Ethanol, Ethyl Alcohol, Spirits, all of them names for the simple molecule CH3CH2OH. It would be difficult to conceive of a string of letters that have had a greater impact on our global culture. From semi-clandestine high school parties, to ubiquitous college drinking, and even to such lofty heights as matrimony, the Eucharist, and other religious ceremonies, nearly every rite of passage is imprinted by alcohol’s distinctive hydroxyl signature. It is through these social means that we tend to romanticize and abstract alcohol. However, the biochemical reality is that the human body produces 3 grams of ethanol a day through normal fermentation processes alone and that this catabolic process is so essential to life that certain amino acid sequences in ethanol oxidation enzymes are conserved from humans to bacteria. No matter how ornate the chalice, nor how benign the plastic cup, the chemical breakdown of alcohol in the body, and how it affects the brain, is immutably scientific and thus largely predictable. It provides a common framework for humanity, and an equalizing factor, which extends from the social to the biological realm. However, many of the most crucial truths about alcohol are shrouded in mystery due to social taboo. Questions regarding what alcohol does to our bodies both in the short and long term, and perhaps the darker sides of why we drink go largely unanswered. Hopefully this article will provide some answers to a college that, for better or worse, has what is undoubtedly a noticeably above-average love affair with the organic molecule alcohol.
What Happens when We Drink?
The complicated process incurred by ethanol consumption transforms the initial alcohol molecule first into acetaldehyde, then acetic acid, and finally to acetyl-CoA, at which point it enters the citric acid cycle (1). The final step is catalyzed by a complicated enzymatic synthetase reaction (1). The second step, however, is where most of the potentially adverse effects of alcohol occur. Acetic acid is an unstable compound, which is capable of forming toxic free radical structures if not supplied with sufficient antioxidants such as Vitamin C and Vitamin B1 (1). These radicals can cause a wide variety of ill-effects including birth defects in expecting mothers, severe liver and kidney damage in chronic alcohol abusers, and even the common hangover (1).
The first topic to consider is how we rate our own inebriation, which is generally measured in Blood Alcohol Content, or BAC. Although somewhat helpful in determining a subjective state of drunkenness, evidence suggests that this provides a misleading statistic in terms of how much alcohol is actually entering and subsequently affecting our bodies. This misconception is related to the first-pass effect, which is a drug phenomenon in which concentration of a given drug is dramatically reduced via drainage into the liver before it reaches systemic circulation. This effect has been shown in rats to cause a large discrepancy between ethanol ingested and both BAC and ethanol expelled from the blood (2). This implies that one’s level of intoxication is potentially dangerously unrelated to overall alcohol consumption and subsequent damage from its metabolism.
Another area of consideration in terms of alcohol’s physical properties is the neurological source and scope of alcohol’s psychoactive effects. Research indicates that alcohol stimulates the release of dopamine and serotonin in the nucleus accumbens, which is a collection of neurons within a subcortical region of the forebrain (3). Studies indicate that 1g/kg of alcohol is enough to significantly increase extracellular levels of these two neurotransmitters in rats (3). This finding may explain many of alcohol’s subjective effects. For instance, low levels of dopamine have been tied to social anxiety, which may explain the generally sociable effect alcohol inspires in people. However, psychological research indicates that this neurological change can result in what is known as “alcohol myopia” (4). This mental state is typified by a polarization of social and emotional responses, an enhancement of self-evaluation, and a temporary relief of anxiety (4). This perhaps helps to answer the age-old question of the subjective effect of alcohol on the psyche. It is not that alcohol is allowing an individual to intrinsically change, but rather to lower natural inhibitions. Thus, it is up to the individual to decide what role these inhibitions play in defining the self.
This alcohol myopia is not merely mental, but also physical and expresses itself in a gradient of physical impairment as alcohol consumption increases. Research indicates a significant linear correlation between subjects’ BAC and performance on a variety of cognitive psychomotor tests (5). Results suggested that for each 0.01% increase in blood alcohol, performance decreased by 1.16% (5). What this implies is that at a BAC of 0.10%, which is roughly the legal limit, performance drops by almost 12% (5). The other consideration of this research project was the effect of sleep deprivation on performance. For instance, after 17 hours awake, cognitive psychomotor performance was equivalent to that observed in individuals with a BAC around 0.05% (5). What this implies for the typical Dartmouth student drinking on a school day is that the roughly equal effects of sleep deprivation will compound any impairment from alcohol. The final consideration in terms of alcohol’s direct effects on students is the potential for injury. Not only are the above-described physiological effects likely to increase one’s chances for injury, but alcohol also has a potentially negative effect on cellular immunity, which is critical in defense of infection from acute injury. Research indicates that changes to cellular immunity are correlated to alterations in the cytokine milieu, which are found more prevalently in injury cases related to alcohol (6).
Why Do We Drink?
As previously mentioned, dopamine and serotonin are found to be released in higher levels upon consumption of alcohol. This basic evidence was used to try to explain alcohol-seeking behaviors in a neurobiological context. It was found that rats genetically selected to crave alcohol were also deficient in both serotonin and dopamine in regions of the nucleus accumbens (7). Similarly, any neurologically active agents targeted at increasing levels of serotonin or dopamine were able to assuage alcohol-seeking abilities (7).
