Honest placebos and their implications in naturopathic medicine

Jacob Schor

Here is an idea to chew on:

Let’s start by describing an study published in 2010, a paper whose lead author, Ted Kaptchuk, should be familiar to our older doctors as his 1983 book, The Web That Has No Weaver, served as a textbook in Chinese Medicine during our naturopathic training.  

Kaptchuk reported the results of a clinical trial he conducted at Harvard Medical School on patients with irritable bowel syndrome (IBS).  Eighty patients (70% female) were recruited between August 2009 and April 2010, mean age 47, diagnosed with IBS via Rome III criteria and with a score ≥ 150 on the IBS Symptom Severity Scale. 

 “Patients were randomized to either open-label placebo pills presented as ‘placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes’ or no-treatment controls….The primary outcome was IBS Global Improvement Scale (IBS-GIS). Secondary measures were IBS Symptom Severity Scale (IBS-SSS), IBS Adequate Relief (IBS-AR) and IBS Quality of Life (IBS-QoL).” 

The patients who received the open-label placebo, even though they knew they were being treated with nothing, improved significantly.  Global improvement scores (IBS-FIS) were significantly better both at 11 days (study midpoint) and at 21 days (study endpoint), (5.0 ± 1.5 vs. 3.9 ± 1.3, p = .002).  Symptom severity was also significantly reduced at these same time points.¹ 

To understand why Kaptchuk’s study is important, we need back up nearly six decades and consider certain events that put this study into perspective. 

The first clinical trials demonstrating placebo effects are real were published in the 1950s.  Henry Beecher’s 1955 paper, “The Powerful Placebo” published was the landmark paper that made placebo effect a legitimate phenomenon; it  remains the most often cited paper on placebo. Beecher reported that in a series of fifteen trials he had conducted, 35% of 1,082 patients experienced satisfactory symptom relief via placebo.² Since then, the placebo effect has been considered a scientific reality. Beecher’s paper was also the turning point in medicine after which an expectation developed that any drug worthy of use in clinical practice had to beat a placebo at symptom relief. Drugs had to be better than nothing. There is a certain “irony that just when the effectiveness of placebo treatments was quantitatively proven, forcing this new design into clinical research, they stopped being used clinically as therapeutic agents.” ³ 

Yet during the next fifty years, although we’ve evaluated drug action against placebo action, there has been a paucity of research looking directly at placebo.  Where did our hesitancy to use placebos to treat symptoms originate?

To understand medicine’s hesitation, step further back from Beecher just a few years to the late 1940s and consider the impact of the Nuremberg Trials, specifically the Doctors’ trials. 

From December 1946 to August 1947, twenty-three Nazi doctors were prosecuted at Nuremberg for war crimes and crimes against humanity. The charges included lethal experiments and the euthanasia program that was part of the eugenics program by which the Nazis hoped to create a master race. 

These doctors had systematically developed a poison gas used to kill approximately 250,000 to 300,000 people who had physical or mental disabilities or who suffered from chronic illness.  The techniques they developed were later used during the Holocaust to kill millions more people. 

Reading about these doctors in the newspapers turned people’s stomachs

The initial defense strategy employed by the German doctors was that they had ‘broken no rules’ in doing what they had done.  To counter this defense the Nuremberg Court spelled out a list of ten rules of ethical conduct for human experimentation that doctors were expected to adhere to that are now known as the Nuremberg Code.

The Nuremberg Code does not specifically prohibit or even mention use of placebo, yet, two of the rules were quickly interpreted to do so limiting placebo use.  Rule 1: “voluntary consent” requires that participants in a human trial have ‘sufficient knowledge and comprehension of the experiment.  This means that researchers need to explain that a participant might receive a placebo instead of the active treatment. Rule 4: “Avoid unnecessary suffering” is interpreted that placebo can’t be used in place of a known effective treatment to create a control group.

These limitations on placebos were reinforced in 1964 by the Declaration of Helsinki (specifically Article 33), that prohibits placebo use if a "best proven intervention" already exists, except in very specific circumstances. The U.S. Food and Drug Administration effectively began requiring placebo-controlled trials for new drugs in 1962. While medicine has acquired a great deal of data from comparing drugs against placebo, there has been great hesitancy to actually research placebo directly.  Most medical associations, including the American Medical Association, continue to strongly discourage placebo use outside of controlled clinical trials.  

