Zeebo® in Publications and Clinical Research

A Randomized, Double-Blind, Placebo-Controlled Pilot Trial With Open-Label Extension of Sirona, a Hydrogel for Weight Loss

Byrne J, et al. · NIHR Southampton Biomedical Research Centre, University Hospital Southampton, UK · Sponsor: Oxford Medical Products (OMP) · ISRCTN14083641

This double-blind, placebo-controlled pilot RCT (N = 40 adults, BMI 30–41) evaluated Sirona, a novel dual-polymer hydrogel pill for weight management. Zeebo supplied the matched placebo comparator. The study found the treatment was safe and well tolerated, with participants on Sirona showing greater weight loss compared to placebo. The trial was registered on ISRCTN (14083641) and results published in the peer-reviewed journal Obesity.

"The placebo pills (Zeebo Effect LLC) consisted of microcrystalline cellulose (96%), and they were the same size, color and shape and similar weight to Sirona pills."

— Obesity, Wiley / NIHR Southampton Biomedical Research Centre, 2024

Effects of Open-Label Placebo on Pain, Functional Disability, and Spine Mobility in Patients with Chronic Back Pain

Kleine-Borgmann J, Schmidt K, Hellmann A, Bingel U · University Hospital Essen, Germany · Registered: DRKS00012712

This RCT (N = 127 patients, chronic back pain duration >12 weeks) found that a 3-week open-label placebo treatment produced significantly greater reductions in pain intensity and patient-reported functional disability than TAU alone. Depression scores also improved. Summarized in American Family Physician (2021) with explicit reference to Zeebo as a nonprescription option for clinicians.

"Our study demonstrates that a 3-week open-label placebo treatment is safe, well tolerated and reduces pain, disability, and depressive symptoms in chronic back pain."

— PAIN, International Association for the Study of Pain, 2019

Non-Deceptive Placebos Reduce COVID-Related Stress, Anxiety, and Depression

Guevarra DA, et al. · Michigan State University / University of California, San Francisco

This RCT examined the effects of non-deceptive placebo on a population experiencing long-term stress during the COVID-19 pandemic. Compared to a no-treatment control group, the Zeebo OLP group showed significantly accelerated reductions in COVID-related stress, overall stress, anxiety, and depression over two weeks. The authors note the strong scalability potential of remotely administered OLP for populations without access to conventional mental health services.

"Remotely administered non-deceptive placebos have the potential to help individuals struggling with mental health concerns who otherwise would not have access to traditional mental health services."

— Applied Psychology: Health and Well-Being, IAAP, 2024

Open-Label Placebo Treatment for Cancer-Related Fatigue: A Randomized-Controlled Clinical Trial

Hoenemeyer TW, Kaptchuk TJ, Mehta TS, Fontaine KR · University of Alabama at Birmingham Comprehensive Cancer Center · NCT02522988

This IRB-approved RCT (N = 74 cancer survivors with moderate-to-severe fatigue) found that open-label placebo produced a 29% improvement in fatigue severity and a 39% improvement in fatigue-disrupted quality of life compared to treatment as usual, with medium-to-large effect sizes (d = 0.63 and d = 0.76 respectively). Among the first studies to establish OLP efficacy in an oncology population.

"Results demonstrate that even when administered openly, placebos improve cancer-related fatigue (CRF) in cancer survivors and dopaminergic systems may be associated with this response."

— Scientific Reports, University of Alabama at Birmingham, 2018

Effects of Open-Label Placebos on Test Performance and Psychological Well-Being in Healthy Medical Students

Kleine-Borgmann J, Schmidt K, Billinger M, Forkmann K, Wiech K, Bingel U · University Hospital Essen, Germany

This single-blinded RCT (N = 80 healthy medical students) demonstrated that a 21-day course of Zeebo open-label placebo significantly reduced subjective stress, fatigue, and confusion compared to controls during examination periods. Test performance was not improved overall, though within the OLP group, performance correlated positively with medication beliefs — indicating an expectation-modulated response.

"OLP can counteract negative effects of acute stress on psychological well-being and might improve cognitive performance if supported by positive treatment expectations."

