Zeebo Effect, LLC  ·  Huntington, Vermont, USA

Zeebo® Placebo Pills in Published Clinical Research

Zeebo placebo pills and tablets have been reviewed by Institutional Review Boards (IRBs) and used as the investigational agent in published clinical research since 2014. Studies naming Zeebo have appeared in PAIN, Scientific Reports (Nature), American Family Physician, Frontiers in Pain Research, Obesity, and Applied Psychology: Health and Well-Being, among others.

All Zeebo research supply is produced at FDA-registered manufacturing sites in the USA following cGMP, with Certificate of Analysis and annual stability testing included.

8 Published Studies Naming Zeebo
30+ Institutional Research Customers
2014 First IRB Review
10+ Years Supplying Research

The 8 published studies below name Zeebo in their methods sections — drawn from a broader portfolio of engagements with more than 30 institutional research customers across the USA, Europe, and beyond since 2014. This page also includes field studies, peer-reviewed commentary, and co-authored works that are part of the broader open-label placebo research landscape in which Zeebo plays a central role.

Open-Label Placebo RCTs — Zeebo Supplied

Scientific Reports · Nature RCT · Zeebo Supplied 2021

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

Zeebo pills (Zeebo Effect, LLC, South Burlington, VT) were supplied as the open-label placebo agent. Participants took two capsules per day for 21 days during midterm examinations.

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
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PAIN · IASP RCT · Zeebo Supplied 2019

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

Zeebo placebo tablets were supplied as the investigational agent. Patients in the OLP group took Zeebo twice daily for 21 days in addition to treatment as usual (TAU).

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
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Applied Psychology: Health & Well-Being · IAAP RCT · Zeebo Supplied 2024

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

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

Zeebo blue-and-white capsules, purchased directly through Zeebo Effect, were mailed to participants and taken twice daily for two weeks. The study was administered remotely via Zoom — demonstrating scalability of Zeebo in decentralized trial formats.

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 would not have access to traditional mental health services."

— Applied Psychology: Health and Well-Being, IAAP, 2024
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Scientific Reports · Nature RCT · Zeebo Supplied 2023

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

Zeebo Relief pills (Zeebo Effect, LLC) were supplied in original packaging. Participants took one tablet twice daily for 21 days, replicating the established Zeebo OLP protocol from prior studies.

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.

"OLPs may enhance many aspects of functioning, but may not always work in all populations or against all symptoms — highlighting the importance of continued rigorous investigation."

— Scientific Reports, Nature Publishing Group, 2023
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Scientific Reports · Nature RCT · Zeebo Supplied 2018

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

Zeebo placebo pills were supplied as the investigational agent. Participants in the OLP group took two pills twice daily for 21 days.

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 — and dopaminergic systems may be associated with this response."

— Scientific Reports, University of Alabama at Birmingham, 2018
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Conventional Blinded RCT — Zeebo Supplied

Obesity · Wiley RCT · Zeebo Supplied 2024

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

Zeebo Effect LLC supplied custom placebo pills for this double-blind RCT. The paper states: "The placebo pills (Zeebo Effect LLC) consisted of microcrystalline cellulose (96%), and they were the same size, color and shape and similar weight" as the active treatment.

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 the 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."

— Obesity, Wiley / NIHR Southampton Biomedical Research Centre, 2024
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Follow-Up & Longitudinal Studies

PAIN · IASP 3-Year Follow-Up · Zeebo Supplied 2023

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

Follow-up of the 2019 Essen RCT (see above), which used Zeebo tablets as the investigational agent. Records from 89 of the original 122 participants were analyzed.

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, findings indicate clinically relevant short-term benefits — and underscore the need for studies examining longer treatment durations."

— PAIN, University Hospital Essen, 2023
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Registered Clinical Trials

ClinicalTrials.gov Registered Trial · Zeebo Supplied NCT05014230

Open Label Placebo to Reduce Prescription Opioid Use

Registered on ClinicalTrials.gov  ·  United States

Zeebo open-label placebo is the designated investigational agent for this registered trial.

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.

"A growing body of evidence demonstrates that no deception is necessary for placebo treatment to alleviate symptoms — including in opioid use disorder."