What these results imply is that the lack of serotonin and dopamine (or neuronal receptors to receive them) in certain individuals may account for increased alcohol seeking behavior. Not only are these two neurotransmitters sought for the subjective effects that they directly incite (anxiety relief, euphoria, pain relief, etc.), but also because they are both involved in the brain’s reward pathway. Research has shown that dopaminergic neurons fire more when reward is perceived as imminent (1,7). In addition, when reward is greater than expected these neurons strengthen their firing in the future, which further solidifies this cycle of pleasure-seeking behavior (1,7).
Another trait of alcohol seeking rats was a greater basal level of anxiety (8). This is predictable, as lower levels of dopamine have been previously mentioned as leading to higher anxiety. Alcohol’s depressant effect on the CNS, which is mediated through its agonistic effect on GABA, is likely the explanation for more anxious rats seeking alcohol. GABA, which is the main mammalian inhibitory neurotransmitter, is increased in efficacy in the presence of alcohol. This leads to short-term relaxation, which more anxious rats, and perhaps people as well, would be incentivized to pursue.
The overarching theme to this string of research is that alcohol-seeking behavior likely has a large neurochemical component. This implies that each individual’s approach to alcohol is much more custom-tailored than originally thought. This goes beyond questions of tolerance in terms of weight or gender, and stretches into the very fabric of our individual brains, which are potentially each crafted on a spectrum of alcohol-seeking behavior.
Why Do We Abuse Alcohol?
Once again, rat models were used to genetically select for alcohol-seeking behavior. This time, the ventral tegmental area (9), which are a group of neurons located close to the midline on the floor of the midbrain, was looked at in detail during chronic alcohol consumption by rats. It was found that the projections of the VTA are potentially implicated in the reinforcing effects of drug abuse (9). The VTA in general has been found to be important in a variety of drug dependence and other psychological disorders (9). Again, dopamine plays the major role because the VTA is the origin of the dopaminergic cell bodies of the mesocorticolimbic dopamine system, which is largely involved in the aforementioned reward circuitry (9). Unfortunately, this system is essential for not only negative psychological processes such as addiction, but also motivation in general. The VTA is also connected to the aforementioned nucleus accumbens, which receives increased dopamine and serotonin activity in the presence of alcohol. Thus, compulsive drug abuse behavior is largely the result of modifications to both the VTA and the nucleus accumbens, which furnish their neurons with a greater ability to produce dopamine, and a greater sensitivity to dopamine (9). Because this cycle is both started, and propagated by dopamine itself, it is extremely difficult to break this cycle of addiction. It is also indicated by research that the neurobiological substrates in the VTA, which aid in the reward pathways of alcohol are likely influenced by genetics (9, 10). In addition, studies have explained that the withdrawal state during detoxification from alcohol is a physiochemical reality caused by the body entering a distress cycle due to its inability to restore homeostasis in the absence of the drug. Finally, any subsequent exposure after withdrawal symptoms have passed will re-instate the drug behavior. The neurological structure of the brain is permanently altered by chronic alcohol abuse.
There is hope, however, in the form of opioid (related to dopamine) antagonists such as naltrexone, which has been found to be helpful in the treatment of alcoholism (11). It seems that this drug, which decreases the amount of dopamine released by the brain, is capable of not only quelling the intense cravings felt by recovering alcoholics, but also of decreasing the euphoria experienced upon consumption of alcohol (11,12). There is also the potential to use the malfunctioning serotonin system, which is similarly implicated in alcoholism, to be both a source of preventative medicine, and a method of custom-tailoring alcohol recovery strategies to each patient (13). Pharmacological and clinical studies have shown that the 5-HT transporter and 5-HT1A are both candidates for loci of alcohol dependence (13). What this means is that detection of the malfunctioning serotonin allele could provide multiple therapeutic options.
What all of this evidence implies is that no matter how we view alcohol in the context of society or culture, it is still a drug with biochemical implications. Again, I am not advocating for or against the consumption of alcohol. The social inertia would make either argument ineffectual and largely pointless. I am rather hoping to provide a wide range of facts to put the effects of alcohol in a scientific, and thus predictable context. The bottom-line is that regardless of the nuances of weight, or age, or gender, ethyl alcohol will be metabolized by the body, and that will have an effect. The liver and kidneys will be shouldered with the responsibility of processing an influx of alcohol, and then aldehydes, and then acids. The nucleus accumbens and VTA will communicate in the language of neurotransmitters, and some individuals will be much more receptive to the neural restructuring that this will entail. This increased sensitivity can lead to alcoholism, but there is hope in the form of new drugs and therapies. It is important that we as Dartmouth students understand these facts instead of blindly consuming alcohol as though we were all uniformly equipped to deal with its effects. It is my prediction that until the day comes when social anxiety at every level has been extinguished, alcohol will continue to prevail as the recreational drug of choice. Until that potentially unreachable goal is achieved, it is important to understand what is possibly the most influential substance of all time.
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