Introduction to Alcohol

Alcohol, in this context, refers to preparations of ethanol created for human consumption, usually in alcoholic beverages, to achieve intoxicating, psychoactive effects. It acts as a central-nervous-system (CNS) depressant, binding to the GABA-A receptor, with effects ranging from relaxation and euphoria at lower doses to loss of coordination and motor skills, unconsciousness and even death. Prolonged, regular use can lead to increased tolerance and addiction. Alcohol has a long history of human use and is one of the first documented drugs to be used by mankind, as well as being one of the simplest drugs to create structurally. Many different preparations have been produced, including beers; which are made via fermentation of sugar by yeast, whiskey, vodka and other 'spirits'; which are produced by fermentation and distillation, Everclear; which is ethanol distilled to its azeotropic limit, as well as wines, malt liquors, and champagne.

Using Alcohol

Alcohol is usually consumed for recreational purposes in the form of a beverage, falling into one of three distinct categories; beers, wines, or spirits. It is usually mixed with a certain amount of water and other flavourings, often owing to the method of production.
Alcohol may also be consumed for religious purposes, with certain Christian and Jewish sects using wine during religious ceremonies.

Ways of administration:

There are numerous ways to administer alcohol. Some conventional and some a bit unconventional. The most common is oral.

Oral

The most common method of consumption. Simply drunk as a beverage, alcohol is later absorbed through the lining of the stomach and small intestine.

Sometimes, and especially associated with binge drinking, alcohol will be consumed as quickly as possible either by drinking quickly, using a tube to speed transfer into the stomach.

Too much alcohol consumed orally, either large quantities over time or too quickly over a short period, may result in closing, of the pyloric sphincter. This prevents additional alcohol passing into the digestive system and generally results in vomiting. This is a basic defense mechanism of the body to prevent alcohol poisoning.

An example of one serving of Alcohol

Inhalation

Although this method is rare, it does indeed exist. Occasionally alcohol is vaporized and inhaled. Examples include inhalation of vapors from hand sanitizers (which often contain about 62% ethanol) and masks a user can wear to inhale the vapors of ethanol heated past its boiling point.

Intravenous

While possible, this is not recommended. From user reports, this can be quite painful. Additionally, some of the impurities which would be filtered out by the digestive system are introduced directly into the bloodstream.

Ocular

This is a very unusual and unorthodox method of administration. Needs more detail here, but there was a news story about this being all the rage at some college campus parties.

Can be irritating and quite damaging on the eye and surrounding mucous membranes.

Rectal

Some users are known to administer alcohol rectally. This speeds absorption avoids some first pass metabolism, but can be very irritating on mucous membranes of the large intestine and the bowel.[1]

However administrating alcohol rectally is very dangerous due to over-dosing easily from a very small amount.

Effects of Alcohol

Alcohol predominantly affects the gamma-aminobutyric acid (GABA-A) receptor, increasing the effects of the inhibitory neurotransmitter GABA, similar to other sedative-hypnotic drugs such as Chloral Hydrate or benzodiazepines. It also affects NMDA receptors.

The overall short-term effects of drinking alcohol are highly dependent on dosage, with higher doses increasing the occurrence of negative side-effects. Light to moderate drinking causes:

• euphoria
• increased self-confidence
• willingness to socialize
• inhibited judgment
• sedation
• analgesia
• impaired concentration/memory
• delayed reactions
• blurred vision
• difficulty balancing
• excessive urination

Progressively higher doses increase many of these effects and can cause:

• slurred speech
• mood swings
• dizziness
• double-vision
• nausea
• vomiting
• decreased heart rate
• urinary incontinence
• amnesia
• respiratory depression

Dangerously high doses can cause unconsciousness, coma, and even death.

