Smokers often say that lighting up a cigarette can calm their nerves, satisfy their craving and help them relax.
Now, a team of University of Michigan scientists is reporting new evidence of why that might be: Smoking produces major changes in the flow of "feel good" chemicals between brain cells, both temporarily and long-term. And those changes in flow match up with changes in how smokers say they feel before and after smoking.
It's the first time smoking has been shown to affect the human brain's natural system of chemicals called endogenous opioids, which are known to play a role in quelling painful sensations, heightening positive emotions, and creating a sense of reward. It's the same system that is stimulated by heroin and morphine.
The research team, from the U-M Medical School, will present the results Tuesday afternoon in a lecture at the annual meeting of the Society for Neuroscience.
The new results come from a pilot study involving a small group of young male pack-a-day smokers and non-smoking comparison subjects. Despite their study's small size, the researchers say the surprisingly large effect on opioid levels they found suggests a promising road for further discovery. That may lead to better understanding of why smoking affects people the way it does -- including the mystery of why it's often so hard to quit, despite tobacco's many health dangers.
"It appears that smokers have an altered opioid flow all the time, when compared with non-smokers, and that smoking a cigarette further alters that flow by 20 to 30 percent in regions of the brain important to emotions and craving," says David J. Scott, a graduate student in the U-M Neuroscience Program who will present the results. "This change in flow as seen on a brain scan correlated with changes in how the smokers themselves reported feeling before and after smoking."
Scott and his colleagues made the findings using a type of brain scanning called positron emission tomography, or PET, imaging. This allowed them to literally see activity in the endogenous opioid system when the study participants first smoked a special cigarette with almost no nicotine, and then smoked a regular cigarette. Before, during and after the scans, the participants rated how relaxed, alert, sick and nervous they felt, and how much they were craving tobacco.
The new findings confirm previous animal studies, and add to scientists' previous understanding of how smoking affects the flow of another "feel good" chemical in the brain, called dopamine. Now, the team is studying the interaction of dopamine and opioids in the brains of smokers and non-smokers.
They also hope to look at underlying genetic differences that might explain variations between people in response to nicotine -- and perhaps differences in how easily people become addicted to cigarettes or quit smoking.
"The interaction of tobacco, and especially nicotine, with brain chemistry is a fascinating area that we're just beginning to understand, especially when it comes to correlating neurochemistry with behavior," says study leader Jon-Kar Zubieta, M.D., Ph.D., a U-M psychiatrist and neuroscientist. "Just as with the 'hard' drugs of abuse, such as heroin and cocaine, the phenomena of pleasure, addiction, increased tolerance and craving from tobacco are firmly rooted in neurochemistry."
Adds veteran tobacco researcher and U-M emeritus pharmacology professor Ed Domino, Ph.D., "Nicotine addiction is one of the most destructive forces in human health, and we must increase our comprehension of it in order to defeat it. This study represents a key step toward that goal."
Zubieta's team has spent several years developing and testing a way of using PET imaging to study the endogenous opioid system, and specifically the chemicals called endorphins and enkephalins.
Those are the same chemicals involved in the "runner's high", a pleasurable sensation brought on by strenuous exercise. But they're also important to blocking the flow of painful signals in the brain, and the U-M team has used the PET method to study how opioid levels change in response to pain, and how that response is affected by variations in hormone levels and genetic makeup.
The U-M team's PET scan method doesn't show the flow of opioids directly, but rather the status of tiny receptors on the surface of brain cells. These receptors, called mu-opioid receptors, act like locks that can only be opened when opioid molecules -- either made by the brain or introduced from outside -- bind to them. Morphine, heroin and some anesthetics produce their respective effects by binding to these receptors, and the drug-overdose treatment called Narcan blocks them.
The lower the level of natural opioids around, the more receptors there are available to other opioids -- such as a special molecule developed by the U-M team. It's made of a short-lived radioactive carbon atom attached to a molecule of carfentanil, a morphine-like drug known to bind only to mu-opioid receptors. Using the PET scanner, the team can detect how much carfentanil is binding, and by extension how much natural opioid is flowing in that area.
In order to study the effect of nicotine on the opioid system, the team had to find a way to perform their study in the U-M PET scanner despite the strict no-smoking policy of the U-M's Hospitals and Health Centers. They also had to simulate every aspect of smoking except the nicotine, in order to control for all the other chemicals in tobacco smoke and sensory aspects of cigarette smoking.