The brain is undoubtedly one of the most complex organs within the human body. Not only does it control important bodily biochemical processes and actions, it also affects the way we process sensory information and perceive the world around us. The idea that you can “think yourself to healing” through belief and altered circumstantial perception has been widely researched in the medical community. A strong example of this is the placebo effect – a phenomenon where beneficial effects are experienced after a fake medical treatment. This effect, which relies on a strengthened mind-body connection, has shown to improve patient symptomatic outcomes both in clinical and non-clinical settings [1].
What is the mind-body connection?
The mind-body connection is the notion that your mind and body are not segregated systems - rather they work in cohesion with one another to interconnect one’s emotional and physical health [2]. According to Oakley Ray, Professor Emeritus of Psychology, Psychiatry and Pharmacology at Vanderbilt University, “there is no real division between mind and body because of networks of communication that exist between the brain and neurological, endocrine and immune systems.” This intimate interconnection of your mind and body means that your emotions, beliefs and thoughts can become physical - a major part of the placebo effect.
Imagine you’re preparing to perform in front of a large group of people. Thoughts such as “will I be able to hit that high note?” or “will people be impressed with me?” are likely to bombard you. Alongside these thoughts, your heart rate might skyrocket, your palms may begin to get clammy, and you may feel the need to go to the toilet. Urgently. This manifestation of your feelings into bodily sensations is a prime example of the mind-body connection.
What we believe we perceive - how does the placebo effect work?
It is still unclear what brain mechanisms are involved in generating the placebo effect, though many researchers believe it is a combination of patient expectation and classical/Pavlovian conditioning, which is a learned response through associations between different stimuli. Neuroimaging studies such as molecular neuroimaging utilising positron emission tomography and carfentanil (the selective µ-opioid receptor tracer) have assisted researchers in understanding the neurological mechanisms and pathways of the placebo effect [3]. From these studies, it is shown that, in general, many placebo responses stem from frontal cortical brain regions which relate to cognitive expectancies [4].
Patient expectation of how well a medical treatment/pill will work has been shown to directly influence the success of that treatment on the individual. One way this can be generated is through a supportive and positive interaction with the person administering your treatment. You trust your doctor, and the medication/treatment they have given you. This expectation of treatment success and emotions of hope and positivity impact the hormones, chemicals and neurotransmitters released around your body (a result of the mind-body connection). Some of these include endorphins, oxytocin [5] and the neurotransmitters dopamine and serotonin. As a result, this is interpreted by the patient as a healing effect with reduced symptoms.
Figure 1. A depiction of how expectation that placebo pain pills will help can change neurobiological signalling pathways to result in pain relief. [6]
A 2008 randomised-controlled trial conducted on patients suffering from irritable bowel syndrome explored three possible components that contributed to the placebo response and their magnitude on patient symptomatology. These components were: the assessment and observation of the patient, a therapeutic ritual (a validated sham acupuncture treatment), and a strengthened patient-clinician relationship. Participants were randomly placed into three groups: a “waiting list” group that did not receive any treatment, a “limited interaction” group where the placebo treatment was provided with limited clinician interaction and an “augmented interaction” group where the placebo treatment was applied with strengthened clinician interaction. The study concluded that the strongest placebo effect was experienced when patients had a strengthened relationship and supportive interaction with their clinician and that the placebo effect responses generated were of clinical importance. [7]
Figure 2. Outcomes at three week endpoint, with those in the augmented group (strengthened clinician interaction) reporting improved outcomes.
Pavlovian/Classical conditioning may also play a strong role in the placebo effect. Conditioned responses are a large part of our lives, as from a young age, we learn to make associations with the environment around us. Research has shown that an act as simple as popping a pill into our bodies can initiate a therapeutic effect in our bodies regardless of whether the pill was actual medication or not. This is due to past associations we have made with pills as a ‘healing method’ or cure. This effect works similarly to other medications such as ointments and balms due to associations with ointments as having a healing nature.
A 2006 randomized controlled study in patients with atopic dermatitis and healthy skin aimed to determine whether the placebo effect was achieved through expectancy or classical conditioning and which of these produced a stronger effect. 96 participants (48 that had atopic dermatitis and 48 with normal, healthy skin) were all prescribed a placebo ointment under the guise that it was a medically active ointment. To determine how much pain they were experiencing after their use of the ointment, an electric stimulus was applied to their skin. The results indicated that after application of the placebo ointment, there was a 50% reduction in the pain experienced from the electric stimulus. It was also noted that this positive effect seemed to be more prominent in individuals with atopic dermatitis compared to those with healthy skin. The study concluded that both expectancy and conditioning played a role in generating the placebo effect, but conditioning was vital to ensure the placebo effect lasted longer on the individual [8].