Long-term effects of alcohol use include habituation, dependence, and addiction as well as liver disease, cancer and heart disease. Occasional mild use of alcohol is believed to help prevent cardiovascular disease. Alcoholism can be passed on through genes and therefore people whose family tree has had a lot of alcoholics are at higher risk for alcoholism as well as a higher natural tolerance to the effects of alcohol intoxication. Alcohol users experience most euphoria at low doses, at medium doses euphoria becomes confusion, and at heavy doses, a user reports to feel sick. After 300ml of 40% alcohol containing beverages, a hangover can present. This always causes BAC to be a little bit above legal driving limit. After binging on Alcohol, hangovers can sometimes persist up to 2 days.

Combinations with Alcohol

Alcohol can be particularly dangerous to combine with other drugs because it can cause a synergistic effect with many drugs. Alcohol is known to increase respiratory depression in combination with opiates and causes a stronger intoxication when combined with marijuana, which can often include the spins and other effects. Many narcotic pharmaceuticals can cause a life-threatening reaction in combination with alcohol.

Different Uses for Alcohol

In smaller amounts, alcohol is said to increase metabolism of heavy foods. In many countries, therefore it is acceptable even at younger ages to drink a glass of wine during or after a large meal.

It has also been theorized that alcohol may aid in cleaning out THC from one's body. THC is not water-soluble and is stored in fat cells. Drinking water therefore really doesn't do much to clean one's system of the drug. However THC is at least mildly soluble in alcohol, therefore drinking (but of course not to excess) a few days before a drug test could increase one's chance of passing.

Pharmacology of Alcohol

LD₅₀ (g/kg) :
Young rat : 10.6 orally
Old rat : 7.06 orally

1.INTRODUCTION​

Imagine yourself going for a couple of drinks after a long day at work.Not very long after finishing your single malt scotch (assuming you're not a heavy drinker) , you notice your state of mind begin to change.You think slower, have a lower reaction time, decreased coordination and slurred speech begins to set in and you begin acting more impulsively.A sense of warmth and mild euphoria is also noticed, and it's this effect that has been sought in the thousands of years since the discovery of fermentation.



But how does this actually happen?Why does alcohol affect people so differently?And why are some people "lightweights" while others can hold their liquor?

The answer to those and other questions can be found in the following sections.

2. WHAT IS ALCOHOL?​

There are several alcohols, but I'll only mention the two that are relevant to the discussion: Ethyl alcohol or Ethanol (drinking alcohol) and methyl alcohol or Methanol (wood alcohol).

Ethanol has only two carbon atoms, 5 hydrogens and a hydroxyl group (OH).This is the type of alcohol that is in alcoholic beverages.



Methanol has a simpler molecular structure, with only one C atom instead of two, and is sometimes the by-product of clandestine/improper distillation. It's metabolites include formic acid and formaldehyde, and drinking enough will cause blindness, coma, and death.

To ensure that the methanol is removed, legitimate distillers will throw away the first portion of the distilled product, since methanol has a lower boiling point than ethanol and therefore vaporizes first.

3. ABSORPTION AND METABOLISM OF ALCOHOL​

Before going into the more interesting part, you need to understand the ABCs of the absorption, metabolism, and distribution of alcohol.I must admit, it is a complex topic for those unfamiliarized with the subject, but I've made sure to include all necessary information for the understanding of how alcohol works, in a clear, reader-friendly and concise manner.

3.1 ABSORPTION​

Ethanol is a pretty small molecule that forms no ions and is insoluble in lipids and yet it's easily absorbed, and readily enters the brain.Due to its rather variable pharmacokinetics, the effects can't be described very accurately based on the amount ingested and so they're measured based on the amount that is in blood alcohol concentration (BAC).

Absorption occurs mainly in the intestine, and in much smaller part in the stomach.It crosses these membranes through a process called passive diffusion, which is the process through which substances flow from the side of the membrane with the highest concentration to the side with the least, which in this case involves the higher concentration of alcohol in the stomach/intestine and the lower concentration in the blood stream as shown bellow:



This means that the more concentrated the drink, and the faster its drank, as common sense would have it, the faster it diffuses into the bloodstream.Food delays the alcohol from getting into the intestine, and milk seems to delay absorption especially well.

