What should I know about placebo?
Answer: Placebo, doesn’t mean no benefit.
Have you ever been offered to participate in a clinical trial or have a doctor explain to you the state-of-the art medication they have, only to be disappointed by hearing there’s a chance of you getting placebo? If you have, I really wish they explained in detail what a placebo is. If not, well here we go.
For the most part, people have used the word placebo to describe something that it’s not, a sugar-pill, to be bamboozled, to receive something that will bring no benefit, and it’s here where an important distinction should be made. There’s a difference between placebo and placebo effect.
Placebos are not implemented to contrast “receiving benefit” vs “not receiving benefit”, but rather “receiving benefit from the medication” vs “receiving benefit from the placebo”.
Yes, that’s right. Placebos can provide a benefit! This is one of the main reasons they need to be implemented. The investigators need to understand if their medication is having a greater benefit than the a placebo would. Now, how can placebos bring benefit?
A placebo is an inactive substance that looks like the drug or treatment being tested [1], there’s no argument there. But, the placebo effect, is a benefit received from a placebo. Although there are limitations on what a placebo effect do, it’s extremely common in psychiatry, pain management and neurology. Here’s an example:
During the Second World War, due to lack of resources, some wounded soldiers were injected with physiological saline solution in the absence of morphine [2]. Of course, the soldiers were not aware of this. But the mere thought of them receiving the medication would ease their pain.
Sure, not all of them received analgesia, and there’s no consensus on how long the benefit lasted, but the reality is that the prevalence of the placebo effect in pain ranges from 39 to 56%, estimating that intravenous administration of 1 ml of saline is equivalent to the analgesic effect obtained with 6–8 mg of intravenous morphine! [3]
How placebos work is still not quite understood, but it involves a complex neurobiological reaction that includes everything from increases in feel-good neurotransmitters, like endorphins and dopamine, to greater activity in certain brain regions linked to moods, emotional reactions, and self-awareness. [4]
The anticipation of receiving a benefit, can be strong enough to elicit a benefit. The placebo effect shows a remarkable variability between 7% and 49% of the treated patients [5]. This is part of the reason a placebo-control is needed. How else can we know if the medication is truly doing what it should?
Investigators should ensure that patients understand that clinical research is a heavily monitored activity and we can’t just have patients commit to suffering. Ensuring that patients receive a benefit and are safe is mandatory.
The best part, is that some trials even have alternatives to offer patients that were on a placebo. Among the most popular, is the “Open-Label” trials, which quite literally mean: You know exactly what you are receiving.
Having patients undergo a clinical trial can seem unnecessary. However, the closest we come to matching the experience of taking the actual medication, the higher the chance of having a benefit.
So, next time you are offered a clinical trial involving the use of placebos, don’t be disappointed. You never know the impact they may have on you!
References:
1- Placebos in clinical trials [Internet]. National Institute on Aging. U.S. Department of Health and Human Services; [cited 2023Mar30]. Available from: https://www.nia.nih.gov/health/placebos-clinical-trials#:~:text=A%20placebo%20is%20an%20inactive,treatment%20or%20occur%20by%20chance. trials#:~:text=A%20placebo%20is%20an%20inactive,treatment%20or%20occur%20by%20chance
2-Beecher HK. Pain in Men Wounded in Battle. Ann Surg. 1946 Jan;123(1):96-105. PMID: 17858731; PMCID: PMC1803463.
3-Benedetti F. Placebo and the new physiology of the doctor-patient relationship. Physiol Rev. 2013 Jul;93(3):1207-46. doi: 10.1152/physrev.00043.2012. PMID: 23899563; PMCID: PMC3962549.
4- The power of the placebo effect [Internet]. Harvard Health. 2021 [cited 2023Mar30]. Available from: https://www.health.harvard.edu/mental-health/the-power-of-the-placebo-effect
5- Breidert M, Hofbauer K. Placebo: misunderstandings and prejudices. Dtsch Arztebl Int. 2009 Nov;106(46):751-5. doi: 10.3238/arztebl.2009.0751. Epub 2009 Nov 13. PMID: 20019863; PMCID: PMC2795335.