— ClinicalTrials.gov, NCT05014230, United States
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Foundational Field Research

PAIN · IASP Foundational Study 2016

Open-Label Placebo Treatment in Chronic Low Back Pain: A Randomized Controlled Trial

Carvalho C, Caetano JM, Cunha L, Rebouta P, Kaptchuk TJ, Kirsch I  ·  Beth Israel Deaconess Medical Center / Harvard Medical School / University of Lisbon

Placebo pills for this study were supplied by Bial (Porto, Portugal). This landmark Harvard/Beth Israel study is included here as the foundational RCT that directly catalyzed the subsequent Zeebo-supplied research at University Hospital Essen, University of Alabama at Birmingham, and elsewhere.

This landmark RCT (N = 83 completers) is among the most widely cited studies in the open-label placebo literature. OLP produced significantly greater pain reduction across all three numeric rating scales compared to TAU alone (composite: 1.5 vs. 0.2 on a 10-point scale), with large-effect improvements in functional disability. The study established OLP as a clinically meaningful intervention for chronic low back pain and is the direct predecessor of the Zeebo-supplied Essen studies.

"Our findings suggest that OLP pills presented in a positive context may be helpful in chronic low back pain."

— PAIN, Harvard Medical School / Beth Israel Deaconess Medical Center, 2016
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Published Works by Zeebo Effect

Frontiers in Pain Research Opinion / Perspective 2021

Can the Open Label Placebo Rationale Be Optimized?

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

Co-authored by Uwe Heiss, founder and CEO of Zeebo Effect, LLC, alongside researchers from Brown University's Center for Alcohol and Addiction Studies. Published as a peer-reviewed opinion and perspective article.

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.

"Mindfulness-based approaches to OLP delivery may enhance treatment outcomes by increasing present-moment awareness of placebo-associated sensations and expectations."

— Frontiers in Pain Research, Zeebo Effect LLC / Brown University, 2021
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Peer-Reviewed Commentary & Citations

American Family Physician · AAFP Clinical Evidence Review 2021

Short-Term Low Back Pain Relief with Placebo

Shaughnessy AF  ·  American Academy of Family Physicians

Zeebo is explicitly named as a commercially available nonprescription placebo option for clinicians — one of the first times a branded OLP product was recommended within a major clinical practice publication.

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
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Medical Journal of Australia · Wiley Peer-Reviewed Commentary 2021

Placebos in Clinical Care: A Suggestion Beyond the Evidence

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

Zeebo Relief (Zeebo Effect) is cited by name as an example of open-label placebos moving beyond research settings into clinical and consumer markets.

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.

"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
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Scientific Reports · Nature Methods Reference 2021

Open-Label Placebo Treatment to Improve Relaxation Training Effects in Healthy Psychology Students

Schienle A, Unger I  ·  University of Graz, Austria

The paper cites Zeebo-branded capsules as the OLP comparator standard from the Kleine-Borgmann 2021 study, establishing Zeebo as the reference product for the 21-day two-capsule-per-day OLP protocol used across multiple European trials.

This RCT (N = 160 psychology students) investigated whether OLP could improve compliance and outcomes in progressive muscle relaxation training. The study references the Zeebo protocol as the established methodological benchmark for open-label placebo pill research, reinforcing Zeebo's position as the field's standard research supply.

"The 21-day OLP application (two capsules per day labeled 'Zeebo') improved well-being — establishing it as the reference protocol for open-label placebo pill research."

— Scientific Reports, University of Graz, Austria, 2021
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Zeebo placebo pills and tablets contain Microcrystalline Cellulose (MCC), an inert fiber. Zeebo is produced at FDA-registered manufacturing sites in the United States following cGMP. Zeebo is not intended to diagnose, treat, cure, or prevent any disease. These statements have not been evaluated by the Food and Drug Administration. Research citations are provided for informational purposes; Zeebo Effect does not claim that its products replicate the outcomes of the studies listed above.

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Zeebo Research has supplied clinical trials since 2015. We provide custom and standard placebo capsules and tablets, a Certificate of Analysis, IRB Letter of Support, and ongoing stability test updates for multi-year studies.

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