Withdrawal from Cigarette Smoking Is Associated With Changes in Brain Regions That Regulate Mood

by Dr Sam Girgis on August 2, 2011

Cigarette smoking cessation and the process of quitting tobacco use is extremely difficult.  More than half of cigarette smokers who quit will relapse during the first 2-3 days due to the symptoms of withdrawal.  Tobacco use is highly addictive and has been thought to be more addictive than alcohol, cocaine, methamphetamines, and even heroin.  There are very severe and well known detrimental health consequences caused by tobacco smoking, and they include but are not limited to emphysema, chronic bronchitis, respiratory infections, lung cancer, heart disease, and stroke.  The incentive to quit smoking is great for many smokers, but despite this many often fail and require multiple attempts before complete abstinence is achieved.  Researchers from the Centre for Addiction and Mental Health in Toronto, Canada lead by Dr. Ingrid Bacher have shown that changes occur in the brain during the tobacco withdrawal process that are involved in mood regulation.  The researchers have shown that the levels of monoamine oxidase A (MAO-A) are increased in the prefrontal cortex and the anterior cingulated cortex in heavy smokers during withdrawal.  The results of their study were published online in the journal Archives of General Psychiatry.  For their study, the researchers recruited 24 healthy nonsmokers and 24 otherwise healthy cigarette smoking individuals.  The study participants underwent positron emission tomography (PET) with harmine labeled with carbon 11.  The healthy participants underwent PET scans of their brains only once.  The cigarette smoking participants underwent PET scans of their brains after acute withdrawal from tobacco and after active cigarette smoking.   The cigarette smokers were classified as either heavy (over 25 cigarettes daily) or moderate (15-24 cigarettes daily).  The results showed that there was a significant increase in MAO-A binding during withdrawal in the heavy smoker group.  MAO-A was increased by 23.7% in the prefrontal cortex and by 33.3% in the anterior cingulated cortex in heavy smokers during withdrawal as compared to active smoking.  During withdrawal, MAO-A binding was greater in heavy smokers by 25.0% in the prefrontal cortex and by 25.6% in the anterior cingulated cortex compared to healthy controls.  The change in the MAO-A binding was correlated with the smokers reported level of depression.   The authors wrote, “ours is the first study, to our knowledge, of brain MAO-A binding during early cigarette withdrawal. To better explain the complexity of acute cigarette withdrawal after heavy smoking, we argue for adding a new model to previously established mechanisms, focusing on the rapid change in available MAO-A binding. During the withdrawal state in individuals who smoke heavily, MAO-A binding increases rapidly in affect modulating brain regions, such as the prefrontal cortex and anterior cingulate cortex, with MAO-A binding exceeding levels observed in healthy nonsmoking individuals. A greater increase in MAO-A VT in the prefrontal and anterior cingulate cortices may contribute to a shift toward depressed mood… The increase in MAO-A VT during acute withdrawal also argues in support of additional clinical trials of MAO-A inhibitors for the earliest stages of quitting heavy cigarette smoking, during which relapse rates are highest”.  This is an important study that provides insight into the biochemical changes that occur in the brain during the tobacco withdrawal process.  Using this knowledge, future studies can evaluate the possible role for MOA-A inhibitors in the treatment of tobacco withdrawal which could translate into improved success for those attempting a smoking cessation program.


Ingrid Bacher et al. “Monoamine Oxidase A Binding in the Prefrontal and Anterior Cingulate Cortices During Acute Withdrawal From Heavy Cigarette SmokingArch Gen Psychiatry. 2011;68(8):817-826. doi:10.1001/archgenpsychiatry.2011.82

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{ 4 comments… read them below or add one }

Mary August 3, 2011 at 7:45 am

Can you provide some insight on hooka smoking? Some argue its less addictive than cigarattes.


Dr Sam Girgis August 3, 2011 at 9:32 pm

Hooka tobacco smoking is equally as addictive as cigarettes. In addition, the smoke from a hooka may have more negative health consequences as it is unfiltered smoke despite being cooled by the water.


Charles W. Stills August 20, 2011 at 12:16 am

I have not smoked in a while, however i do indulge in a little bit of smokeless tobacco (Dip) from time to time whats your perspective Dr Sam? I also have one more question-are cigarettes more dangerous than marijuana?


Dr Sam Girgis August 20, 2011 at 7:11 pm

Smokeless tobacco (Dip) may not carry the same lung cancer risk, but there is an increased risk of oral and throat cancer associated with it’s use. Tobacco cigarettes and marijuana cigarettes are dangerous in different ways. Marijuana cigarettes likely have higher concentrations of toxins and carcinogens due to the unfiltered nature of the type of smoke. Marijuana cigarettes can be equated to smoking unfiltered hand rolled tobacco cigarettes. In addition, I believe that marijuana can serve as a “gateway” drug that can lead to the use of other addictive substances. Marijuana is illegal, except when prescribed by a physician in only a handful of states for the treatment of chemotherapy and HIV induced anorexia and nausea. I strongly suggest that you do not use any of these substances.


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