Placebo. The word conjures up images of sugar pills and patients suffering from suspicious symptoms.

But after 16 months of a global pandemic, researchers are delving into the role of placebos in improving clinical trials, minimizing vaccine hesitancy, and treating so-called Long COVID-19. The role of placebos — anything that seems to be a “real” medical treatment but instead is a “fake” treatment that does not contain an active substance meant to affect health — has researchers exploring whether the power of the mind holds the key to changing the course of a person’s physical illness or pain when it comes to COVID-19, substance and alcohol use disorders, and more.

Nearly 500 researchers from 24 countries joined an online conference to discuss these topics, as well as the impact of placebos on pain management and addiction, during the 3rd International Conference for the Society for Interdisciplinary Placebo Studies (SIPS), hosted virtually by the University of Maryland, Baltimore (UMB).

“The past year living with the pandemic has highlighted our interconnectedness,” UMB President Bruce E. Jarrell, MD, FACS, said as he welcomed virtual attendees. “COVID-19 has shown the importance of strong relationships across disciplines and geographies to address major issues.”

Jarrell said he was proud of the interprofessional and multidisciplinary relationships and approaches that UMB professionals take to address health issues, including pain management and addiction.

“We hope to guide the next generations of health professionals and faculty to look across disciplines and to each other as possible solution finders, especially when addressing major health issues,” he said. “I hope that this conference provides a space for collaborative sharing of innovative research and ideas about placebo studies, engages you, and inspires you to learn and study more about how to integrate knowledge about placebo research in pain, alcohol use disorders, and substance use disorders.”

The three-day event offered a global platform for sharing ideas on how researchers see placebos being harnessed for good. Simply put, the placebo effect occurs when a placebo actually makes you feel better or improves your symptoms. The nocebo effect, on the other hand, happens when a placebo makes you feel worse.

Expert faculty from the UMB schools of Medicine, Nursing, and Pharmacy and UMB’s Institute for Clinical and Translational Research collaborated with SIPS to design the conference to advance the science of placebo research and mind-body mechanisms and to apply this knowledge to alcohol use and pain disorders. SIPS is an international association of scholars who share the goal of understanding the placebo effect in medical treatment, psychotherapy, and complementary and alternative treatments.

Joining Jarrell in welcoming attendees were E. Albert Reece, MD, PhD, MBA, executive vice president of medical affairs, UMB, and dean, University of Maryland School of Medicine (UMSOM); Natalie D. Eddington, PhD, FAAPS, FCP, dean, University of Maryland School of Pharmacy (UMSOP); Jane M. Kirschling, PhD, RN, FAAN, the Bill and Joanne Conway Dean of the University of Maryland School of Nursing (UMSON); and John Kelley, PhD, president of SIPS.

SIPS was founded in June 2014 at the Brocher Foundation, a Swiss conference center on the shores of Lake Geneva. Researchers from around the world were attending a conference to discuss psychotherapy and the placebo effect. During an outdoor after-dinner wine reception one evening, the idea for the society arose among a group of 12 conference attendees, including Luana Colloca, MD, PhD, MS, professor, Department of Pain and Translational Symptom Science, UMSON, and adjunct professor, Department of Anesthesiology, UMSOM, who would become a founding member.

For several years, Colloca and UMB collaborators have studied the role of placebo mechanisms for optimal pain management and treatment of alcohol and drug use disorders. She and other researchers believe placebo effects are a way to reduce health care’s reliance on addictive opioids and that the brain’s own power may be a solution to the opioid crisis. In 2018, she offered a TEDx talk at UMB on the topic “Are Placebos the Solution? Tackling the Opioid Epidemic in the Decades Ahead.”

“Although the acronym for our society refers to the interdisciplinary approach to the study of placebo effects, my recollection is the inspiration for the acronym, SIPS, had at least as much to do with the effect of the wine as it had to do with the placebo effect,” Kelley joked.

SIPS conferences were held in 2017 and 2019 in the Netherlands, at which time Colloca was asked to form a steering committee to bring a conference to Baltimore in 2021. Colloca reached out to colleagues in the schools of pharmacy, nursing, and medicine to see whether such an international meeting could be planned and hosted. The group also started applying for federal and nonfederal grants and were able to secure an R13 grant from the National Institutes of Health (NIH) that finances high-level scientific conferences compatible with NIH’s mission. Due to the pandemic, the Baltimore conference became a virtual event.

The event was sponsored by the National Institute on Alcohol Abuse and Alcoholism, the Samueli Foundation, and the German Research Foundation (DFG CRC/Transregio 289), according to Colloca.

“We wanted a conference to focus on translational aspects of placebo research and how the most recent findings can be applied to pain, alcoholism, and medicine in general,” Colloca said in an interview after the conference.

