Agreeable? You’re More Likely to Benefit From Placebo

The next time you take a pill to relieve a headache, time how long it takes until the pain disappears. If it’s less than 15 minutes, chances are good that you benefited more from a placebo effect than your ibuprofen. The placebo effect—feeling better without active medication—has long been known to account for many of the benefits we expect from drugs ranging from anti-depressants to migraine relief. But according to a study published in Neuropsychopharmacology this month, your personality determines how likely you are to experience it.

According to the study, agreeable and resilient people are more likely to have their pain soothed by a placebo. Neurotic people, on the other hand, are less likely to benefit. During a painful experience, agreeable and resilient people also showed more activity in a brain region presumed to suppress pain.

Jon-Kar Zubieta, a neuroscientist at the University of Michigan, has studied the brain mechanisms behind placebo effects for a number of years. He and researcher Marta Peciña examined the brain activity of fifty volunteers during a PET scan. Before the scan, volunteers were injected with a chemical, carfentanil, that binds to opioid receptors in the brain. Opioid receptors are the brain’s mediators of pain relief. For example, morphine numbs pain by binding to opioid receptors.

Volunteers experienced two conditions, pain and pain with placebo. During the PET scan, they had a needle placed in their jaw muscle, the masseter. To cause pain, the needle pumped highly salty water into the masseter. Previous studies have shown that this is painful—I hope I never have to find out from experience.

For the placebo, the volunteers were told that in addition to the painful saltwater in their jaw, they would receive an injection of a “pain relief medication…thought to have analgesic effects through the activation of natural brain systems that suppress pain.” The pain relief medication was actually just an injection of water that had the same amount of salt as body fluid, but contained no active drugs.
During both the pain and the placebo condition, the volunteers rated their pain on a scale of 0 to 100 every 15 seconds.

The volunteers reported significantly less pain when they thought they were receiving medication, even though it was just water. During the painful condition, volunteers rated their pain a 30 out of 100, but when they received a placebo they rated the pain a 24. The placebo was an effective pain reliever. This is not surprising, as numerous studies have shown that placebos can affect the way we feel.

They also had the volunteers fill out personality questionnaires looking at resilience, agreeableness, optimism, impulsivity and neuroticism. Volunteers’ experience of a placebo effect, it turned out, depended on their personality. The volunteers who scored highest on agreeableness and resilience were significantly more likely to feel relief from the water injection. On the other hand, highly neurotic volunteers were less likely to feel relief. None of the other personality traits impacted the placebo effect.

What’s more, when Peciña and Zubieta looked at brain activity, they found a relationship between agreeableness, resilience and analgesic effects in the brain. Volunteers who were more agreeable and resilient had less available opioid receptors in the dorsal anterior cingulate cortex. Less available opioid receptors suggests that the receptors are already occupied by endorphins—pain relievers produced within the brain. The dorsal anterior cingulate is known to be involved in both the experience of pain and the placebo effect, so it makes sense that endorphins that bind to opioid receptors in this region would cause pain relief.

It’s been shown before that personality can mitigate or enhance the placebo effect, but it was less clear how this was happening. This study suggests that personality affects the way our brains respond to medication. Resilient and agreeable people release more endorphins in the dorsal anterior cingulate than the average person when they believe they’ve taken medication.

Placebo Essential Reads

Placebo Effects and Direct-to-Consumer Advertising

Is Optimism the World's Most Powerful Placebo Effect?

Peciña and Zubieta suggest that agreeable people may have a stronger alliance with their doctor or treatment provider that compels them to desire better results. The tendency to want to please others seems to be related to release of endorphins in response to pain. It may be that the desire to feel better leads to release of endorphins that causes genuine relief.

Resiliency is the ability to recover from stressful situations, such as pain. This study suggests that part of the advantage that resilient people exhibit is greater release of endorphins during pain.

Neuroticism, on the other hand, meant that volunteers were less likely to experience a placebo effect and had less endorphin activity in the anterior cingulate cortex. Peciña and Zubieta suggest that aspects of neuroticism, specifically anger, have been linked to decreased function of the opioid system.

As someone who often wonders whether effects are due to substances, like caffeine in coffee, or placebo, this study also offers some suggestions. If an agreeable person discusses the benefits of a drug, I might not believe them. If a neurotic person praises a drug, I’ll feel confident the effect is real.

To read more about the placebo effect and the brain, see this recent post by Art Markman, Ph.D.