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What you don鈥檛 know won鈥檛 hurt you, goes the old canard, but what you believe can make a difference when it comes to pain relief, and not just in a subjective way. When you expect that a drug or placebo will relieve pain, and it does, it鈥檚 not simply a matter of fooling your brain.

That鈥檚 one lesson from intriguing new research co-authored by Associate Professor of Psychology and Neuroscience Tor Wager, director of CU Boulder鈥檚 Cognitive and Affective Neuroscience Lab.

鈥淎 placebo can cause you to believe something and that can have very deep effects on the emotional brain. 鈥� We are being fooled, led to have positive expectations, but that generates positive effects not just in the subjective sense but in how our brain functions,鈥� Wager says of 鈥淒issociable Influences of Opiates and Expectations of Pain,鈥� published in the June issue of The Journal of Neuroscience.

In two studies, Wager and his research partners from New York University, Columbia University and the University of Wisconsin, Madison examined the relationship between placebo and an opioid analgesic in physiological brain responses while manipulating the expectations of test subjects.

鈥淭o account for psychological factors, clinical trials assume that placebo effects are independent of drug effects and can be 鈥榮ubtracted away to reveal the true drug effect,鈥欌�� the authors write.

But, Wager says, the studies suggest that may not be the case, and that placebo-drug interactions 鈥� including expectations of relief 鈥� might work on different neurobiological processes and therefore have 鈥渁dditive鈥� effects.

鈥淚n fact, (opioids and placebos) affect different things in your brain when you use them side by side,鈥� he says. 鈥淭here is something about what we believe in treatment that isn鈥檛 simply duplicated by the drug effect.鈥�

The work has implications for the way clinical drug trials are conducted. He offers the example of a patient who is so drugged by the administration of opioids that she 鈥渄oes not have the cognitive machinery to generate expectations.鈥� In that case, you wouldn鈥檛 see an additive benefit of the placebo.

Wager describes beliefs or expectations as a way of anticipating future events, to which both brain and body respond.

鈥淚f you just won the lottery and Ed McMahon came to your house with the check, you haven鈥檛 got the money yet. But your entire body responds to the anticipation of having the money,鈥� he says. The same can be true of any expectation. 鈥淲e tend to think of beliefs as inconsequential, but the brain evolved to respond to them profoundly.鈥�

Does that mean any and all beliefs cause actual physiological responses in the brain? Not necessarily, Wager says. Many people, he says, capitalize on the placebo effect, such as those who perform 鈥渆nergy work.鈥�

鈥淯nless we can find plausible physiological mechanisms, I think we鈥檒l find a lot of (the response to these techniques) might be due to expectation,鈥� he says.

See a profile of Tor Wager in The New York Times听. See Tor Wager鈥檚 thoughts paired with those of other leading experts in Now Toronto听.