3.2 METABOLISM​

Alcohol is metabolized primarily in the liver before being excreted as water and CO2 in the urine (about 95%) with the other 5% being excreted through the lungs.This is why cops can estimate your BAC using a breathalyzer test.

Alcohol metabolism is fairly constant independently of blood levels, and so if a person drinks faster than what can be metabolized, intoxication occurs.There are two enzymes that are extremely important for alcohol metabolism: Alcohol dehydrogenase and acetaldehyde dehydrogenase (ALDH).

First, alcohol dehydrogenase converts alcohol to acetaldehyde, an intermediate metabolite that is in significant part responsible for the hangover experienced after significant alcohol intake.This enzyme is found in the stomach, where it is 60% more active in men than in women, leading to a higher concentration that will have a faster absorption rate in women.

Certain medications such as aspirin and cimetidine can impair gastric metabolism, increasing absorption.
Once metabolized into acetaldehyde, it is quickly modified by the enzyme acetaldehyde dehydrogenase to form acetic acid.Drugs like disulfiram (Antabuse) inhibit this enzyme, inducing acute alcohol sensitivity, meaning that if someone drinks while taking the drug, they will suffer extreme hangover symptoms within 10min. which include nausea, vomiting, and a wicked headache.For this reason, the drug is often used to manage alcoholism.

This two step metabolic process is shown in this diagram:

Alcohol dehydrogenase ____________ALDH ____________________Oxidation

Alcohol -------------------Acetaldehyde--------------------acetic acid---------------------CO2 and H2O

Other enzymes such as cytochrome P450 also have a role in the metabolism of alcohol and many prescription drugs, which is why so many drugs interact with alcohol.

4. ALCOHOL PHARMACODYNAMICS: HOW DOES ALCOHOL WORK?​

We all know what effects alcohol has on our minds. But how does it happen? In this section, I go into what alcohol actually does to get you drunk.Keep in mind that no neurotransmitter system works by itself, and what affects one will indirectly affect others.

Alcohol is different than most drugs because it influences the phospholipid bilayer of neurons.This has a huge impact on the normal functioning of cells and this leads to a change in several neurotransmitter systems.I describe those changes in this chapter.

4.1 GLUTAMATE​

Glutamate is the main excitatory ("stimulant") neurotransmitter in the brain.Alcohol inhibits a type of glutamate receptors known as the N-methyl-D-asparate (NMDA) receptors which mediate memory and associative learning.They are ligand-gated channels that allow Ca2+ and NA+ through to cause depolarization.Alcohol inhibits these receptors by reducing the effectiveness of glutamate in the receptor.This explains, in part, alcohol's effects of learning and memory.

4.2 GABA​

GABA, as opposed to glutamate, is the main inhibitory neurotransmitter in the brain.GABA stands for Gamma-aminobutyric acid and it's the target of many sedatives and hypnotics including benzodiazepines like diazepam (Valium).Alcohol opens the Cl- channel in the GABA-A subtype which produces hyperpolarization on the membrane.Repeated agonism of this receptor leads to downregulation, but more on that later.

4.3 DOPAMINE​

Pretty much every drug of abuse has a direct or indirect effect on the dopaminergic pathways.It is directly linked to the pleasure centers of the brain, which have always had a very important role as they are behind all of our motivations, no matter how basic or intuitive.For example, dopamine is what makes you feel good when you have sex, drink water after being thirsty, or win the lottery.It's what makes your favorite food taste good and make you enjoy your favorite tv show, and alcohol, like all recreational drugs, has significant effects on this neurotransmitter.

One interesting fact that confirms it's role in addiction is that when dopamine antagonists (blockers) are injected directly into the mice brain areas associated with pleasure and reward it significantly reduces their consumption of alcohol.

