Chronic use of<unk>  leads to changes in brain chemistry especially in the GABAergic system. Various adaptations occur such as changes in gene expression and down regulation of GABAA receptors. During acute<unk>  withdrawal, changes also occur such as upregulation of alpha4 containing GABAA receptors and downregulation of alpha1 and alpha3 containing GABAA receptors. Neurochemical changes occurring during<unk>  withdrawal can be minimized with drugs which are used for acute detoxification. With abstinence from<unk>  and cross-tolerant drugs these changes in neurochemistry may gradually return towards normal. Adaptations to the NMDA system also occur as a result of repeated<unk>  intoxication and are involved in the hyper-excitability of the central nervous system during the<unk> . Homocysteine levels, which are elevated during chronic drinking, increase even further during the withdrawal state, and may result in excitotoxicity. Alterations in ECG (in particular an increase in QT interval) and EEG abnormalities (including abnormal quantified EEG) may occur during early withdrawal. Dysfunction of the hypothalamic–pituitary–adrenal axis and increased release of corticotropin-releasing hormone occur during both acute as well as protracted abstinence from<unk>  and contribute to both acute and protracted withdrawal symptoms. Anhedonia/dysphoria symptoms, which can persist as part of a protracted withdrawal, may be due to dopamine underactivity. Kindling Kindling is a phenomenon where repeated<unk>  detoxifications leads to an increased severity of the withdrawal syndrome. For example, binge drinkers may initially experience no withdrawal symptoms, but with each period of<unk>  use followed by cessation, their withdrawal symptoms intensify in severity and may eventually result in full-blown delirium tremens with convulsive seizures. People with<unk>  use disorder who experience seizures during detoxification are more likely to have had previous episodes of<unk>  detoxification than patients who did not have seizures during withdrawal. In addition, people with previous withdrawal syndromes are more likely to have more medically complicated<unk>  withdrawal symptoms. Kindling can cause complications and may increase the risk of relapse,<unk> -related brain damage and cognitive deficits. Chronic<unk>  misuse and kindling via multiple<unk>  withdrawals may lead to permanent alterations in the GABAA receptors. The mechanism behind kindling is sensitization of some neuronal systems and desensitization of other neuronal systems which leads to increasingly gross neurochemical imbalances. This in turn leads to more profound withdrawal symptoms including anxiety, convulsions and neurotoxicity. Binge drinking is associated with increased impulsivity, impairments in spatial working memory and impaired emotional learning. These adverse effects are believed to be due to the neurotoxic effects of repeated withdrawal from<unk>  on aberrant neuronal plasticity and cortical damage. Repeated periods of acute intoxication followed by acute detoxification has profound effects on the brain and is associated with an increased risk of seizures as well as cognitive deficits. The effects on the brain are similar to those seen in people who consume excess<unk>  who have detoxified repeatedly but not as severe as in people with an<unk>  use disorder who have no history of prior detox. Thus, the acute withdrawal syndrome appears to be the most important factor in causing damage or impairment to brain function. The brain regions most sensitive to harm from binge drinking are the amygdala and prefrontal cortex. People in adolescence who experience repeated withdrawals from binge drinking show impairments of long-term nonverbal memory. Individuals with an<unk>  use disorder who have had two or more<unk>  withdrawals show more frontal lobe cognitive dysfunction than those who have experienced one or no prior withdrawals. Kindling of neurons is the proposed cause of withdrawal-related cognitive damage. Kindling from repeated withdrawals leads to accumulating neuroadaptive changes. Kindling may also be the reason for cognitive damage seen in binge drinkers.
Alcohol withdrawal syndrome
Epilepsy
Benzodiazepine withdrawal syndrome
Drug withdrawal
Post-acute-withdrawal syndrome
Nicotine withdrawal
Opioid withdrawal
Cocaine intoxication