To prescribe a placebo, a doctor must deceive the patient, so placebo use must involve deception, which violates patient autonomy and can erode trust: to put it simply, doctors should not lie.   The “American Medical Association (AMA) holds that purposefully using placebos for their effect in clinical care is unethical unless the patient’s consent is obtained. ”⁴  Or at least this is what everyone believed until Kaptchuk’s IBS study was published. 

Kaptchuk was hired by Harvard University in 1990 to determine to what degree alternative medicine was real and how much was just placebo.  To accomplish this, he realized that a far better understanding of placebo action was necessary.  He has spent the years since looking at placebo effects; he is now the Director of Harvard Medical School’s Program in Placebo Studies.

Ted Kaptchuk’s 2010 study is often described as the first clinical trial of non-deceptive placebos.  [A careful search does find two earlier open-label placebo trials, Lieberman in 1962 and Park in 1965. ⁵ ⁶] Kaptchuk’s placebos were prescribed honestly, without deception.  That means the patients were clearly informed they were not getting any real medicine.  The bottles were even labeled “placebo.” Their use didn’t break any ethical taboos, Nevertheless, the placebos proved effective.  

Ruminate on that for a bit

Prior to this, we all assumed that placebo effect hinged on the patient’s belief that the medicine was real and their symptoms improved as a result of belief: an effective drug wasn’t necessary.  These results told us that belief is not even necessary.  Kaptchuk’s results with IBS, though not easy to swallow, have been confirmed in the years since by Bailou in 2017⁷ and 2022⁸, Lembo in 2021⁹, and Wang in 2022.¹⁰

Note that in Lembo’s 2021 study open-label placebo (OLP) was also compared against a double-blind placebo (DBP) and against a no-pill control group.  The mean improvement on the IBS Severity Scoring System at 6-weeks was significantly greater for both of the placebo groups than for the no pill control group (90.6 vs 52.3, P = 0.038). OLP and DBP did not differ significantly on IBS Severity Scoring System improvement (100.3 vs 90.6, P = 0.485).  “Open-label placebo and DBP had similar effects that did not differ significantly, suggesting that blinding may not be necessary for placebo.”

We should consider Kaptchuk’s results knowing that IBS does seem particularly susceptible to placebo.  A 2010 meta-analysis by Ford and Moayyedi examined studies of placebo response in IBS. They identified 73 randomized controlled trials from which to draw data. Of the 8,364 IBS patients who received placebo, 37.5% responded (95% CI 34.4-40.6%).¹¹  

While pondering these numbers, consider the results of an earlier Kaptchuk study from 2008, two years prior to his open-label placebo and IBS study was published.  In the earlier study all patients had IBS, yet none received actual treatment. They were divided into three groups.  One group was put on a waiting list to serve as the control group.  The other two groups received sham acupuncture but which differed between groups in how the practitioner behaved toward the patients.  In one group, the practitioner limited their interaction with the patients while with the second group, the practitioner “augmented the interaction,” by creating a warm, empathetic, and confident patient-practitioner relationship.”  Let’s call the patient-practitioner interaction as either ‘cold’ or ‘warm’.

The proportion of patients who reported adequate relief of IBS symptoms:  28% on the waiting list control group, 44% in the ‘cold’ or limited group sham acupuncture group, and 62% in augmented ‘warm’ group.¹²

Most naturopathic doctors pride themselves as being caring and empathetic, thus creating warm relationships with their patients.  If that is the case, we should expect that over 60% of our IBS patients will improve merely from placebo effect alone.  No matter what treatment you choose, nearly 2/3 should improve.   

In drug trials, placebo response rates are typically around 35%, about what Beecher reported in his 1955 clinical paper.¹³ The more invasive the treatment, the stronger the placebo effect. Half of the patients who receive placebo surgery to treat pain have subjective improvement in pain.¹⁴  Even little things make a difference in placebo effect.  The bigger the pill, or the more pills in a dose, the bigger the effect.  Even the color of the pill matters.  So do brand names compared to generics, and obviously more expensive placebos are more effective than cheaper ones. There are multiple ways to enhance placebo effect and as long as we are being honest and not deceptive, there is no reason not to enhance the potential for patient benefit.

This recurring percentage of patients who respond to placebo has been consistent over the years, enough so that when we see only about a third of patients respond to treatment we should be suspecting we are seeing placebo effect rather than treatment effect. 

