A study published in Nature Medicine identified a link between the placebo effect and immune system function. In the experiment, individuals who generated positive expectations showed a stronger immune response to vaccination against hepatitis B.

The research, conducted by researchers from Tel Aviv University, Tel Aviv, and the Technion, Haifa, Israel, demonstrated that voluntary activation of the brain’s reward system, particularly the ventral tegmental area (VTA), a key dopaminergic-producing center in the brain, was correlated with greater antibody production after a vaccine dose.

To test this hypothesis, 85 healthy participants underwent functional MRI (fMRI) monitoring. They were divided into three groups: an experimental group trained to activate the reward system with a focus on the VTA, an active control group trained to activate other brain regions unrelated to reward, and a control group that received no mental training.

Neurofeedback Training

The researchers used an fMRI-based neurofeedback technique. “It is a method in which participants learn to increase or decrease their own brain activity and voluntarily control it,” explained Nitzan Lubianiker, PhD, the study’s lead author and neuroscience researcher at the School of Psychological Sciences, Tel Aviv University.

During the sessions, participants observed their brain activity in real time on a screen. Volunteers in the experimental group were instructed to increase their VTA activity by engaging in positive thoughts about the future and cultivating optimistic expectations. They tested different mental strategies and could immediately identify which approaches were most effective through live monitoring.

Speaking with Medscape’s Portuguese edition, Lubianiker said, “What is interesting about this technique is that people receive feedback about what works, so they gradually learn which thoughts increase or decrease the signal in that brain region and then modulate it.”

“In a way, it provides access to a process that is usually unconscious. We are not aware of our brain activity, of what happens in specific brain regions, but in this way, we can learn to control them through mental strategies.”

After the imaging sessions, all participants received a dose of the hepatitis B vaccine. “We cannot know when the immune system will be exposed to an infection in order to generate antibodies, so vaccination was a way to test immune response,” said Talma Hendler, MD, PhD, the study’s principal investigator. “Hepatitis B was chosen because it is a very common vaccine that many people receive for travel or educational requirements,” she added.

Immune Effects

Several weeks later, blood samples were collected to measure antibody production in the participants. The goal was to determine whether the brain state induced immediately before vaccination influenced vaccine efficacy at the immune level.

The results showed a clear association between brain activity and immunity. Participants who successfully activated the VTA produced higher levels of antibodies against hepatitis B weeks after vaccination. Individual capacity to engage the reward system had a positive effect on immune response following vaccination.

“We demonstrated the responsiveness of the immune system [to stimulation of the reward system], but not healing, symptom relief, or changes in disease behavior in the body. Those aspects still need to be studied,” Hendler cautioned.

Rather than transient states of happiness or pleasure, it was the deliberate act of building hopeful, future-oriented expectations that allowed the brain activity required to stimulate immune function. According to the authors, the findings suggest that hope is not merely an abstract feeling but a trigger capable of activating concrete biological defense mechanisms.

“If someone suffers an injury, needs surgery, and feels hopeful about the outcome, believing it will help and that recovery is possible, they are more likely to improve and recover. This has been studied and is known as the placebo effect,” said Lubianiker. “People who believe they can get better do, in some cases, improve, but the neurobiologic mechanism mediating this effect has never been very clear.”

The findings provide a neurobiologic basis for the placebo effect, suggesting that expectations of recovery activate dopaminergic pathways that, in turn, signal the immune system to respond more robustly.

Clinical Implications

“What we showed is that the mental state of the patient receiving a vaccine, the environment in which the dose is given, and the physician’s receptiveness can all affect immune response,” Lubianiker said.

The researchers emphasized that all participants who received the vaccine were immunized against hepatitis B and that the study does not challenge the effectiveness of vaccination protocols. Rather, the placebo effect may act as an immune system “accelerator.” In the experiment, participants would not have developed antibodies without the vaccine.

In clinical practice, these findings may encourage a more positive professional approach and the creation of a clinical environment that conveys safety and trust. “It is important to understand patients’ fears and try to alleviate them as much as possible, without deception and without giving false hope, but by showing the potential for recovery,” Hendler suggested.

The study indicates that physicians are not only technical prescribers but also agents who can modulate treatment efficacy through communication. Creating an environment of realistic optimism, discussing the chances of recovery or improvement, and encouraging a positive patient mindset may function as a biological adjunct that enhances responses to conventional treatments, according to the researchers.

“It is an easy and relatively low-cost way to influence patient improvement,” Hendler said.

Positive thinking and an optimistic attitude do not replace evidence-based medicine, the authors stressed. Physicians should continue to provide accurate and correct information, but within a framework that promotes hope.

“It is the physician’s responsibility to provide patients with an accurate prognosis; however, our study indicates that the context in which the treatment is delivered matters. If the environment is positive and the physician gives the patient a reason to hope, that is a good thing,” Lubianiker concluded.

Letícia Naísa is a Brazilian science journalist with a degree from PUC-SP in São Paulo, Brazil, a specialization in science journalism from Labjor/Unicamp, and a master’s student in science and cultural communication at the same institution.

This story was translated from Medscape’s Portuguese edition.