Courtesy of http://blogs.telegraph.co.uk/news/edwest/100146529/minimum-alcohol-pricing-not-an-absolutely-terrible-idea/

Alcoholism or alcohol addiction is defined as having a psychological and physical dependency on alcohol. In the United States alone, an estimated 20 million people are classified as alcoholics[1] . Everyone has the potential to become an addict however some are more vulnerable than others as a result of various factors including both controlled and uncontrolled factors[2] . Alcohol (ethanol) toxicity to the brain leads to both structural and molecular changes causing a dual disease that has physiological and psychological effects [3] .


Due to higher accessibility to alcohol than other drugs, individuals with a vulnerability to addiction tend to become alcoholics. Among both men and women, there is a higher number of women addicted to alcohol[4] . This may be due to women metabolizing ethanol at a faster rate than men however, it is not clear as to why this is the case. Poor diet can also increase an individuals risk especially in those with thiamine deficiency[5] . Other factors that contribute to a person's susceptibility include age, race, level of education, drinking history, and genetics[6] .

Adolescent Brain

Adolescents and young adults are more susceptible to ethanol exposure as a result of social experimentation[7] . The young brain is highly plastic and constantly rewiring and pruning throughout adolescence towards early adulthood. This heightened state of neuroplasticity is associated with a greater risk and vulnerability towards social addictions. Although ethanol is often associated with learning and memory deficits, abuse is also as likely to cause the opposite effect, resulting in an established learned association towards alcohol. The maladapted synaptic connections displayed in individuals with excessive ethanol exposure can become stabilized in youth. This can follow them into adulthood when the brain is more persistent and less resistant to change. Social addictions found in adults are often manifested in adolescence where over 80% of alcoholism cases begin before the age of 30[8] .

Experimentation with alcoholism in adolescent rats have also shown a higher tolerance level to acute ethanol exposure, which may be attributed to the brain's heightened plasticity[9] . This higher tolerance level further promotes ethanol consumption.

Environmental Association

A person’s cultural environment can affect an individuals susceptibility to alcoholism. Individuals born into traumatic and stressful environments, mostly low socioeconomic status neighborhoods, show significantly higher rates of alcoholism. A person’s environment also influences their diet subsequently affecting their nutritional intake. In particular, thiamine deficiency contributes to cognitive deficits leading to increased vulnerability to alcohol addiction[10] .

Genetic Variation

A persons family history and genetics contribute to the individuals risk of becoming an alcoholic. Genetics determine someone's vulnerability, metabolism, and tolerance level with ethanol while also affecting the receptors and transporters for neurotransmitters such as glutamate, GABA, dopamine and NMDA which are associated with withdrawal symptoms [11] [12] . Individuals that have an alcoholic family member have a tendency to begin drinking at a younger age and have a higher risk of becoming alcoholics [13] . Pre-exposure to ethanol before birth causing fetal alcohol syndrome, affects the general health of an individual and is also a neuropsychiatric risk.

Physiological Signs and Symptoms

Ethanol is a lipid soluble compound therefore, it is able to cross the blood brain barrier affecting brain functions and with long term use, cause structural changes. In moderate drinkers (less than three drinks per week), neither current nor life time intake of ethanol causes any significant changes to the brain [14] . However, when ethanol is abused, brain modifications can occur altering one's mental state.
Courtesy of http://www.smart-kit.com/s545/your-brain-on-alcohol/

Etiology of the Brain

The most common neurological ethanol-related structural change is brain atrophy. Predominately in the white matter, experiments show that there is a negative correlation between maximum ethanol consumption and the amount of white matter loss[15] [16] . This can be caused by disrupting both myelination and axon integrity ultimately disrupting action potentials [17] . Specific areas of the brain are more sensitive to the effects of alcohol, one being the corpus callosum[18] . This commissure connecting fiber is a major white matter structure in the brain that is responsible for connecting the two cerebral hemispheres and allowing transmission of information between both hemispheres. Disruption of the corpus callosum (i.e shrinkage of fibers due to exposure of excessive alcohol) can disrupt cognitive performance in an individual [19] . Other areas of the brain that experience atrophy include the
cerebellum , also referred to as the “little brain”, plays a role in balance, coordination and executive functioning[20] . Clinical ataxia and unsteadiness is attributed to shrinkage of the pyramidal cells of the anterior-superior cerebellar vermis, a structure in the cerebellum[21] . The prefrontal cortex, responsible for judgement and problem solving, is also vulnerable to atrophy and is the cause of impulsivity resulting in “liquid courage”[22] .

Molecular Changes

Prolonged alcohol exposure can result in changes to molecular programming of the brain.


N-methyl-D-aspartate (NMDA) is a glutamate receptor involved in several different physiological processes including synaptic plasticity[23] . These tetrameric receptors, made of various NR1 and NR2 (A-D) subunits, are found postsynaptically along with other glutamatergic receptors.

Ethanol inhibits excitatory glutamatergic neurotransmitters and consequently inhibits NMDA receptors resulting in adaptive changes under prolonged exposure of ethanol [24] [25] . This indirectly results in inhibition of synaptic activity causing alterations in NMDA receptor trafficking to the post synaptic terminal. To maintain homeostasis, glutamate systems are up-regulated; increasing in size and number of NMDA receptors leading to neuronal excitability.