In the seventy plus years since Beecher’s original “Powerful Placebo” paper was published, there have been detractors.  Gisela Kienle and Helmut Kiene have probably been the loudest of these detractors writing several papers published in the late 1990s attacking Beecher’s work.¹⁵ ¹⁶ ¹⁷ They “undertook to refute the entire concept of placebo response by critically examining the validity of Beecher’s paper. Although they claimed to have analyzed 800 publications, they focused on the same fifteen studies on which Beecher’s paper was based. They concluded that Beecher had “totally misinterpreted the trials and even accused him of misquotation in ten of the fifteen trials he had analyzed.”  They argued that a variety of unrelated phenomena might explain the improvement of symptoms seen.¹⁸  Kienle and Kiene apparently had a strong ulterior motive for wishing to discredit the existence of a placebo effect.  Their own research studies were directed toward proving the efficacy of anthroposophical medicine. Their arguments attempting to weaken the placebo concept provided an excuse for their own failure to show anthroposophical therapies were superior to placebo in randomized clinical trials.¹⁹ If placebo effect wasn’t real and could be discounted, then their clinical trials could be seen as effective.

Supporters of complementary and "alternative" medicine (CAM), such as Kienle and Kiene, are among the strongest critics of the placebo concept. They correctly point to conceptual problems in the way the term "placebo" is often used, the empirical shortcomings of some scientific studies of the placebo effect, and the fact that the term "placebo" is often used over inclusively, subsuming several other psychological phenomena that can make inert treatments appear valid. We attempt to clarify here some conceptual issues surrounding the placebo concept and review studies of placebo effects. This article argues that the real reason CAM supporters wish to denigrate the concept of the placebo is to justify CAM's failure to do controlled studies of their treatments that would show whether their methods were more than mere placebos. CAM supporters' attempts to tarnish the placebo effect are really an attempt to make scientific medicine look as weak as CAM. They argue that what critics dismiss in CAM treatments as mere placebo effects are actually real therapeutic effects. Rather than excusing CAM's failure to use randomized clinical trials (RCTs), however, arguments such as those of Kienle and Kiene support our contention that other confounds can make pseudoscientific treatments appear plausible.¹⁵ ¹⁶ ¹⁷ Well-controlled RCTs are more rather than less necessary when evaluating CAM therapies.

In the last fifteen years, much information has been garnered from research data on open-label placebos.  Multiple meta-analyses now summarize these studies.  An August 2025 meta-analysis by Johannes Fendel et al, which included 60 RCTs of open-label placebos, reports benefits in both clinical and non-clinical settings: but placebos were more effective in clinical settings. This would suggest that treatments performed or initiated in the office might be more effective than when started at home.  This would justify the traditional practice of having the patient take their first dose of a medication while still in your office.

Placebo effects were more pronounced when assessed through self-reporting rather than objective measurements.  The list of conditions upon which open-label -placebos have been shown effective now includes relieving  chronic pain, such as low back pain and migraine headaches, functional disorders such as IBS, allergic rhinitis, and other conditions that include addiction support, cancer-related fatigue and menopausal hot flashes.  All are to some degree subjective complaints and might be generalized as ailments of self-regulation or sensory regulation: situations in which some homeostatic mechanism is out of adjustment.  Pain is perceived as too intense, immune reactivity is too responsive, bowel transit time as too fast or too slow and so on.  

The effect of placebo treatments can be long-lasting.  Several studies on chronic back pain stand out in this regard: they suggest placebo response may persist over long periods of time.  Ashar reported in 2014 that a single saline placebo injection in a tender location of the back was associated with pain relief for the full year the patients were monitored.’  The patients not only felt less pain but also reported significant improvements in anxiety, depression and sleep during the full twelve months.²⁰   

Claudia Carvalho et al initially reported in 2016 that open-label placebo treatments were helpful for chronic low back pain.²¹ Five years later their research team followed up with these original patients and found that: “Improvements persisted after 5 years and were accompanied by substantial reductions compared with baseline in the use of pain medication (from 87% to 38%), comprising analgesics (from 80% to 31%), antidepressants (from 24% to 11%), and benzodiazepines (from 15% to 5%)”.²² The common assumption that placebo relief would be short-lived seems to be false.

Ted Kaptchuk is quoted as saying, "Placebos may make you feel better, but they will not cure you."¹  Yet, for someone whose life is restricted by chronic back pain or IBS or any of the other conditions that respond well to placebo, the chance to feel better for an extended period of time might still be a welcome relief. 

In naturopathic medicine, we speak about stimulating the Vis Medicatrix Naturae, that force that heals from within the body, and that our goal is to do so with the least effort or force possible.  If that is so, can we think of anything more naturopathic than the placebo effect?

