People Need Both Drugs and Faith to Get Rid of Pain Researchers have discovered how the brain releases opioids in the placebo effect

Aug. 1, 2007  -- In one startling drug study in the 1980s, a young woman who had been virtually homebound by the energy-sapping effects of chronic fatigue syndrome had a miraculous recovery.

But, it wasn't the drug that cured the patient – she was in the trial group that was taking sugar pills. It was the "placebo effect," — a well-documented phenomenon that has intrigued doctors for decades.

When patients believe a drug will help them, they sometimes heal themselves.

"She and her parents were so excited about her profound improvement," said Janet Dale, a staff scientist at Clinical Investigation at the National Institute of Allergy and Infectious Diseases. "And she sustained her health and continued to be well."

It's human nature, explained the study scientists, who reported nearly 50 percent of the participants on placebos got better.

But now, with advances in neuroscience, researchers at Columbia University and the University of Michigan have been able to see how the placebo effect works.

When volunteers were convinced they were receiving pain medicine, their brains actually released natural relief, or opioids.

"It is the first time we have been able to directly observe placebo-induced pain relief," said neuroscientist Tor Wager of Columbia University, whose findings also showed that drug effectiveness is enhanced by the power of the mind.

"We usually think a drug does something to you, but there are examples in which the drug doesn't do anything unless we have the correct belief," he said. "You need both the chemical and faith that the drug will work."

"We're not there yet," said Wager, but this discovery could change the treatment of pain and disease.

One day doctors might be able to determine which patients are more responsive to placebos and use lower doses of powerful medicines that can cause side effects and allergies.

The study, which was published in Proceedings of the National Academy of Sciences, "is another piece of evidence that the person is not just changing the way you say you feel, but how it is processed in the brain," said Wager.

The word "placebo" is Latin for "I will please." Placebos like sugar pills, distilled water or saline solutions have been used for decades in drug research and by doctors.

In a 1955 ground-breaking paper, "The Powerful Placebo," researcher H.K. Beecher concluded that one-third of all patients responded to a placebo.

In later studies, when patients were told they were taking stimulants, their blood pressure and pulse rates rose; when they thought they were taking sleeping pills, they fell.

But the most significant research in placebos has been seen in the treatment of pain relief. In some studies up to 75 percent of patients responded to sugar pills, according to the Food and Drug Administration.

"Placebo groups are included in virtually every major clinical trial, which is a testament to their importance," said Wager. "Only in the past few years have scientists developed the tools to directly investigate how placebos work in the human brain."

Morphine Mimics the Brain

Doctors have used the chemical opiate morphine to treat pain for two centuries, so scientists like Wager have theorized that if morphine "mimics what the brain does naturally, the brain must have its own internal chemical."

In the placebo study, Wager and his colleagues tested 15 volunteers with two "pain relieving" creams — one had an active ingredient and the other was inert. The creams looked identical and both were applied on the forearm.

Researchers applied a thermode — or hot plate — against the skin, giving a sequence of painful stimuli, similar to a hot cup of coffee. Volunteers were asked to rate the pain.

During the experiment the volunteers' brain activity was monitored with positron emission tomography (PET). Scientists were looking for differences between reported pain and brain activity.

When the placebo cream was applied, volunteers were told "this is a proven pain-reliever," and that it would work, explained Wager. "We wanted to make sure to convince them so they really believed it blocked pain when they were stimulated on the placebo-treated skin site."

The PET scans revealed activity in both the frontal cortex – the area of the brain that controls conceptual knowledge, and in the periaqueductal gray area – the region that governs basic responses to threat and is involved in pain suppression.

Earlier placebo research used magnetic resonance imaging (MRI) to look at the brain, but PET scans now let these scientists look directly at the nerve chemistry of the brain and its opioides.

Drug companies have long known the power of placebos, according to Scientific American.

"It is why drug companies sue each other over the right to have a purple pill rather than a blue one?" a 2004 article asked. "Blue pills have the connotation of sadness and couldn't possibly, to the placebo-induced mind, make us better. It's called 'trade dress,' and the shape of the pill — the color, the size — accounts for the efficacy of a pill sometimes as much as what is in it."

In drug trials, scientists must inform volunteers when they are given placebos, but some ethicists worry that when used outside research, placebos can undermine the essential trust between patient and doctor.

Doctors Called 'Con Artists'

Some even go so far as to call doctors "con artists" for prescribing placebos for panic attacks, migraines and other complaints.

At Winthrop-University Hospital on New York's Long Island in 1999, an intern gave a patient complaining of pain a saline injection rather than an active drug. The hospital's ethics committee prompted a survey published in the Western Journal of Medicine that showed interns admitted ordering placebos for patients 10 times over two years.

"I have no issue with using placebos with patients as long as a physician indicates that this may be part of their practice so that a general consent to the use of placebo is obtained," said Dr. Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania.

Every patient needs to know the drugs they are taking if they change doctors or move, said Caplan. Physicians also need to keep careful records of placebo use.

"Sometimes talking to the patient and calming them down is a placebo," said Caplan. "Sometimes offering an aspirin can be a placebo. And many prescription drugs carry a placebo effect."

Joan McGregor, professor of philosophy and bioethics at Arizona State University, agrees that the mind can influence the body, citing the power of prayer, meditation and social groups.

"We waste a lot of money on drugs and invasive therapies when we could go in another direction," said McGregor. "We ought to be studying this and harnessing the power of the mind."

The placebo study is a start, according to Columbia's Wager, and it may eventually give scientists insight into why many drugs have a range of effects on people, how drugs and other treatments work together with psychological states, and how psychology can be effectively used in treatment.

"The human brain not like a machine, but like a river with a lot of ongoing processes," said Wager. "What you do when you give someone a drug is you nudge that and produce all sorts of ripple effects."