THE PHARMACOLOGY OF ALCOHOL
How Alcohol Affects The Brain and Body
Following ingestion, alcohol is rapidly absorbed by the gut and enters the bloodstream with a peak in blood alcohol concentration after 30 to 60 minutes.
Alcohol is then distributed around every part of the body. It readily crosses the blood–brain barrier to enter the brain, where it causes subjective or psychoactive and behavioural effects, and, following high levels of chronic alcohol intake, it can cause cognitive impairment and brain damage.
Alcohol is excreted in urine, sweat and breath, but the main method of elimination from the body is by metabolism in the liver, where it is converted to acetaldehyde and acetate. These metabolites are then excreted from the body, primarily in the urine.
The rate at which alcohol is metabolised and the extent to which an individual is affected by a given dose of alcohol is highly variable from one individual to another. These individual differences affect drinking behaviour and the potential for alcohol-related harm and alcohol dependence.
Also, the effects of alcohol vary in the same individual over time depending on several factors, including whether food has been consumed, rate of drinking, nutritional status, environmental context and concurrent use of other psychoactive drugs. Therefore, it is very difficult to predict the effects of a given amount of alcohol both between individuals and within individuals over time.
For instance, the impact on the liver varies clinically so that some experience liver failure early on in their drinking career, whilst in others, drinking heavily, liver function is relatively normal.
A Toxin That Creates Dependence
Alcohol is a toxic substance, and its toxicity is related to the quantity and duration of alcohol consumption. It can have toxic effects on every organ in the body.
In the brain, in a single drinking episode, increasing levels of alcohol lead initially to stimulation (experienced as pleasure), excitement and talkativeness. At increasing concentrations, alcohol causes sedation leading to sensations of relaxation, then later to slurred speech, unsteadiness, loss of coordination, incontinence, coma and ultimately death through alcohol poisoning due to the sedation of the vital brain functions on breathing and circulation.
The dependence-producing properties of alcohol have been studied extensively in the last 25 years. Alcohol affects a wide range of neurotransmitter systems in the brain, leading to the features of alcohol dependence.
“The effects of alcohol withdrawal can take up to between 3 months and 1 year to fully recover from (referred to as the protracted withdrawal syndrome).”
Alcohol And The Brain
The main neurotransmitter systems affected by alcohol are gamma-aminobutyric acid (GABA), glutamate, dopamine and opioid.
The action of alcohol on GABA is similar to the effects of other sedatives, such as benzodiazepines (including Valium), and is responsible for alcohol’s sedating and anxiolytic properties.
Glutamate is a major neurotransmitter responsible for brain stimulation, and alcohol affects glutamate through its inhibitory action on N-methyl D-aspartate (NMDA)-type glutamate receptors, producing amnesia (for example, blackouts) and sedation.
Chronic alcohol consumption leads to the development of tolerance through a process of neuroadaptation: receptors in the brain gradually adapt to the effects of alcohol to compensate for stimulation or sedation. This is experienced by the individual as the same amount of alcohol has less effect over time. This can lead to an individual increasing alcohol consumption to achieve the desired psychoactive effects.
“This is experienced by the individual as the same amount of alcohol having less effect over time. This can lead to an individual increasing alcohol consumption to achieve the desired psychoactive effects.”
The key neurotransmitters involved in tolerance are GABA and glutamate, with chronic alcohol intake associated with reduced GABA inhibitory function and increased NMDA-glutamatergic activity. This GABA–glutamate imbalance is acceptable in the presence of alcohol, which increases GABA and reduces NMDA-glutamate activity.
However, when the alcohol-dependent individual stops drinking, the imbalance between these neurotransmitter systems results in the brain becoming overactive after a few hours leading to unpleasant withdrawal symptoms such as anxiety, sweating, craving, seizures and hallucinations. This can be life-threatening in severe cases and requires urgent medical treatment. Repeated withdrawal is also thought to underlie the toxic effect of alcohol on neurons, leading to cognitive impairment and brain damage.
The effects of alcohol withdrawal can take up to 3 months and 1 year to fully recover from (referred to as the protracted withdrawal syndrome). Even then, the brain remains abnormally sensitive to alcohol, and when drinking is resumed, tolerance and withdrawal can return within a few days (known as reinstatement). This makes it extremely difficult for a person who has developed alcohol dependence to return to sustained moderate drinking.
Dopamine & Alcohol
The brain’s endogenous opioid system is also affected by alcohol. Alcohol stimulates endogenous opioids, which are thought to be related to the pleasurable, reinforcing effects of alcohol. Opioids, in turn, stimulate the dopamine system in the brain, which is thought to be responsible for appetite for a range of appetitive behaviours, including regulation of appetite for food, sex and psychoactive drugs. The dopamine system is also activated by stimulant drugs such as amphetamines and cocaine, and it is through this process that the individual seeks more drugs or alcohol. There is evidence that drugs which block the opioid neurotransmitters, such as naltrexone, can reduce the reinforcing or pleasurable properties of alcohol and so reduce relapse in alcohol-dependent patients.