People say you need to think more positively as you get older to stay healthy. In fact, a study found that the same vaccine is more effective for positive people. Imagining positive experiences leads to more antibodies that detect and neutralize outside invaders.
A team led by Talma Hendler, a professor of psychiatry at Tel Aviv University in Israel, said on the 20th in the international journal Nature Medicine that "we confirmed that training to activate brain regions consolidation with reward and positive expectation increases the body's immune response to vaccines."
◇Placebo confirmed in hepatitis B vaccine
It is known that psychological state affects drug efficacy. The so-called placebo effect is a phenomenon in which taking a sugar pill or receiving a saline injection still brings therapeutic benefit because of the belief that it is a real drug. Conversely, when a real drug is prescribed but its effect diminishes due to the patient's negative thoughts, it is called the reverse placebo or nocebo effect.
The researchers tested whether the placebo effect also appears with vaccines in 85 people. The team administered training to boost positive thinking and then gave a hepatitis B vaccine. They drew blood at two and four weeks and analyzed antibodies.
In the experiment, people whose reward centers increased activity—making them feel pleasure and satisfaction—had higher antibody levels. The researchers said, "These results demonstrate that simply thinking positively can help strengthen the immune system," calling it "a placebo effect."
Before vaccination, the researchers had participants undergo psychological training to induce positive thoughts. The participants recalled enjoyable events, such as trips. During this, activity in the ventral tegmental area (VTA), the brain's reward center, was imaged with functional MRI (fMRI). When a specific region in the brain activates, blood flows to it. fMRI shows that region as if a light has turned on.
In the 1980s, it was revealed that when nerve cells in the VTA are activated, the neurotransmitter dopamine is released. This brings a reward that feels like pleasure and satisfaction. Participants were evaluated on their level of positive thinking based on fMRI images and repeated four training sessions to raise it. They identified which thoughts made the brain's reward center respond more strongly and focused training in that direction. The researchers said people who learned how to sustain reward-center activity showed a larger increase in antibody levels.
◇Negative thinking triggers COVID side effects
Conversely, it has already been confirmed that people with more negative thoughts get less effect from the same drug. A team led by Ted Kaptchuk at Harvard Medical School said in 2022 in JAMA Network Open that more than two-thirds of common side effects such as headaches or fatigue experienced by people who received vaccines for the novel coronavirus infection (COVID-19) appear to be due to the reverse placebo effect.
The researchers confirmed that among 45,380 people who reported side effects in 12 U.S. COVID vaccine clinical trials were those who received not only vaccines but also placebo injections. Clinical trials randomly assign participants to receive a real drug or a placebo to evaluate efficacy. Because it was not disclosed who received the real vaccine, side effects reported by vaccinated people can be seen as occurring at similar rates due to the reverse placebo effect.
Analysis showed that 76% of systemic side effects after the first vaccine dose, such as headaches or fatigue, were due to the reverse placebo effect. For the second dose, the reverse placebo effect accounted for 52% of side effects. Kaptchuk said in the paper, "Providing information about the placebo effect could reduce negative thoughts about vaccines and increase uptake."
At the time, the findings analyzed past clinical trial results and did not newly test to confirm the placebo effect. In this respect, the Israeli team's new results are meaningful because they newly tested to examine the placebo effect. Hendler said, "This appears to be the first human empirical study showing a causal relationship in which learning to leverage the brain's reward system increases the effectiveness of vaccination."
Of course, these results do not mean that disease can be treated by thought alone. However, the researchers said there is a possibility that psychological strategies could help the immune system fight infection and even suppress tumors. Larger clinical trials are needed to determine whether positive thinking has clear medical benefits. The team said they are investigating whether other parts of the immune system responsible for inflammatory responses are also influenced by psychological state.
References
Nature Medicine (2026), DOI: https://doi.org/10.1038/s41591-025-04140-5
JAMA Network Open (2022), DOI: https://doi.org/10.1001/jamanetworkopen.2021.43955