Effects of Alcohol Consumption on Various Systems of the Human Body: A Systematic Review PMC

Alcohol is the most commonly used recreational beverage and drug of abuse among the adult population, alcohol-related death is the third leading preventable cause of death in the United States which accounts for more than 3.3 million global deaths annually 1,2. According to the 2018-National Survey on Drug Use and Health (NSDUH), 14.4 million people suffered from alcohol use disorder (AUD) in the US, and over 100,000 deaths were attributable to alcohol 3. The World Health Organization reported that more than 200 health conditions including cancer, liver cirrhosis, and neurocognitive impairment were also attributed to alcohol consumption 2. These chronic health conditions are progressive, cause a heavy economic burden to society, and decrease the quality of life for both patients and caregivers 4. Among those who drink regularly, the prevalence of prescribed sedative-hypnotic use increased and prescribed opioid use remained common. These trends indicate that a substantial portion of the population is at risk for alcohol-related adverse drug reactions – particularly those age 40 and older.

This approach, known as the Sinclair Method, aims to reduce drinking by having people take naltrexone when consuming alcohol. Drinking can be harmful to anyone, regardless of their susceptibility to alcohol misuse or dependence. Therefore, the Center for Disease Control and Prevention (CDC) recommends avoiding excessive drinking, whenever possible, including binge drinking, heavy drinking, or drinking if you’re pregnant or younger than 21 years old. Drinking too much can lead to alcohol poisoning, respiratory failure, coma, or death. If you’ve experienced an overdose, you may experience mental confusion, vomiting, unconsciousness, slow heart rate, low body temperature, bluish skin, and irregular breathing, among other symptoms. It acts on an inhibitory neurotransmitter known as gamma-aminobutyric acid (GABA).

In some societies, alcohol consumption is even accepted as part of normal social etiquettes. Alcohol is thus, all pervasive and is in this way is the most dangerous drug known to mankind. In the brain, alcohol increases stopping duloxetine cold turkey the neurotransmitter gamma-aminobutyric acid (GABA), which results in lower levels of anxiety, stress, and fear.

Thus, ethanol exposure results in BBB disruption by a complex immune-regulatory loop between BMECs and astrocytes. Evidence from animal models and cell culture reports further strengthens the idea that chronic excessive alcohol exposure downregulates the tight junction proteins (claudin, occludin, zonula occludens) which are responsible for maintaining BBB integrity 43. Both acute and chronic alcohol exposure can increase the production of ROS and enhance peroxidation of lipids, protein, and phosphorylation of mitochondria resulting in decreased ATP production by disrupting phospholipid-containing cell membrane structure 44. Astrocytes maintain the BBB integrity by forming paracrine interactions to coordinates the CNS blood flow and neural function between pericytes and CNS vasculature 45. Alcohol-induced tight junction disassembly is usually mediated via activation of expression protein kinase C (PKC) which subsequently allows toxic substances to enter the brain which in turn affects CNS homeostasis. Loss of astrocytes function to maintain the neurovascular coupling is not recovered by the proliferation of adjacent astrocytes resulting in long-term effect in neurovascular damage.

Severe symptoms

Depressants affect the neurotransmitter gamma-aminobutyric acid (GABA), which slows down your brain activity. This can lead to side effects such as relaxation, drowsiness, slurred speech, decreased inhibition, and problems with coordination. Underlying the brain changes and neuroadaptations are the reward and stress circuits of the brain. A neural circuit comprises of a series of neurons which send electro chemical signals to one another. An activated neuron sends chemical signaling molecules called neurotransmitters through the neural circuit which bind to specific molecules called the receptors. Depending upon the circuit involved, the binding of these neurotransmitters may cause excitatory or inhibitory signals to be passed further along the circuit.

What is central nervous system (CNS) depression?

1. It is believed that alcohol acts as an antagonist for the NMDA receptor, so in the case of AUD, it causes hypofunction of the NMDA receptor which may result in neuronal network impairment with loss of synaptic plasticity 60.
2. These include Naloxone for opioid overdoses and Flumazenil for overdoses of benzodiazepine.
3. ALDH converts acetaldehyde to acetate, acetate has further effects on brain including increase lipid peroxidation and free radicals production.
4. Several substances can depress the CNS, ranging from anti-anxiety and sleep medications to so-called recreational drugs, such as heroin.

Before discussing the effect of alcohol on BBB damage, we have to look through alcohol absorption and metabolism. The liver is the predominant organ for ethanol metabolism which usually occurs via two oxidative pathways mediated by alcohol dehydrogenase (ADH) and cytochrome P450 2E1 (CYP2E1) 30 (Figure 1). In brief, after drinking alcohol, absorption Occurs in the gastrointestinal tract then the liver converts the alcohol to acetaldehyde through the first-pass metabolism in the liver, this oxidation reaction is catalyzed by the alcohol dehydrogenase enzyme 31,32.

Alcohol affects innate immunity and also interferes with almost all the various aspects of the adaptive immune response. Alcohol is a key player in impairing anti-inflammatory cytokines and also promotes proinflammatory immune responses. The gastrointestinal biome is severely manipulated by the use of alcohol over a long period of time, which in turn is found to have a link with the establishment of various complications 27. Alcohol and its metabolites are found to promote inflammation in the intestines and they do so through varied pathways 28.

More on drugs and other substances

GABA as a neurotransmitter has been long known to be affected by alcohol consumption. Recently, two sub types of the GABAA receptor have come into the spotlight for showing what can possibly be a genetic predisposition to alcohol addiction. These two subtypes are namely GABA A receptor α1 (GABRA1) and GABA A receptor α6 (GABRA6). The gene encoding GABRA1 is located on chromosome 5 at 5q34-35 while the how to make yourself pee gene encoding GABRA6 is located on the same chromosome at 5q34. According to a study by,62 a significant correlation was found with the GABRA1 genotype and Collaborative Study of the Genetics of Alcoholism (COGA) AD, history of blackouts, age at first drunkenness as well as the level of response to alcohol.

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