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Chronic drinking and smoking cause both separate and interactive brain injury

January 25, 2006

Most alcoholics in North America are chronic smokers. While much is known about the adverse effects of chronic smoking on cardiac, pulmonary and vascular function as well as the risk for various cancers, little is known about its effects on brain neurobiology and function. Symposium participants at the June 2005 annual meeting of the Research Society on Alcoholism in Santa Barbara, California addressed the brain injuries that chronic smoking and drinking can cause separately as well as interactively. Proceedings are published in the February issue of Alcoholism: Clinical & Experimental Research.

"Recent neuroimaging studies of chronic smokers have shown brain structural and blood-flow abnormalities," said Dieter J. Meyerhoff, professor of radiology at the University of California, San Francisco, associate researcher at the Veterans' Affairs Medical Center San Francisco, and symposium organizer. "Specific cognitive dysfunction among active chronic smokers has been reported for auditory-verbal learning and memory, prospective memory, working memory, executive functions, visual search speeds, psychomotor speed and cognitive flexibility, general intellectual abilities, and balance. We also believe that the adverse effects of smoking, just like drinking, likely take many years to impact brain function significantly, and interact with age to produce a level of dysfunction that is apparent on cognitive tests."

Symposium key proceedings included:

- Genetic factors and pharmacological interactions between alcohol and nicotine may be critical determining factors in the very common co-occurrence of chronic drinking and smoking.

"Any behavioral manifestation, including alcoholism or addiction to nicotine, is a result of genetic-environment interactions," said co-author Yousef Tizabi. "Drugs, including alcohol and nicotine, may affect different individuals differently, depending on their genetic make-up. Similarly, drug-drug interactions are also influenced by genetic factors. Therefore, co-morbidity of drinking and smoking can be considered to be a final outcome of genetics, environment, and pharmacological interactions between alcohol and nicotine."

- Smoking may attenuate gamma-aminobutyric acid (GABA)A receptor adaptations associated with alcohol dependence and may contribute to the co-occurrence of alcoholism and smoking. In light of this, benzodiazepines used to treat alcohol withdrawal may have different effects on alcohol-dependent individuals who smoke versus those who do not.

"GABA is an inhibitory amino acid in the human brain and is critical in counterbalancing the biological action of the excitatory amino acid glutamate," explained Meyerhoff. "In a healthy human brain, both amino acids are present in equilibrium. In disease stages such as addiction, to either alcohol or nicotine, this equilibrium is out of balance. During alcohol withdrawal, GABA concentrations may increase, but the densities of receptors are still relatively low. Benzodiazepines may strengthen the responses of (GABA)A receptors to GABA binding, thereby having a soothing effect on the user."

- In-vivo magnetic resonance studies suggest that chronic smoking in recently detoxified alcohol-dependent individuals compounds alcohol-induced brain tissue loss and neuronal injury. Chronic smoking may also hinder neurobiological and cognitive recovery during short-term abstinence from alcohol.

"We studied recently detoxified alcoholics in treatment using in-vivo magnetic resonance," said Meyerhoff. "The specific methods we used were magnetic resonance imaging (MRI), which measures the size of many different brain structures, and magnetic resonance spectroscopic imaging (MRSI), which measures certain naturally occurring chemicals in the brain that tell us about injury to specific brain cells. Our analyses showed that chronically smoking alcoholics have greater brain abnormalities - that is, less brain tissue measured by structural MRI, and more neuronal injury measured by MRSI - at the beginning of their treatment for alcoholism than non-smoking alcoholics. And both groups had more brain abnormalities than non-smoking light drinkers."

Researchers also examined the recovery of regional brain metabolite concentrations in alcoholics who had been abstinent from alcohol for roughly one month. "We found significant increases of two important brain metabolite markers of cell viability in the frontal and parietal lobes of recovering alcoholics," said co-author Timothy Durazzo. "For most brain regions, these increases were apparent in non-smoking recovering alcoholics, not smoking recovering alcoholics, which suggests that chronic cigarette smoking may adversely affect metabolite recovery. The process by which chronic cigarette smoking affects brain metabolite recovery has yet to be established. It is possible that continued smoking in recovering alcoholics during short-term abstinence imparts a major [and] sustained direct source of harmful free radical species and, in combination with carbon monoxide exposure and possibly reduced brain perfusion, may hinder brain tissue recovery in smoking recovering alcoholics."

- Both chronic smoking and drinking have an impact on cognitive function: for measures of fast, flexible performance, smoking may explain the effect formerly attributed to chronic drinking; for other measures such as IQ or response inhibition, both chronic smoking and drinking may predict neurocognitive function.

"Our quantitative MRI results suggest chronic alcoholism and smoking both are associated with cortical gray matter loss," said Meyerhoff. "This leads to atrophy, which in general is a risk factor for greater-than-normal global cognitive decline and memory impairment in the elderly and, if occurring in middle age, may increase the risk for earlier and more rapid cognitive decline in old age. Therefore, smoking alcoholics, particularly those who are in their late 40's or older, may place themselves at even greater risk for abnormal cognitive function with advancing age."

Meyerhoff said that, collectively speaking, the research discussed during the symposium may help raise awareness that chronic smoking itself has detrimental effects on the brain and its function. "These effects are similar to effects that in the past have been attributed solely to the excessive consumption of alcohol," he said. "As chronic alcohol drinking and chronic smoking more often than not co-occur, researchers have begun to realize that the brain effects previously attributed to alcohol drinking alone may in fact be the result of both drinking and smoking. This realization may have consequences for how we look at treatment for alcohol-use disorders."

University of California, San Francisco School of Medicine