— Scientific Reports, Nature Publishing Group, 2021

Open-Label Placebo Treatment Does Not Enhance Cognitive Abilities in Healthy Volunteers

Hartmann H, Forkmann K, Schmidt K, Kleine-Borgmann J, Albers J, Wiech K, Bingel U · University Hospital Essen, Germany / University of Oxford, UK

This pre-registered RCT (N = 78 healthy volunteers) investigated whether a 21-day Zeebo OLP treatment could enhance multiple sub-domains of cognitive performance. The study found no improvements in objective cognitive outcomes — including attention, working memory, and instrumental learning — while confirming the replicability of the Zeebo OLP protocol. An important null-result contribution to the open-label placebo literature.

"Our study thus highlights possible limitations of OLP treatment in boosting cognitive performance in healthy volunteers. These findings are discussed in the light of expectancy-value considerations that may determine OLP efficacy."

— Scientific Reports, Nature Publishing Group, 2023

Open-Label Placebo Treatment for Experimental Pain: A Randomized-Controlled Trial with Placebo Acupuncture and Placebo Pills

Lee S, Choi DH, Hong M, Lee IS, Chae Y · Kyung Hee University, Seoul, Republic of Korea

This randomized crossover trial (N = 34 healthy participants) compared three conditions — OLP pill (Zeebo), OLP acupuncture, and no treatment — for experimental heat pain. Both OLP interventions outperformed no treatment. OLP acupuncture produced greater analgesia than OLP pills, attributed to the richer ritual and sensory experience of acupuncture. The study directly supports the role of delivery context and ritual in shaping OLP response — a finding relevant to Zeebo's branded pill design philosophy.

"The authors found significant analgesic effects of the placebo pill and placebo acupuncture in the OLP condition."

— Journal of Integrative and Complementary Medicine, Kyung Hee University, 2022

No Long-Term Effects After a 3-Week Open-Label Placebo Treatment for Chronic Low Back Pain: A 3-Year Follow-Up

Schmidt K, et al. · University Hospital Essen, Germany

This longitudinal follow-up found no significant differences in pain intensity, disability, or mood between the original OLP and TAU groups at the 3-year mark. The short-term benefits observed in the parent RCT were not sustained. The study contributes important long-term safety and durability data and informs optimal dosing duration for future OLP trials.

"Given OLP's tolerability and safety, these findings indicate that they can have clinically relevant short-term benefits."

— PAIN, University Hospital Essen, 2023

From Catastrophizing to Catalyzing: Does Pain Catastrophizing Modulate the Beneficial Impact of Open-Label Placebos for Chronic Low Back Pain?

Caliskan EB, Schmidt K, Hellmann A, Spisák T, Bingel U, Kleine-Borgmann J · University Hospital Essen, Germany

This secondary analysis investigates whether pain catastrophizing — a maladaptive cognitive pattern characterized by rumination, magnification, and helplessness — moderates OLP response in the original Essen back pain cohort. Counterintuitively, the findings suggest that higher catastrophizing may predict better OLP response, pointing to the role of cognitive flexibility and expectation-modulation in placebo mechanisms. Implications for identifying optimal Zeebo users.

"These findings suggest that OLP treatment may provide measurable benefits for a specific subset of patients, supporting its potential as a personalized intervention in managing chronic back pain."

— Frontiers in Psychology, University Hospital Essen, 2025

The Association Between Test Anxiety, Learning Strategies, and Open-Label Placebo Effects on Academic Test Performance

University Hospital Essen team · Germany

This secondary analysis (N = 104) explores whether test anxiety and learning strategies predict OLP response in the original Essen exam stress cohort. Key finding: students with higher test anxiety who took Zeebo scored significantly better on their central examination than controls — a moderate effect size (d = 0.43). OLP intake also benefited students who used effective learning strategies. Supports targeted use of Zeebo for exam stress in anxious students.

"OLP intake compared to no intervention was associated with improved test performance in those students with higher levels of test anxiety and those who adopted beneficial learning strategies (LS)."

— Frontiers in Psychology, University Hospital Essen, 2025

Open Label Placebo to Reduce Prescription Opioid Use

Registered on ClinicalTrials.gov · United States

This registered trial investigates whether open-label placebo can reduce prescription opioid consumption, reflecting growing interest in non-pharmacological approaches to opioid stewardship. The Zeebo protocol is employed as the OLP intervention.

