological, and genetic levels: See the classic work by Benson, Herbert and Miriam Z. Klipper. The Relaxation Response. New York: HarperCollins, 1992. Also see Dusek, J. A., H. H. Otu, A. L. Wohlhueter, M. Bhasin, L. F. Zerbini, M. G. Joseph, H. Benson, and T. A. Libermann (2008). “Genomic counter-stress changes induced by the relaxation response.” PloS One 3(7): e2576; and, Bhasin, M. K., J. A. Dusek, B. H. Chang, M. G. Joseph, J. W. Denninger, G. L. Fricchione, H. Benson, and T. A. Libermann (2013). “Relaxation response induces temporal transcriptome changes in energy metabolism, insulin secretion and inflammatory pathways.” PLoS One 8(5): e62817.