A new Israeli study shows that positive expectation can strengthen the immune response. In fact, this is the first direct evidence for the placebo effect on the human immune system.
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A 26-year-old man, generally healthy, was rushed to the emergency department of a large medical center in the United States after swallowing a blister pack of pills in a suicide attempt. Upon arrival, he was in critical condition: He was pale, sweating, and trembling, and suffered a life-threatening drop in blood pressure. He was therefore transferred to the intensive care unit, where he received aggressive fluid resuscitation to stabilize his blood pressure. During treatment, the young man managed to tell his physicians that he had swallowed a blister pack of an experimental drug that had been given to him as part of a clinical trial. Shortly thereafter, one of the study physicians arrived and clarified that the participant had actually been assigned to the placebo arm and had not received any active medication. Within about 15 minutes of hearing this, his condition improved dramatically—the tremor ceased, blood pressure and heart rate returned to normal values, and he appeared completely stable. He was later discharged home.
This documented medical case is an (extreme) example of the nocebo effect (from Latin: “I shall harm”)—the inverse of the better-known placebo effect (from Latin: “I shall please”) [1].
The placebo and nocebo effects illustrate the power of thought and the brain to influence the body in a medical context: Even without a direct pharmacological effect, simply believing that one is taking a drug can induce a bodily response similar to that of the drug itself—albeit usually weaker. In certain conditions—such as depression, anxiety, and chronic pain—symptoms are affected not only by measurable biological deficits but also by expectations, thoughts, and emotions. The placebo effect is an active brain-body response to information, expectation, and the therapeutic context, with the capacity to alleviate symptoms. Conversely, when the expectation is of harm or deterioration, the same mechanism can exacerbate symptoms, producing a nocebo effect. Various studies have shown that the placebo effect influences behavioral measures, the autonomic nervous system, and even the immune system [2].
But what biological mechanism can explain the placebo effect, or at least parts of it? Animal studies have shown that one brain region associated with expectation, reinforcement, and reward lies in the brainstem. This region, called the VTA (ventral tegmental area), is part of the mesolimbic system and includes neurons that release the neurotransmitter dopamine [3]. In animals, activation of neurons in the VTA and the mesolimbic system affects the immune system—for example, accelerating recovery from bacterial infections, cancer, and heart attacks [4]. There is also evidence indicating a connection between the VTA and immune activity in humans, but the precise mechanisms remain unclear.
An Israeli research group recently published the results of an innovative interventional study providing direct evidence that, in humans, the placebo effect influences immune activity and that brain activity linked to reward processing is associated with antibody production after vaccination. The findings were published in the journal Nature Medicine [5].
Healthy volunteers were recruited and divided into three groups. One group was instructed to focus on activating the mesolimbic reward network; a second group was instructed to activate other, non-mesolimbic networks; and the third group received no instructions to activate any particular neural network. To identify which brain areas were engaged, the researchers employed neurofeedback training combined with fMRI scanning—a technique that allows real-time monitoring of brain activity and feedback to the participant. The experiment was double-blinded: The participants did not know which network they were asked to activate, and the investigators did not know each participant’s group assignment.
Guided by the researchers, participants practiced various mental strategies—imagery, positive thoughts, or emotions—thereby learning how to activate the desired neural networks in their brains. After completing the training, all participants received a hepatitis B vaccine, and immune function was assessed through blood samples collected before vaccination and several weeks and months afterward.
The results showed that increased neural activity in the VTA was accompanied by higher antibody levels after vaccination, i.e., better immune protection. Activating other neural regions was not linked to a similar effect. The rise in VTA activity was chiefly associated with positive expectation, a central component of the placebo effect.
The findings indicate that the immune response in humans can be modulated via a brain mechanism mediated by positive expectation. The study demonstrates the power of thought to enhance immune function in contexts like medical treatment or vaccination and proves that expecting a positive outcome and believing in a treatment’s efficacy strengthen immune activity and can improve the body’s response to various medical interventions.
Of course, large-scale studies are still required to determine whether these findings have clear, practical medical benefits. In any case, there is reason behind the saying “Think positive, and positive things will happen”: at the very least, you might get more out of your annual flu shot.
Hebrew editing: Smadar Raban
English editing: Elee Shimshoni
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Daniel is a physician (M.D.) specializing in neurology at the Tel Aviv Medical Center, and he holds a PhD in the physiology and pharmacology of the nervous system from Tel Aviv University.