"These findings suggest that OLP treatment may provide measurable benefits for a specific subset of patients, supporting its potential as a personalized intervention in managing chronic back pain."

— Frontiers in Psychology, University Hospital Essen, 2025

Chronic Orofacial Pain: Genetics, Cognitive-Emotional Factors, and Endogenous Modulatory Systems — Phase II Open-Label Placebo Extension

Colloca L, MD PhD · University of Maryland School of Nursing · Study No. HP-00068315 · Sponsor: National Institute of Dental and Craniofacial Research (NIDCR), NIH

This NIH-funded Phase II open-label placebo extension study investigates whether Zeebo can extend the beneficial effects of placebo responses in patients with chronic orofacial pain. Led by Prof. Luana Colloca MD PhD — one of the world's leading placebo researchers and a steering committee member of the Society for Interdisciplinary Placebo Studies — at the University of Maryland School of Nursing. IRB-approved July 2022. Results pending publication.

Short-Term Low Back Pain Relief with Placebo

Shaughnessy AF · American Academy of Family Physicians

This POEM (Patient-Oriented Evidence that Matters) evidence review summarizes the Kleine-Borgmann 2019 RCT and assigns a Level of Evidence of 2b. The review concludes that patients with long-term low back pain who knowingly took placebo twice daily reported less pain and disability than those receiving treatment as usual, and specifically names Zeebo as a nonprescription option available to practitioners.

"A nonprescription placebo (Zeebo) is available, or pharmacists can prepare placebo capsules. (Level of Evidence = 2b)"

— American Family Physician, AAFP, 2021

Placebos in Clinical Care: A Suggestion Beyond the Evidence

Maher C, O'Keeffe M, Traeger A · University of Sydney / NHMRC

This peer-reviewed commentary in a major Australian medical journal evaluates the evidence base for open-label placebos in clinical care, explicitly referencing Zeebo as a commercially available product. Published in PMC/PubMed Central, the citation contributes to Zeebo's indexed academic presence internationally.

"...so-called open label placebos have moved beyond research settings and it is now possible to purchase Zeebo (Zeebo Effect) placebo pills branded as 'Zeebo Relief Pure Honest Placebo.'"

— Medical Journal of Australia, University of Sydney / NHMRC, 2021

The Placebo Cure: And Other Mind Body Effects

Uwe Heiss · ISBN 9781522021056 · Independently published

The Placebo Cure covers the scientific history of placebos and how understanding of the placebo effect has evolved — from a nuisance to be controlled in clinical trials to a therapeutic mechanism in its own right. Topics include: the neuroscience and biochemistry of placebo response; how expectation, conditioning, and ritual shape outcomes; the ethics of honest placebo; what makes a placebo experience more or less effective; and the emerging concept of third generation placebos — containing no active or potentially harmful substances, intentionally designed for effect, and taken with full awareness. The book argues for a paradigm shift in how medicine relates to patients, expanding the scope of care beyond conventional pharmacological intervention.

"Third generation placebos — the subject of Mr. Heiss' book — will likely be revolutionary. It is humbling to realize that our body and mind is quite plastic. Imagine if placebos received even a fraction of the advertising publicity that conventional drugs do. We'd all be regular consumers of placebos and much better off for it."

— Verified Amazon Review, United States, August 2018 · 5 stars

The Consumer Guide to Placebos: How to Choose a Placebo and Create Your Own Safe Path to Well-Being

Uwe Heiss · Zeebo Effect, LLC

A concise practical guide for anyone curious about using honest placebo safely. Introduces a common language for talking about placebos, describes what makes them work, and outlines simple rules for designing your own placebo experience. Written for the general public rather than researchers or clinicians — the accessible entry point to the ideas developed more fully in The Placebo Cure.

Can the Open Label Placebo Rationale Be Optimized?

