Open-label/non-deceptive placebos: Experimental design practice

[sue_frantz]

In doing some research on pain, I came across an open access journal article on an experiment that was testing the effectiveness of pain reprocessing.... Their control conditions were usual care and an open-label placebo (Ashar et al., 2022). An open-label placebo (aka non-deceptive placebo) is one where the study volunteers are told that they are being given a placebo. In that study, the placebo did confer some painkilling benefits, but the clear winner was pain reprocessing therapy. Yay! But what about this non-deceptive placebo business?

Here's another open access article that used a non-deceptive placebo (Guevarra et al., 2024). This experiment was on reducing depression, anxiety, and stress that were COVID-related. The researchers used the non-deceptive placebo as the experimental condition. The control condition received no treatment, just an assessment. “We hypothesized that the non-deceptive placebo intervention would reduce COVID-related stress, overall stress, anxiety, and depression compared with the control group” (Guevarra et al., 2024, p. 3). Their study took place in Spring 2021 when many places were still under COVID lockdown when COVID-related stress was common.

If you would like to give your students some experimental design practice either right after covering experiments in the research methods chapter or as an experimental design booster when you cover stress, give your students this hypothesis, and ask them to fill in a source of stress for students like themselves: “The non-deceptive placebo intervention would reduce [source of stress] stress, overall stress, anxiety, and depression compared with the control group.” The source of stress could be something like food insecurity, financial worries, or major exams. Really, anything students find stressful works.

Ask students to work in small groups to design an experiment that would test their hypothesis. Students should identify the independent variable and its levels and the dependent variable. They should also give consideration to where researchers conducting such a study would find volunteers. After discussion has subsided, invite a volunteer from each group to share the experiment their group designed.

For the COVID-stress study, researchers recruited participants on social media. Each participant was paid a total of $60 for completing all four sets of surveys (enrollment, baseline, midpoint, and endpoint). They only included adults who were experiencing COVID-related stress as measured by the COVID Stress Scale. Participants were randomly assigned to the control condition or to the non-deceptive placebo condition. Those in the non-deceptive placebo received information on what a non-deceptive placebo is and how effective they are. Since this study was conducted remotely, participants in this condition were sent placebos in the mail. The participants were instructed to take the pills for two weeks, one pill with breakfast and one pill with or after dinner.

Where does one get placebos, you ask? Amazon. For this study, researchers used Zeebo’s blue and white capsules. Zeebo markets themselves as “the world’s leading placebo brand.” Their placebos are considered a dietary supplement. I suppose they have to be something, and they’re clearly not a drug. The directions on the Zeebo bottle: “For bothersome symptoms. Take as needed.” Disclaimer: “You may or may not respond to placebo. Do not use Zeebo to replace or delay medical treatment.” And it was only after typing Zeebo four times did I finally realize it’s “placebo” without the “pla.” They’re not cheap at $24.45 for 45 capsules ($22.45 if you do ‘subscribe and save’). You can get a 30-count placebo pill made by a brand called Generic for $14.95. In short, expect to pay about 50 cents for each pill. Although the more expensive the placebo, the more effective it is (Díaz-Lago et al., 2023). Given that, I’d encourage Zeebo to add a more expensive placebo to their product line: Zeebo Extra Strength.  

The non-deceptive placebos were effective in reducing COVID stress, overall stress, anxiety, and depression. The control group also experienced decreases in all four measures, but the decreases for the participants in the non-deceptive placebo were much greater (Guevarra et al., 2024).

If you’d like to read more about non-deceptive placebos, here’s an open access review and meta-analysis from the journal Nature in 2023 (Spille et al., 2023).  

References

Ashar, Y. K., Gordon, A., Schubiner, H., Uipi, C., Knight, K., Anderson, Z., Carlisle, J., Polisky, L., Geuter, S., Flood, T. F., Kragel, P. A., Dimidjian, S., Lumley, M. A., & Wager, T. D. (2022). Effect of pain reprocessing therapy vs placebo and usual care for patients with chronic back pain: A randomized clinical trial. JAMA Psychiatry, 79(1), 13. https://doi.org/10.1001/jamapsychiatry.2021.2669

Díaz-Lago, M., Blanco, F., & Matute, H. (2023). Expensive seems better: The price of a non-effective drug modulates its perceived efficacy. Cognitive Research: Principles and Implications, 8(1), 8. https://doi.org/10.1186/s41235-023-00463-4

Guevarra, D. A., Webster, C. T., Moros, J. N., Kross, E., & Moser, J. S. (2024). Remotely administered non‐deceptive placebos reduce COVID‐related stress, anxiety, and depression. Applied Psychology: Health and Well-Being, aphw.12583. https://doi.org/10.1111/aphw.12583

Spille, L., Fendel, J. C., Seuling, P. D., Göritz, A. S., & Schmidt, S. (2023). Open-label placebos—A systematic review and meta-analysis of experimental studies with non-clinical samples. Scientific Reports, 13(1), 3640. https://doi.org/10.1038/s41598-023-30362-z