Placebos: Trick or Treat?

By Nellie Stidham

Artwork by Corinne Atkinson

Placebo: in Latin it means “I shall please.” In English, it is a greater medical phenomenon. The classic example of a placebo that is still used today is the sugar pill. In a randomized control study, half of the patients get a pill with a believed therapeutic effect while the others get a sugar pill. One may ask: why do you need a control? Can’t you just compare those with the drug with those not receiving anything? The short answer is no, and the long answer is what this article details. It is possible for placebos to be treatments within themselves. They work through a number of mechanisms, both psychological and biochemical.


The first is one many people are familiar with: classical conditioning. First described by Pavlov in 1902, this is a model of learning where two stimuli (i.e. food and a bell ring) are linked to produce a conditioned response (i.e. salivation), even in the absence of the unconditioned stimuli (i.e. food). Pavlov gave his dogs a stimulus in the form of food. The dogs had an unconditioned, or natural, response to salivate. In the experiment, this response was paired with the stimulus of a bell ringing, and over time the dogs would salivate due to the ringing of a bell alone, without the stimulus of food (Clark, 2004). The placebo effect works in a similar way. For many people, visiting a medical center has been paired with feeling better and improvements in health throughout their life, so the act can elicit a similar therapeutic effect without the active agent of a treatment.

Therefore, the stimuli of being in a hospital or taking pills every day can elicit a therapeutic response without an actual therapeutic agent (Benedetti, 2012).


Another mechanism believed to contribute to the placebo effect is based on how expectations affect reality. Pollo et al. (2001) ran a study with three arms looking at how much buprenorphine, a strong painkiller, was requested depending on how a standardized saline solution was characterized. For all three arms of the study, the patients were given exactly the same amounts of baseline painkillers. From here, the researchers either described the standardized saline solution as a powerful painkiller, told the patient that there was a 50% chance they received a powerful painkiller, or did not explain the contents of the saline solution. There was a statistically significant change in the amount of buprenorphine requested by the patients depending on the description of the saline they received. Those who were told the saline solution was a powerful painkiller requested 33.8% less buprenorphine than those who were not told anything about the saline. The patients’ expectations of their treatment dramatically changed the response seen without any change in administration (Pollo et al., 2001).


This is similar to studies that show patients’ desires, belief in self-efficacy, and anxiety impact pain scores (Benedetti, 2012). The “power of positive thinking”- could it possibly be more than a catchy inspirational saying? One study found that placebos activate the brain’s reward system, and with this activation there are positive health side effects. The presumed clinical benefit from a placebo may trigger this response and provide the body with therapeutic effects outside of the placebo’s expected mechanism (Benedetti, 2012). The brain’s reward system also has neurotransmitters that make people feel happy: endorphins. These are the body’s natural pain killers, and one study has shown that placebo believers have more than double the amount of endorphins in their cerebrospinal fluid than those of non-believers (Benedetti, 2012). These studies all show that patients’ beliefs and subconscious expectations impact outcomes with no difference in therapeutic treatments, positing that placebos do impact a patient's care and treatment plan.


In a less direct system, it was found that placebo-induced expectations of pain relief increased the level of proglumide (Benedetti, 2012). Proglumide is the antagonist of CCK, a neurotransmitter that modulates opiate tolerance in the brain. When patients underwent placebo treatments for pain, the amount of proglumide in the brain increased, which lowers the tolerance threshold for opioids, thereby allowing the same amount of opioids to have a greater effect on pain relief (McRoberts, 1986). Many different pathways mediate what is referred to as the placebo effect, however all of them have a common thread: they change the way pain is perceived by our bodies.

So, what is the placebo effect? Is it a treatment in itself? It depends on who you ask. All of these mechanisms contribute to the placebo effect, and there are probably many more that are yet to be discovered. Humans are complicated, and the power of the mind is often underappreciated. The way people think about a problem has many effects on the problem: it’s relative magnitude, the impact it has, and the way it is solved. Perhaps the power of positive thinking is actually based in biological mechanisms deep within our brains. Perhaps the treat(ment) lies within the trick.


References:

Benedetti, F. (2012, June). Placebo-Induced Improvements: How Therapeutic Rituals Affect the Patient’s Brain. JAMS Journal of Acupuncture and Meridian Studies. https://doi.org/10.1016/j.jams.2012.03.001


Clark, R. E. (2004). The classical origins of Pavlov’s conditioning. Integrative Physiological and Behavioral Science, 39(4), 279–294. https://doi.org/10.1007/BF02734167

McRoberts J. W. (1986). Cholecystokinin and pain: a review. Anesthesia progress, 33(2), 87–90.


Pollo, A., Amanzio, M., Arslanian, A., Casadio, C., Maggi, G., & Benedetti, F. (2001). Response expectancies in placebo analgesia and their clinical relevance. Pain, 93(1), 77–84. https://doi.org/10.1016/S0304-3959(01)00296-2

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