Heiss U, Rosenfield M, Bernstein MH · Zeebo Effect, LLC / Brown University School of Public Health

This peer-reviewed perspective examines how the rationale provided to patients during OLP administration affects treatment outcomes, with a focus on pain and chronic conditions. It proposes an optimized framework for OLP rationale delivery — including the role of mindfulness and expectation-setting in modulating response magnitude.

Open-Label / Non-Deceptive Placebos: Experimental Design Practice

Macmillan Learning Psychology Blog · 2024 · United States

This teaching blog post on Macmillan Learning — one of the world's largest academic publishers, whose materials are used by hundreds of universities — uses the Guevarra 2024 Zeebo study as a worked example to teach undergraduate psychology students about open-label placebo experimental design. Zeebo is named and described in detail, including its labeling, instructions, and price point. The post also cites the finding that more expensive placebos are more effective — noting Zeebo's premium positioning in the market.

"Where does one get placebos, you ask? Amazon. For this study, researchers used Zeebo's blue and white capsules."

— Macmillan Learning Psychology Blog, 2024

A Burlington Entrepreneur Aims to Market a Placebo

Seven Days · April 1, 2015 · Vermont, USA

Vermont's leading independent news weekly covered Zeebo at launch, introducing the concept of honest placebo to a general audience and profiling Uwe Heiss as the founder bringing the product to market.

Even If Your Doctor Tells You That Pill Is A Placebo, It Might Still Make You Feel Better

Rita Rubin · Forbes · May 31, 2017 · USA

A science feature in Forbes covering the emerging field of open-label placebo research, naming Zeebo as an available honest placebo product and contextualizing it within the clinical evidence on OLP efficacy.

People Are Now Taking Placebo Pills to Treat Themselves

TIME · August 23, 2018 · USA

One of the highest-profile mainstream media features on the honest placebo movement, published in TIME magazine. The article profiles Zeebo founder Uwe Heiss — described as a "placebo activist and health care transformer" — alongside Dr. Jesse Hoover, a practitioner customer who began offering Zeebo to patients seeking alternatives after exhausting conventional options. Heiss describes his personal practice of taking Zeebo daily with a spoken intention — focusing the mind on a specific symptom or goal at the moment of taking the pill. The feature reaches TIME's global readership of millions.

Vertrouwen in placebo ("Trust in Placebo")

Ronald Veldhuizen, science journalist · Skepter, Issue 4, 2019 · Netherlands

A feature interview with the late Prof. Dr. Andrea Evers (Leiden University), one of the world's leading placebo researchers, awarded the Stevin Prize — the Netherlands' highest science honor — for her placebo research. The article explores placebo and nocebo effects in clinical practice and highlights Zeebo alongside her research as an example of honest placebo moving from research into commercial availability. Published in Skepter, the peer-adjacent Dutch science magazine of Stichting Skepsis, with a circulation of approximately 2,900.

The Promise of Pills that Do Nothing

Beryl Lieff Benderly · Proto.life · October 14, 2021 · USA

Proto.life, the science publication of Massachusetts General Hospital, covered the emerging honest placebo field with Zeebo as a central example — bringing the concept to a medically sophisticated readership of clinicians, researchers, and health professionals.

A New Alternative Medicine: 'Honest' Placebos

Ellen Phiddian · The Saturday Paper · October 2, 2021 · Australia

Australia's The Saturday Paper covered the honest placebo movement with Zeebo as a named product, reflecting the field's growing international reach. The article contextualizes OLP within the broader alternative medicine landscape and the clinical research supporting it.

Misleiding of niet? Webwinkel Amazon verkoopt placebopillen, maar helpen ze ook? ("Misleading or not? Amazon sells placebo pills — but do they work?")

VRT NWS · Belgian Public Broadcasting · September 2022 · Belgium

A science feature on VRT NWS — the Belgian public broadcaster — examining honest placebo pills sold on Amazon. Part of the broader Flemish public media coverage of the open-label placebo field in 2022, coinciding with increased European clinical interest in honest placebo as a clinical tool.

Got a Cold? A Placebo Might Help

Elie Dolgin · Science News · 2025 · USA

Science News covered emerging research on placebo effects for cold and respiratory symptoms, naming Zeebo Relief pills specifically as an available honest placebo option for consumers. A timely and practically oriented feature from one of the most respected science news publications in the United States.