Constant ethanol exposure will also result in changes in NMDA subunit localization. The NR2B subunit, associated with experience dependent plasticity, is one of the subunits affected. This may attribute to the type of learning and memory involved with synaptic plasticity.

NMDA receptors not only affect dendritic spine morphology but plays a role in long term potentiation (LTP) and long term depression (LTD) involved in learning and memory[26] . Increased expression of NMDA receptors and phosphorylation of NR2B subunits is associated with LTP seen in alcoholics. In the absence of alcohol, ethanol induces changes to NMDA receptors, which reverses currents resulting in LTD.

Dendritic Spines
Carpenter-Hyland, E. & Chandler, L. Plasticity of NMDA receptors and dendritic spines: Implications for enhanced vulnerability of the adolescent brain to alcohol addiction. Science Direct 86: 200-208 (2007)

Dendritic spines are small protrusions of a dendrite filled with filamentous actin[27] . Typical mature spines have a thin stalk capped with a round head where signaling of synapses occurs. Spine morphology correlates with synaptic strength; larger heads restrict Ca2+ diffusion, making synapses more efficient[28] . Synapses are consistently being modified by intracellular and extracellular events. Synaptic modifications are dependent on Ca2+ influxes which are regulated by NMDA receptors[29] . Prolonged inhibition of synaptic activity, by alcohol, results in an increased clustering and size of spines to stabilize the neuronal network imbalance[30] . This is caused by enlargements of F- actin clusters increasing proportions of the spine size. Increase in dendritic spine size is only found in ethanol abuse individuals, not in acute exposure.

Physiological Effects

Ethanol not only affects the brain but all the other organs in the body. The most notable disease following ethanol abuse is cirrhosis of the liver[31] . The liver aids in breaking down and eliminating alcohol's toxic properties and with each period of ethanol consumption there is further damage to the liver.
Cirrhosis of the liver further causes nutritional deficiency leading to higher susceptibility to other disease. The pancreas is also directly affected by ethanol and damage may lead to jaundice. Other physiological effects include vomiting, sexual dysfunction, alcoholic, dementia, and epilepsy.

Wernicke-Korsakoff Syndrome

Ethanol abuse can lead to Wernicke-Korsakoff Syndrome, two disorders that are considered a continuum, which are caused by thiamine deficiency [32] . Wernicke encephalopathy, the acute phase, causes lesions to the periventricular regions of the brain which effects ocular movement, cerebellar functioning, mental state and memory. Korskaoff’s amnesic syndrome, the chronic phase, affects the anterior nucleus of the thalamus, involved with learning and memory. To reduce the cases of WKS, supplementation of thiamine in stable foods including bread have been implemented in the U.S and other countries.

Abstinence and Withdrawal

Abstinence, a period with no alcohol, can reverse some of the brain atrophy caused by ethanol[33] .The brain increases in size due to the metabolic and neurophysiological recovery as well as an increase of cerebellar choline and frontomesial N-acetylaspartate levels, which possess the ability to induce brain regrowth. Other neurotransmitters and receptors are restored to ‘controlled’ levels, such as NMDA receptors.

Withdrawal symptoms are caused by overactive glutamate receptors that are adapted to ethanol exposure[34] . Glutamate is a neurotransmitter that causes excitability but when exposed to ethanol, it interferes with glutamate affecting memory and causing “black outs”. The brain adapts and adjusts to the environmental and neuronal changes by increasing the number of glutamate receptor sites in the hippocampus. During abstinence, the glutamate receptors become overexcited and have been linked to neuronal death that can manifest as a stroke or seizure. Not only do glutamate receptors change but there is a decrease in GABA receptors, an inhibitory neurotransmitter, which also contributes to overexcitation of the brain when drinking is ceased. This causes a decrease in inhibition which also contributes to seizures experienced during the withdrawal phase.


Treatment for alcoholics is a step by step process; acute abstinence without any supplementation may cause fatal side affects. The type of treatment also varies among alcoholics as ethanol can affect people both mentally and physically.


Courtesy of http://www.counselor.org/therapeutic-counseling.html

Different types of therapy, such as family therapy or psychotherapy, can be used to treat not only alcoholism but other types of social addictions. Therapy helps alcoholics discover the potential underlying reasons for abusing ethanol as well as skills to prevent succumbing to withdrawal symptoms. Among the various forms of therapy, group therapy is popular among the alcoholics and involves gaining mutual help from others[35] . A well known establishment aimed to offer help similar to group therapy is Alcoholics Anonymous[36] .

Pharmacological Medication

There are various types of drug treatments that can help with different aspects of ethanol addiction. Three FDA approved drugs, in the US, include Acamprosate, Naltrexone, and Disulfiram[37] . Acamprosate reduces NMDA activity by blocking the effects of glutamate, in doing so this helps reduce ethanol-related neurotoxicity during the withdrawal phase [38] [39] . Naltrexone helps alcoholics from experiencing cravings; ethanol causes the body to release endorphins and dopamine and Naltrexone blocks these effects, being a competitive antagonist for opioid receptors [40] . Disulfiram prevents the elimination of acetaldehyde produced when ethanol is consumed[41] . Acetaldehyde is toxic to the body and a contributing factor to hangovers. Disulfiram causes ethanol consumption to be uncomfortable, similar to a hangover, causing a conditioned association of discomfort and ethanol to prevent drinking. These drugs only help prevent ethanol consumption and promote abstinence, however, are not a cure.


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