Can a placebo work when you know it is a placebo?

Yes, in some conditions. Researchers have run trials of so-called open-label or honest placebos, in which people are told the pill has no active ingredient, and a significant number of them report improvement. Harvard researcher Ted Kaptchuk says deception or concealment is not needed for a meaningful placebo effect in many conditions. Most trials so far are small, so the finding is promising rather than settled. Sources: [health.harvard.edu](https://www.health.harvard.edu/blog/placebo-can-work-even-know-placebo-201607079926) and [nationalgeographic.com](https://www.nationalgeographic.com/magazine/article/why-a-placebo-can-workeven-when-you-know-its-fake). [1] [2]

In a 2010 trial, 80 people with irritable bowel syndrome either received no treatment or took pills honestly described as being like sugar pills, with the word placebo printed on the bottle. After three weeks, 59 percent of the placebo group reported adequate symptom relief, against 35 percent of controls, according to the [news.harvard.edu](https://news.harvard.edu/gazette/story/2010/12/placebos-work-even-without-deception/) report. A later trial of 262 IBS patients added a conventional placebo group. After six weeks, the open-label and standard placebo groups had similar improvement, while the no-pill group did not change, as described by [nationalgeographic.com](https://www.nationalgeographic.com/magazine/article/why-a-placebo-can-workeven-when-you-know-its-fake). [3] [2]

A 2018 trial of 46 people with allergic rhinitis found that open-label placebos improved allergic symptoms more than no pills, with the effect appearing within a few days, according to [doi.org](https://doi.org/10.1371/journal.pone.0192758). A systematic review of 13 studies with nearly 800 participants concluded that open-label placebos showed significant positive effects, though the reviewers noted that positive studies are more likely to be published. [4] [2]

Placebos appear to act on symptoms that depend on self-observation, such as pain, nausea and fatigue. Kaptchuk says they cannot lower cholesterol or cure cancer, per [health.harvard.edu](https://www.health.harvard.edu/blog/placebo-can-work-even-know-placebo-201607079926). A paper on clinical trials makes the same distinction: placebo treatment is likely to relieve pain but will not shrink tumours, although subjective symptoms such as nausea, fatigue or hot flushes can be reduced ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC6888513/)). That paper also separates placebo responses, which include spontaneous improvement, from the placebo effect proper, which comes from psychobiological mechanisms tied to the therapeutic encounter. [1] [5]

The mechanism is not established. One idea, set out by Kaptchuk in the British Medical Journal in 2018, is that the brain can amplify pain and bodily sensations, and that being given an inert pill might interrupt that amplification. He says the uncertainty about whether it will work seems to matter, as reported by [nationalgeographic.com](https://www.nationalgeographic.com/magazine/article/why-a-placebo-can-workeven-when-you-know-its-fake). Another explanation is conditioning, as in a trial where a person paired a placebo capsule and a scent with opioids and later felt relief from the pairing alone. [2]

Positive expectation does not appear to be the driver. In the allergic rhinitis trial, inducing positive expectations did not change the primary symptom improvement, though it affected mental quality-of-life scores ([doi.org](https://doi.org/10.1371/journal.pone.0192758)). In the larger IBS trial, people who expected good results were less likely to improve with open-label placebos, a pattern not seen with standard placebos. A further suggestion, reported by [wired.com](https://www.wired.com/story/open-label-placebo-why-does-it-work/), is that feeling listened to and respected may contribute. [4] [2] [6]

The authors of the 2010 study called it small and limited, and said larger trials were needed ([news.harvard.edu](https://news.harvard.edu/gazette/story/2010/12/placebos-work-even-without-deception/)). The allergy trial had a short duration, no follow-up, only self-reported outcomes, and no closed-label comparison group ([doi.org](https://doi.org/10.1371/journal.pone.0192758)). [3] [4]