Healed through lies - Ethical issues with use of placebos in clinical settings
Ethics within the use of placebos in treatment have been widely explored and debated. As many placebos are medically inert and cannot guarantee therapeutic outcome for illnesses, they are sometimes viewed as deceptive and therefore considered unethical to be utilised in treatment. While informing the patient that their medication is a placebo doesn’t always mean the placebo effect won’t be felt [9] , continually doing this may result in ineffectiveness due to loss of conditioning and strengthened belief that the medication won’t work.
As placebos are unable to guarantee a positive patient outcome, this can be viewed as not upholding beneficence (prioritisation of patient welfare) in the healthcare setting. Beneficence in healthcare is critical as it ensures the healthcare provider is taking into account the patient’s individual situation so that the treatment outcome is the best possible option for them [10]. Prescribing a placebo to a cancer patient, over chemotherapy or other scientifically researched treatments is an example when the beneficence of the patient is not accounted for and would be considered extremely unethical. Not fully disclosing to the patient about what medication they have been prescribed, can also be viewed as violating the patient’s legal right to informed treatment consent [11]. This in turn, takes away the patient’s autonomy so they are unable to dispute a treatment/medication they believe won’t be beneficial to them.
Compared to modern medicine, not only are placebos still overall less effective in producing desired outcomes, their results are also unpredictable. This volatility in placebo treatment results render them unethical as the use of a placebo means the patient is denied scientifically researched medication which may be more likely to improve their condition. While placebos most probably won’t make their debut in the pharmaceutical world, there’s no denying their ability to stimulate the mind-body connection resulting in possible symptom improvement within ill individuals.
References:
[1] Wager TD, Atlas LY. The neuroscience of placebo effects: connecting context, learning and health. Nature Reviews Neuroscience [online]. 2015 Jun 19;16(7):403–18. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013051/
[2] Menezes L. What is the Mind-Body Connection? - Dr. Lakshmi Menezes [online]. Florida Medical Clinic. 2020. Available from: https://www.floridamedicalclinic.com/blog/what-is-the-mind-body-connection/
[3] Pecina, M. and Zubieta, J., 2018. Expectancy Modulation of Opioid Neurotransmission. Neurobiology of the Placebo Effect Part I, [online] 138, pp.17-37. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0074774218300163?via%3Dihub.
[4] Faria, V., Fredrikson, M. and Furmark, T., 2008. Imaging the placebo response: A neurofunctional review. European Neuropsychopharmacology, [online] 18(7), pp.473-485. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0924977X08000837?via%3Dihub.
[5] Skvortsova, A., Veldhuijzen, D.S., Pacheco-Lopez, G., Bakermans-Kranenburg, M., van IJzendoorn, M., Smeets, M.A.M., Wilderjans, T.F., Dahan, A., van den Bergh, O., Chavannes, N.H., van der Wee, N.J.A., Grewen, K.M., van Middendorp, H. and Evers, A.W.M. (2019). Placebo Effects in the Neuroendocrine System: Conditioning of the Oxytocin Responses. Psychosomatic Medicine, [online] 82(1), pp.47–56. Available from: https://www02.core.ac.uk/download/pdf/286390687.pdf.
[6] Pinch, B. and Choi, K. (2016). More Than Just a Sugar Pill: Why the placebo effect is real. [online] Science in the News. Available from: https://sitn.hms.harvard.edu/flash/2016/just-sugar-pill-placebo-effect-real/.
[7] Kaptchuk TJ, Kelley JM, Conboy LA, Davis RB, Kerr CE, Jacobson EE, et al. Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome. BMJ [online]. Available from: https://www.bmj.com/content/336/7651/999
[8] Klinger, R., Soost, S., Flor, H. and Worm, M., 2007. Classical conditioning and expectancy in placebo hypoalgesia: A randomized controlled study in patients with atopic dermatitis and persons with healthy skin. Pain, [online] 128(1), pp.31-39. Available from: https://journals.lww.com/pain/Abstract/2007/03000/Classical_conditioning_and_expectancy_in_placebo.7.aspx
[9] Lembo, A., Kelley, J., Nee, J., Ballou, S., Iturrino, J., Cheng, V., Rangan, V., Katon, J., Hirsch, W., Kirsch, I., Hall, K., Davis, R. and Kaptchuk, T., 2021. Open-label placebo vs double-blind placebo for irritable bowel syndrome: a randomized clinical trial. Pain, [online] 162(9), pp.2428-2435. Available from: https://journals.lww.com/pain/Abstract/2021/09000/Open_label_placebo_vs_double_blind_placebo_for.13.aspx.
[10] B, V., 2021. Principles of Clinical Ethics and Their Application to Practice. Med Princ Pract, [online] 30(1), pp.17-28. Available from: https://www.karger.com/Article/Abstract/509119#.
[11] Murray B. Informed Consent: What Must a Physician Disclose to a Patient? AMA Journal of Ethics [online]. 2008 Aug;14(7):563–6. Available from: https://journalofethics.ama-assn.org/article/informed-consent-what-must-physician-disclose-patient/2012-07
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