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27 October 2004
Smoking Works Like Heroin On Brain 
Smokers say that lighting up calms their nerves, satisfies their cravings and helps them relax. Scientists from the University of Michigan think they now know why that might be - smoking produces major changes in the flow of "feel good" chemicals in the brain, both temporarily and long-term. 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 other opiate drugs. The new results - presented at the annual meeting of the Society for Neuroscience - 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 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. "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. "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. "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." 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. In the area of the brain called the anterior cingulate, which is involved in emotion and emotion-memory integration, the activity of the opioid system increased by about 20 percent. This meant that far more endorphins and enkephalins were being released during smoking. But the reverse was true in other key parts of the brain involved in memory, emotion and pleasure: the amygdala, the thalamus and the nucleus accumbens. In all three areas, the opioid system was 20 to 30 percent less active after the nicotine from the cigarettes was introduced. This sharp drop in activity, most significantly in the amygdala and the thalamus, correlated with simultaneous reports from the smokers about how they were feeling after they smoked the normal cigarettes. As the opioid activity in their amygdala and thalamus decreased, they reported feeling more relaxed, less alert and nervous, and less craving than before. Since smoking stimulates the release of dopamine in some of the same areas of the brain, Zubieta and his colleagues speculate that the connection between the opioid system and the dopamine system may be an important one to study. In the future, the team will be analyzing brain scans, self-reported ratings and genetic samples from more smokers and non-smokers, to give them a better picture of the interaction between nicotine, the opioid system, behavior and inherited traits.
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