When alcohol consumption is stopped too abruptly, the persons nervous system experiences uncontrolled synapse firing. This can result in symptoms that include anxiety, life-threatening seizures, delirium tremens, hallucinations, shakes and possible heart failure. Other neurotransmitter systems are also involved, especially dopamine, NMDA and glutamate.Severe acute withdrawal symptoms such as delirium tremens and seizures rarely occur after 1-week post cessation of alcohol. The acute withdrawal phase can be defined as lasting between one and three weeks. In the period of 3–6 weeks following cessation, anxiety, depression, fatigue, and sleep disturbance are common. Similar post-acute withdrawal symptoms have also been observed in animal models of alcohol dependence and withdrawal.A kindling effect also occurs in people with alcohol use disorders whereby each subsequent withdrawal syndrome is more severe than the previous withdrawal episode; this is due to neuroadaptations which occur as a result of periods of abstinence followed by re-exposure to alcohol. Individuals who have had multiple withdrawal episodes are more likely to develop seizures and experience more severe anxiety during withdrawal from alcohol than alcohol-dependent individuals without a history of past alcohol withdrawal episodes. The kindling effect leads to persistent functional changes in brain neural circuits as well as to gene expression. Kindling also results in the intensification of psychological symptoms of alcohol withdrawal. There are decision tools and questionnaires that help guide physicians in evaluating alcohol withdrawal.
These genetic factors influence the rate at which alcohol and its initial metabolic product, acetaldehyde, are metabolized. They are found at different frequencies in people from different parts of the world. The alcohol dehydrogenase allele ADH1B*2 causes a more rapid metabolism of alcohol to acetaldehyde, and reduces risk for alcoholism; it is most common in individuals from East Asia and the Middle East. The alcohol dehydrogenase allele ADH1B*3 also causes a more rapid metabolism of alcohol. The allele ADH1B*3 is only found in some individuals of African descent and certain Native American tribes. African Americans and Native Americans with this allele have a reduced risk of developing alcoholism. Native Americans, however, have a significantly higher rate of alcoholism than average; risk factors such as cultural environmental effects (e.g. trauma) have been proposed to explain the higher rates. The aldehyde dehydrogenase allele ALDH2*2 greatly reduces the rate at which acetaldehyde, the initial product of alcohol metabolism, is removed by conversion to acetate; it greatly reduces the risk for alcoholism.A genome-wide association study (GWAS) of more than 100,000 human individuals identified variants of the gene KLB, which encodes the transmembrane protein β-Klotho, as highly associated with alcohol consumption. The protein β-Klotho is an essential element in cell surface receptors for hormones involved in modulation of appetites for simple sugars and alcohol. Several large GWAS have found differences in the genetics of alcohol consumption and alcohol dependence, although the two are to some degree related.