References

1.  Kaptchuk TJ, Friedlander E, Kelley JM, et al.. Placebos without deception: a randomized controlled trial in irritable bowel syndrome. PLoS One. 2010 Dec 22;5(12):e15591.

2. BEECHER HK. The powerful placebo. J Am Med Assoc. 1955 Dec 24;159(17):1602-6.

3. Tracey, I. Rethinking placebos. Nat Med 20, 807 (2014). https://doi.org/10.1038/nm.3648

4. AMA Code of Ethics opinion 2.1.4. Use of Placebo in Clinical Practice.   https://code-medical-ethics.ama-assn.org/ethics-opinions/use-placebo-clinical-practice (accessed April 15, 2026.

5.  LIBERMAN R. An analysis of the placebo phenomenon. J Chronic Dis. 1962 Aug;15:761-83.

6.  PARK LC, COVI L. NONBLIND PLACEBO TRIAL: AN EXPLORATION OF NEUROTIC PATIENTS' RESPONSES TO PLACEBO WHEN ITS INERT CONTENT IS DISCLOSED. Arch Gen Psychiatry. 1965 Apr;12:36-45. PMID: 14258363.

7.  Ballou S, Kaptchuk TJ, Hirsch W, et al. Open-label versus double-blind placebo treatment in irritable bowel syndrome: study protocol for a randomized controlled trial. Trials. 2017;18(1):234.

8. Ballou S, Haas JW, Iturrino J, et al. Psychological Predictors of Response to Open-Label Versus Double-Blind Placebo in a Randomized Controlled Trial in Irritable Bowel Syndrome. Psychosom Med. 2022;84(6):738-746.

9.  Lembo A, Kelley JM, Nee J, et al. Open-label placebo vs double-blind placebo for irritable bowel syndrome: a randomized clinical trial. Pain. 2021;162(9):2428-2435.

10.  Wang RS, Lembo AJ, Kaptchuk TJ, et al. Genomic Effects Associated With Response to Placebo Treatment in a Randomized Trial of Irritable Bowel Syndrome. Front Pain Res (Lausanne). 2022;2:775386.

11.  Ford AC, Moayyedi P. Meta-analysis: factors affecting placebo response rate in the irritable bowel syndrome. Aliment Pharmacol Ther. 2010 Jul;32(2):144-58.

12.  Kaptchuk TJ, et al. Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome. BMJ. 2008 May 3;336(7651):999-1003

13.  Enck P, Klosterhalfen S, Weimer K, Horing B, Zipfel S. The placebo response in clinical trials: more questions than answers. Philos Trans R Soc Lond B Biol Sci. 2011 Jun 27;366(1572):1889-95.

14.  Gu AP, Gu CN, Ahmed AT, et al. Sham surgical procedures for pain intervention result in significant improvements in pain: systematic review and meta-analysis. J Clin Epidemiol. 2017 Mar;83:18-23.

15.  Kienle GS, Kiene H. Placebo effect and placebo concept: a critical methodological and conceptual analysis of reports on the magnitude of the placebo effect. Altern Ther Health Med. 1996 Nov;2(6):39-54.

16.  Kienle, Gunver S. and Helmut Kiene. “The powerful placebo effect: fact or fiction?” Journal of clinical epidemiology 50 12 (1997): 1311-8.

17.  Kienle, G. S. and Helmut Kiene. “The placebo effect: a scientific critique.” Complementary Therapies in Medicine 6 (1998): 14-24.

18. Scheindlin S. The problematic placebo. Mol Interv. 2009 Jun;9(3):108-13.

19.  Jittler, S. & Beyerstein, D.F. & Beyerstein, B.L.. (2003). Placebo effects: A conceptual analysis and a reply to Kienle and Kiene. Scientific Review of Alternative Medicine. 7. 41-60.  https://www.researchgate.net/publication/285987594_Placebo_effects_A_conceptual_analysis_and_a_reply_to_Kienle_and_Kiene

20.  Ashar et al. Open-Label Placebo Injection for Chronic Back Pain With Functional Neuroimaging: A Randomized Clinical Trial. JAMA Netw Open. 2024 Sep 3;7(9)

21.  Carvalho C, et al. Open-label placebo treatment in chronic low back pain: a randomized controlled trial. Pain. 2016 Dec;157(12):2766-2772. 

22.  Carvalho, C Pais, M; et al. Open-label placebo for chronic low back pain: a 5-year follow-up. PAIN 162(5):p 1521-1527, May 2021.