I earned my master's degree in the United States. When I was learning about the drug development process in a pharmacology class, the professor mentioned that the effect of a candidate drug in clinical trials must be better than the placebo effect. The placebo effect refers to a phenomenon where a patient's belief in a treatment, rather than the treatment itself, leads to therapeutic benefits.
In clinical trials, participants are randomly divided into two groups: one receives the candidate drug, while the other receives an inert placebo. All other conditions remain constant. If the condition of the first group significantly improves compared to the second group, this difference can be attributed to the candidate drug. Interestingly, symptoms often improve even in the placebo group. From a drug development perspective, it's crucial to design experiments that minimize the placebo effect and develop drugs that significantly outperform it.
Since I was listening to the class from a patient's perspective, I became curious about why medical practice does not strategically employ the placebo effect for treatment. From a patient's perspective, the source of improvementโwhether from the drug or the placebo effectโis irrelevant. After all, isn't the placebo effect essentially free? So I asked this question to the professor. He looked somewhat perplexed by this quirky question from an Asian student but he kindly did his best to convince me. His main point was that deceiving patients with an inert placebo is unethical.
Brain: The Bridge Between Body and Mind
Philosophers like Plato and Descartes, who have significantly influenced Western thought, believed that body and mind belong to entirely separate categories. This perspective of separating body and mind led to the placebo effect being viewed as a nuisance. In the 19th century, it was dismissed as patient deception, and in the 20th century, it was regarded as a temporary psychological effect. Only recently has the placebo effect gained recognition as a subject worthy of study.
The brain is part of the body yet closely tied to the mind. As a result, in conditions influenced by both the brain and mind, such as chronic pain, depression, and anxiety, the placebo effect tends to occur particularly strongly. This makes it more challenging to develop drugs that outperform the placebo effect for these conditions, to an extent that major pharmaceutical companies have reduced their research into neuropsychiatric medicines [1]. It is a surprising shift given the high revenue generated by drugs like Prozac for these disorders.
While the placebo effect poses a challenge in drug development, it's fascinating from a neuroscientific standpoint. It allows researchers to investigate how thoughts can affect the body and aids in developing new treatments. Researching the placebo effect is particularly important in neurological disorders, where the effects of medical treatments and placebos may overlap or interact.
The Placebo Effect
Context plays a crucial role in the placebo effect [2]. When patients are in a medical setting receiving professional advice, their expectation of improvement positively influences their symptoms. This effect can also be induced in animals through context learning. In one study, mice were given painkillers only when placed in a specific box. After several repetitions, researchers administered saline instead of the painkiller in the same box, and the mice's pain responses decreased as if they had received the actual painkiller, demonstrating that the placebo effect occurs in animals as well.
Information about the drug also influences the placebo effect. For instance, people showed a weaker placebo effect with fake drugs described as weak painkillers and a stronger effect with those presented as potent. This suggests that the magnitude of the placebo effect can be modulated based on prior information.
Researchers suggest that the prefrontal cortex, which interprets social context and anticipates outcomes, contributes to the manifestation of the placebo effect. It has also been proposed that the striatum, important in learning and predicting rewards, is associated with the positive effects and learning associated with the placebo effect. Variations in the size or activity of the striatum has been implicated with how strongly individuals experience the placebo effect. However, it's important to note that there isn't a single, uniform placebo effect; various placebo effects exist, and their neural mechanisms are only now beginning to be understood.
Body and Mind: Two Shadows of a Single Flame
While Western cultures have viewed body and mind as separate entities, this perspective isn't universal [3]. Some cultures, including East Asian ones, have seen the mind as rooted in the body and sought to cultivate the mind through physical practices. The brain, closely linked to the mind, interacts with the body through the nervous system and relies entirely on the energy and substances provided by the body. While breaking down complex subjects into smaller parts is a widely adopted approach to understanding them, dividing what is inherently indivisible might lead to confusion. Perhaps, the body and mind are like two shadows cast by a single flame of life on different walls.
Note Translated and transferred a column originally published in Kyunghyang Shinmun, a Korean national daily newspaper, on April 30, 2018.
References
Why 'big pharma' stopped searching for the next Prozac | Psychiatry | The Guardian
Wager TD & Atlas LY (2015) The neuroscience of placebo effects: connecting context, learning and health. Nature Reviews Neuroscience. (Link)
๋ฐ์ฐฌ์ฑ, ๊น์ข ์ฑ, ๊ฐ์ ์ต ๋ฑ (2009) ๋ชธ, ๋ง์๊ณต๋ถ์ ๊ธฐ๋ฐ์ธ๊ฐ ์ฅ์ ์ธ๊ฐ. ์ด์ฃผ์ฌ
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