4.4 OPIOID SYSTEMS​

When scientists first discovered the opiate receptors, they were confused as to why we'd have receptors for morphine, a substance only found in the opium poppy, in our brain.After much thinking, the only conclusion that could be drawn was that morphine-like substances must be produced in our bodies that fit the same receptors and have a role in anxiety and pain reduction.These substances were eventually found and named "endorphins" and "enkephalins".

Alcohol induces the release of these endogenous opioids, which contribute significantly to it's rewarding and pleasurable effects.As to prove this statement, opioid receptor antagonists (blockers) were given to rats along with their alcohol, and this significantly decreased their consumption.

5.ALCOHOL TOLERANCE: HOW DOES IT OCCUR?​

Everyone knows that the more and the longer you drink regularly, the more you need to drink to reach the same effect.This has no one single mechanism, and instead, is a combination of different factors that in combination create tolerance to alcohol:

5.1 Metabolic changes​

Prolonged consumption of alcohol leads to an increase in alcohol dehydrogenase and other enzymes that contributes to a more rapid metabolism of the drug.

5.2 Receptor regulation​

As explained earlier, alcohol has effects on several neurotransmitter systems and their combined regulation is in part, responsible for tolerance to alcohol:

GLUTAMATE (NMDA): As alcohol inhibits or antagonizes this receptor, the expected response is upregulation.This means that NMDA receptors increase in number over chronic exposure to alcohol, making it less effective in its action.

GABA: As explained earlier, alcohol acutely increases the Cl- influx at the GABA-A receptor, but chronic exposure to the drug has the opposite effect.Normal Cl- influx decreases at this receptor, making it less sensitive to the effects of alcohol.

DOPAMINE: Opposite to acute effects, animals that have been chronically exposed alcohol show severely reduced dopaminergic firing in the ventral tegmental area and nucleus accumbens, both areas being strongly involved in reward and pleasure.

ENDOGENOUS OPIOID SYSTEMS: Chronic alcohol consumption reduces gene expression responsible for endorphin and enkephalin release from the pituitary gland, causing chronic dysphoria and further tolerance tot he drug.

5.3 BEHAVIORAL TOLERANCE​

We've all met or heard about the office drunk who is completely smashed 24/7 and yet acts pretty normal, even getting their work done.How can they do this? The answer is behavioral tolerance.

An interesting experiment was done on mice that were chronically fed alcohol and then made to run on a treadmill.They were pretty unsuccessful in the beginning, but surely enough they soon began running on the treadmill almost as well as rats that were given alcohol after running on the treadmill (as to eliminate other alcohol-related factors).

6. DIFFERENCES IN PHYSIOLOGICAL RESPONSE: WHY AM I A LIGHTWEIGHT?​

We've all met someone who can outdrink the best of us, and now that we understand the basics, we can begin to understand why people react so differently to alcohol, and why sex, age, race and genetic makeup matter so much.

Although most certainly a factor, lack of tolerance to alcohol is not always the reason some people get smashed on two cans of beer, while others can drink pint after pint without puking all over your floor.In this section, I'll explain how people are different when it comes to tolerating booze.

It would not surprise the reader to hear that women have a lesser tolerance to the effects of alcohol than men.But what the reader may not know is that alcohol dehydrogenase is 60% less active in the gastric fluid of a woman than in that of a man.This obviously leads to a faster absorption, and therefore a higher peak alcohol concentration.

Racial differences in alcohol metabolism are somewhat harder to explain, but put simply, involve differences in the acetyldehyde dehydrogenase (ALDH) gene.As discussed earlier, when this enzyme is blocked by the drug disulfram, alcohol consumption produces an instant severe hangover accompanied by flushing.

Everyone has a pair of chromosomes with the ALDH gene, one from the mother and one from the father.The two chromosomes can either be formed by the same pair of the same gene (alleles) or two different alleles.