Jarrell thanked fellow conference steering committee members, including Colloca; Patricia Franklin, PhD, RN, adjunct assistant professor, UMSON; Jason Noel, PharmD, associate professor, UMSOP; and Chamindi Seneviratne, MD, assistant professor, UMSOM, each of whom presented on various topics during the conference, joining two keynote speakers and several other plenary speakers.

Colloca shared her recent research on immersive virtual reality, an innovative, off-the-shelf technology that aims to modify patients’ health care experience and expectations, leading to a possible positive effect on treatment outcomes. 

“The goal is to try to understand how virtual reality works. Is this a placebo, another mechanism of endogenous pain modulation?” she said. “And it is fascinating to see how this line of research is evolving in the lab from laboratory experiments to clinical trials, which shows the power of translational approaches. Is this virtual reality acting primarily on a distraction and attention mode? Or does some other mechanism of pain modulation become relevant? And if so, how can we exploit this mechanism to optimize virtual reality as an urgent therapeutic for patients?”

In another workshop, Colloca joined Seneviratne and Susan G. Dorsey, PhD, RN, FAAN, professor and chair, Department of Pain and Translational Symptom Science, UMSON, who also holds adjunct professor appointments at UMSOM and UMSOD, in discussing placebo responsiveness in pain and alcohol use disorders.

“Getting drunk on a glass of water. Perhaps this is an exaggeration, perhaps not,” Seneviratne said, showing a cartoon of a character at a bar displaying characteristics of drunkenness after drinking a glass of water. “This cartoon reminds me of a happy hour session we had some time ago to choose a placebo, the placebo beverage that mimics the effects of regular alcohol in a study that I’m going to be presenting to you today. I can still remember the perplexed look on my friend’s face when she realized that she was almost getting drunk on a glass of placebo beverage or the nonalcoholic beer.”

Such responses are not uncommon, Seneviratne said. “Placebo beverages have been shown to induce both biological or physiological responses as well as behavioral responses similar to alcohol beverages.”

Meanwhile, placebo and nocebo effects in the era of COVID-19 was an often-explored conference topic.

“Let me talk first about the misattribution of side effects following vaccines and vaccine hesitancy. I think this is really a true nocebo effect,” Arthur Barsky, MD, professor of psychiatry, Harvard Medical School, said while discussing “COVID-19: Society, Science, and Health Care in Year Two of the Pandemic,” along with Leonard Calabrese, DO, professor of medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland; Claire M. Fraser, PhD, professor and director, Institute for Genome Sciences, UMSOM; and Andrew L. Geers, PhD, professor of psychology, University of Toledo (Ohio).

“That is, some people following vaccination are manifesting symptoms that are not actually a physiological response to the vaccine itself, but are more attributable to anxiety, a misinterpretation and misunderstanding of the symptoms, and a misattribution to the vaccine,” Barsky added.

It is a well-known phenomenon that within minutes to hours after vaccination a number of people experience fainting, dizziness, shortness of breath, tachycardia, nausea, and vomiting. And these symptoms spread rapidly through a group of people who are in close contact with each other, such as in a choir or summer camp. Concerns, misgivings, misinformation, and anxiety about vaccination can cause people to notice unrelated symptoms and then amplify those symptoms and misunderstand their significance. Negative publicity about side effects of the vaccine, frightening messages in social media, alarming interpersonal communications, and hearsay about side effects foster hesitancy and deter people from getting vaccinated.

The issue of chronic symptoms following demonstrated infection of COVID-19 also raises questions for researchers. People with long-haul COVID-19 report a range of symptoms that also are prevalent in healthy populations unaffected by COVID-19.

“So, it’s a nocebo effect, in the sense that the symptoms that they are complaining about, and are attributing to COVID, actually are not due to the disease itself, but are due to a variety of other medical and psychosocial factors,” Barsky said.

Wayne Jonas, MD, executive director, Samueli Integrated Health Programs, another speaker and author of the book How Healing Works: Get Well and Stay Well Using Your Hidden Power to Heal, described placebo research as a sleeping giant in modern medical research that has yet to awaken.

“But when it does, it will play no favorites. It will be equally devastating to ancient healing claims, complementary medicine, and mainstream health care. I call that the placebo response,” Jonas said. “Why did I say it would be devastating? Because, in fact, it reveals what a lot of medical science currently conceals that is useful in healing.”

Wrapping up the first day of lectures, Jonas said placebo research has come a long way. “I think placebo has come of age now. The sleeping giant is beginning to wake, and it is largely because of the research that you have done,” Jonas told conference participants.

For more conference information and to view presentations, visit https://sips-conference.com/home.