I sometimes share speculative ideas on ethical placebo use that might help guide future research. In my 2014 book The Placebo Cure: And Other Mind Body Effects, I outlined research concepts related to pain symptom management, reducing the risk of post-surgical opioid dependency, and supporting medication tapering through honest placebo use.
My intention in sharing these thoughts publicly is to contribute to research discussions and help shape agendas for investigator-initiated studies. Meanwhile, our ethical placebo, Zeebo Relief, has already been used in several such studies published in peer-reviewed journals. Topics included chronic pain management, exam-related stress relief, and remote anxiety interventions during the pandemic.
Lately, I’ve thought about how clinical research could explore ways in which honest placebos might support patients during the tapering of antacid medications, such as proton pump inhibitors (PPIs), once the underlying condition has resolved.
The issue of long-term antacid use is common in the U.S. and affects millions of people. For context:
• The use of prescription PPIs doubled from 4.1% of U.S. adults in 1999–2000 to 8.6% in 2017–2018 (Bergin et al., 2023).
• Reviews suggest that 30-60% of long-term PPI users may no longer have a clear medical indication for continued use but still struggle to stop, often due to symptom recurrence (Haastrup et al., 2014; Forgacs & Loganayagam, 2008).
• Clinical studies have shown that rebound acid hypersecretion can occur after discontinuing PPIs—even in people without prior symptoms. For example, in a controlled trial, 44% of previously asymptomatic participants developed acid-related symptoms after 8 weeks of PPI use, despite no history of GERD (Reimer et al., 2009). This rebound effect does not occur with placebo.
This raises an important research question:
Could honest placebo use reduce the risk of PPI dependency and facilitate safe discontinuation once the original medical need has resolved?
A possible study protocol could follow the logic of opioid tapering research. After a physician has determined that PPI therapy is no longer medically necessary, participants could be invited into a tapering study where they receive both a gradually reduced PPI dose and an honest placebo. Over time, participants could be encouraged to shift toward increased placebo use, in a structured and transparent way. The hypothesis is that this substitution could modulate psychological dependency and improve success rates of discontinuation. More timely tapering off would lead to reduced rebound frequency, duration, and intensity.
Such an approach might be strengthened by complementary interventions. For example, during the tapering period, the U.S. Department of Veterans Affairs recommends techniques like deep breathing and mindfulness to support medication reduction. These behavioral tools, outlined in VA’s Power of the Mind and Mindful Awareness Whole Health overviews, might synergize with placebo effects in easing the transition off PPIs.
This is a research concept. I believe it deserves exploration, given how widespread long-term PPI use has become and how difficult discontinuation can be. An honest placebo study, designed with full transparency and proper clinical oversight, could offer new pathways for easing patients off medications when the time is right.
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References
• Forgacs I, Loganayagam A. Overprescribing proton pump inhibitors. BMJ. 2008 Jan 5;336(7634):2-3. doi: 10.1136/bmj.39406.449456.BE. PMID: 18174564; PMCID: PMC2174763.
• Haastrup PF, Thompson W, Søndergaard J, Jarbøl DE. Side Effects of Long-Term Proton Pump Inhibitor Use: A Review. Basic Clin Pharmacol Toxicol. 2018 Aug;123(2):114-121. doi: 10.1111/bcpt.13023. Epub 2018 May 24. PMID: 29658189.
• Reimer C, Søndergaard B, Hilsted L, Bytzer P. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology. 2009 Jul;137(1):80-7, 87.e1. doi: 10.1053/j.gastro.2009.03.058. Epub 2009 Apr 10. PMID: 19362552.
• Bergin E, Zylberberg HM, Lebwohl B, Freedberg DE. Trends in use of proton pump inhibitors among adults in the United States from 1999 to 2018. Pharmacoepidemiol Drug Saf. 2023 Dec;32(12):1406-1410. doi: 10.1002/pds.5676. Epub 2023 Jul 31. PMID: 37524589.
• Björnsson E, Abrahamsson H, Simrén M, Mattsson N, Jensen C, Agerforz P, Kilander A. Discontinuation of proton pump inhibitors in patients on long-term therapy: a double-blind, placebo-controlled trial. Aliment Pharmacol Ther. 2006 Sep 15;24(6):945-54. doi: 10.1111/j.1365-2036.2006.03084.x. PMID: 16948806.
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Disclaimer
This article presents speculative ideas for future research on ethical placebo use. It is not intended as medical advice, and nothing herein should be interpreted as a recommendation to start, stop, or change any medication. Always consult a licensed healthcare provider before making decisions about medical treatment.