The Neuroscience of Self-Healing: The Placebo Effect

Our bodies have an incredible capacity to heal after injury and disease. In clinical studies, healing without an actual medical intervention is called a placebo effect, and it often gets a bad reputation as "fake healing." But as the cartoon implies, not all placebo effects are equal, so this article is dedicated to understanding how our brains can promote recovery and why this could be a central component of NeuroCAM therapies. 


Our expectations shape our reality. While this folk wisdom has been around for generations, modern neuroscience has validated this statement to an extent. One theory of brain functioning suggests our brain is continuously generating expectations of what the world is like and slowly improving those expectations as we experience life 1. While this theory has mostly focused on things like visual perception, it could also apply to the experience of pain as well 2. Simply put, if you have a strong enough belief that you won't experience pain, then your brain will lessen your experience of pain. 

Of course, there are limits to this mind-over-matter placebo effect. To start, did you know that some people have stronger placebo effects than others? One cool study 3 used a (totally safe) muscle injection to make people experience pain and see how that experience changed when people did or did not receive a second placebo injection. Interestingly, people who were more "resilient", "agreeable", and less "neurotic" reported lower pain experiences after the placebo administration. Where this study gets cool is that this was all done in a brain scanner, and larger placebo responses were associated with higher levels of opioid neural activity. Painkiller medications (like Oxycodone) act on this opioid system, which naturally uses endorphins to lessen pain experiences. This means that not only did resilience-mindset people have a stronger placebo effect, but their brains released more endorphins to make their expectations reality. 

While the last study showed how personality could be related to the placebo effect, one's current mindset can also have an impact on this self-healing process. Since the brain communicates extensively with the immune system, one way scientists can study the placebo effect is by looking at reductions in the activity of the immune system after someone is given a placebo. One study did just this and found that at baseline, people with more active immune systems, people experiencing more anxiety, and people with higher levels of adrenaline (epinephrine for any British readers) all had larger suppression of the immune system from a placebo 4. While the previous study suggests that certain people are more likely to get placebo effects, this study suggests that certain mindsets can also activate the self-healing effects of a placebo. 

Main Points


Placebos activate opioid brain cells to change painful experiences

Some ways of enabling this self-healing brain process are better than others

So far, I have hoped to convince you that the placebo effect is not just some hocus-pocus, but an actual brain-based response that involves endorphins and the immune system. For some medical conditions, these changes could be just big enough to be an effective treatment. While I showed a couple of studies about how certain people and mindsets can instigate a placebo response, certain NeuroCAM treatments might be able to do precisely the same thing. Another cool study 5 also measured opioid activity using a brain scanner in fibromyalgia patients (a condition characterized by chronic pain), but instead of manipulating their expectations, they performed an acupuncture treatment. When the needles were correctly placed, they found the same kind of increased opioid activity as the previous placebo study I mentioned. Interestingly, this effect was not found when the needles were incorrectly placed, even though the patients were not able to guess whether they were received the real vs fake acupuncture treatment.

So does this mean acupuncture is technically nothing more than a placebo effect? Possibly. But, as the evidence shows, that doesn't mean it is any less real of a treatment. At the end of the day, what matters is that your body is engaged in the right processes to heal. If you experience chronic pain and an immunosuppressant drug can lower your experience of pain, that's objectively good for your health. So if acupuncture can also reduce your systemic inflammation by activating opioid pathways, why is it suddenly less of a treatment if its effects overlap with the placebo effect? In fact, one meta-analysis examining 9566 people in anti-depressant drug trials found that up to 67% of drug-responses could be attributable to placebo effects 6. So if 2/3 of a pharmaceutical treatment's effect is based on the activation of opioid pathways in the brain, then why not do all that you can to activate those neurons? Take the extra-strength fast-acting placebo and do all that you can to promote your brains' capacity for self-healing. 

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Ty the NeuroGuy

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Inspired By...

1. Huang, Y., & Rao, R. P. (2011). Predictive coding. Wiley Interdisciplinary Reviews: Cognitive Science2(5), 580-593.

2. Büchel, C., Geuter, S., Sprenger, C., & Eippert, F. (2014). Placebo analgesia: a predictive coding perspective. Neuron81(6), 1223-1239.

3. Peciña, M., Azhar, H., Love, T. M., Lu, T., Fredrickson, B. L., Stohler, C. S., & Zubieta, J. K. (2013). Personality trait predictors of placebo analgesia and neurobiological correlates. Neuropsychopharmacology38(4), 639. 

4. Ober, K., Benson, S., Vogelsang, M., Bylica, A., Günther, D., Witzke, O., ... & Schedlowski, M. (2012). Plasma noradrenaline and state anxiety levels predict placebo response in learned immunosuppression. Clinical Pharmacology & Therapeutics91(2), 220-226.

5. Harris, R. E., Zubieta, J. K., Scott, D. J., Napadow, V., Gracely, R. H., & Clauw, D. J. (2009). Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on μ-opioid receptors (MORs). Neuroimage47(3), 1077-1085.

6. Rief, W., Nestoriuc, Y., Weiss, S., Welzel, E., Barsky, A. J., & Hofmann, S. G. (2009). Meta-analysis of the placebo response in antidepressant trials. Journal of affective disorders118(1-3), 1-8.