Brain Chemicals Explain the Power of Placebos
How chemicals made in our brains reduce pain
By PATRICIA CHURCHLAND
Aug. 5, 2015 11:28 a.m. ET
We all know the basics of the placebo effect: Someone takes a sugar capsule that a trusted doctor has extolled as a breakthrough in pain relief, and the patient reports that the pain has disappeared. The logic would seem obvious: Either the patient never really had significant pain, or he still has pain but plays it down to please his doctor.
The seemingly obvious, however, is sometimes dead wrong. Researchers know that when someone expects a therapeutic benefit, the anticipation itself can have a real physiological effect on how much pain he feels, as well as on his emotions and cognitive performance.
But how can mere expectations change the brain’s response to pain? Over the past decade, research in many labs has revealed the central role played in this process by opioids and cannabinoids—chemicals routinely produced by our own brains. This evolutionary development goes back at least 450 million years to bony fish.
Structurally, these homegrown opioids resemble the opium derived from poppies, and homegrown cannabinoids resemble marijuana-derived cannabis. Both have docking sites on specific nerve cells, fitting as a key would into a lock. Through these receptors, the molecules change how a nerve cell behaves and hence how we feel.
Humans and other animals can get “high” from opium and its derivatives only because brains are normally wired with receptors for brain-generated opioids. If it weren’t for our cannabinoid receptors, smoking pot would be like smoking oregano. Counterbalancing the advantages of our brain-generated opioids and cannabinoids is the grim fact that our receptors allow for addiction to external sources, such as heroin and cannabis.
The opioids and cannabinoids we make act very similarly to morphine when it comes to dulling pain transmitted by pain-sensitive neurons. Imaging studies show that when a person’s pain ebbs, the pattern of brain changes is much the same whether it happens in response to a genuine analgesic such as morphine or to a placebo treatment. In both cases, multiple brain networks are affected, including structures known to regulate stress, fear, learning based on rewards and how we experience pain.
Placebos trigger the release of these chemicals under two conditions. One involves a social situation, such as reassurances from an admired or trusted physician. A subject expects a beneficial effect because of his deep-seated beliefs, his feelings and social attitudes. Just nibbling on snap beans with the hope of reducing joint pain is unlikely to do the trick.
Alternatively, a patient whose pain is diminished by morphine may, after repeated morphine injections, respond equally well to a placebo injection. This is called experience-dependent learning. In this case, the brain’s reward system has learned to expect pain reduction following an injection, and that expectation drives down the brain activities that sustain pain. Rats and dogs likewise have been found to display a placebo response that depends on such associations.
We still don’t understand well, however, the precise mechanisms that produce an uptick in homegrown opioid and cannabinoid action in anticipation of a therapeutic benefit. And not everyone responds to placebos.
Why not? In a 2013 paper in the journal Neuropsychoparmacology, Marta Peciña and Jon-Kar Zubieta at the University of Michigan and colleagues showed that people who have demonstrated physiological and psychological resilience in the face of stress, disease and injury also tend to respond well to placebos. A follow-up study by the researchers pointed to genetic factors. About half the population carries a genetic variant that results in more cannabinoids lingering in the body. But genes probably only partly explain the heightened effect of placebos.
So, yes, a patient’s placebo response is entirely in his head: He has a brain wired to exploit its own chemical helpers when it creates them in eager anticipation of relief.