These alleles, individually, can be either active or inactive.This means that someone with two active alleles have normal metabolism of acetaldehyde and will tolerate alcohol well, while someone with two inactive alleles will experience severe flushing, nausea, and vomiting with amounts of alcohol that would be perfectly tolerable to most people as they are unable to properly metabolize acetaldehyde.Alternatively, someone may have one active and one inactive ALDH allele which produces a response to alcohol somewhere in between the previous two cases.

Most people of Asian descent inherit genes that encode only the inactive form of the enzyme, or only one active form, making them either very susceptible to alcohol's effects (in the first case) or otherwise more susceptible than most people.The latter can have a lower vulnerability to alcoholism.

Metabolism of Alcohol

Alcohols are oxidized in the body to their corresponding aldehydes or ketones by the enzyme alcohol oxidase. This enzyme oxidizes ethanol into acetaldehyde, which is responsible for many of the negative side-effects of alcohol consumption. Acetaldehyde is readily converted into acetic acid (the same acid found in vinegar) upon reaction with water from the body. Failure to stay hydrated while drinking alcohol prevents the conversion of acetaldehyde to acetic acid and causes a number of negative side-effects attributable to both dehydration and acetaldehyde intoxication. These can include headaches, sensitivity, lethargy, dysphoria, thirst, mild depression, and anxiety. Acetaldehyde intoxication can often be noted by a mildly fruity odor on one's breath.

Acetic acid formed via ethanol metabolism increases the acidity of the stomach often causing a sour stomach feeling and, in high enough amounts, can cause nausea and vomiting as well as diarrhea and other negative effects.

Chemistry of Alcohol

Column 1	Column 2
Systematic (IUPAC) name:	ethanol
Synonyms:	ethyl alcohol, absolute alcohol, anhydrous alcohol, dehydrated alcohol, ethyl hydrate, ethyl hydroxide
Molecular Formula:	C2H6O
Molar mass:	46.07 g/mol
CAS Registry Number:	64-17-5
Melting Point:	-114.1°C
Boiling Point:	78.5°C
Flash Point:	13°C (closed cup)
Solubility:	miscible with water and many organic liquids
Additionnal data:	density (20°C) 0.789
Notes:	clear, colorless, very mobile, pleasant odor, burning taste

[1]

The terms 95% alcohol and alcohol refers to a binary azeotrope consisting of 95.57% ethanol and 4.43% water (by weight) and having a boiling point of 78.15°C. Alcohol, USP designates a mixture of ethanol and water, with ethanol content (by weight) between 92.3 and 93.8% (94.9-96.0% by volume at 15.56°C, 60°F). Diluted alcohol is preparated from equal volumes of 95% alcohol and water, contains about 41.5% ethanol by weight, 48.9% by volume (density 0.931 @ 25°C, 0.936 @ 15.56°C).

The dangers of Alcohol

Alcohol is one of the more dangerous drugs in our society, despite being more socially accepted than many other, safer drugs such as marijuana, ecstasy, and hallucinogens such as magic mushrooms.

Drunk Driving

Alcohol lowers response time, attention span, judgment, impairs senses and increases risk-taking. For this reason, alcohol consumption can be very dangerous while driving or operating heavy machinery. Since the act of driving drunk puts other drivers' lives at risk, many states and countries have a zero-tolerance policy for drunk driving including heavy fines, license suspension/revocation and even jail time for those caught driving under the influence. In many places, the legal Blood-alcohol-content limit is .08, and police officers may carry breathalyzers to test for alcohol intoxication. This cannot easily be broken down into how many units is safe as we all process alcohol differently. A very rough guide is that 3-4 units will bring most men to the limit and 3 for most women. This basically means 1 drink (low strength) should keep one under the limit. People should always wait at least an hour after a drink before driving or operating any machinery.

Police may also in some places give you a DWI if you are operating a bicycle or other form of transportation while under the influence of alcohol.

There is no foolproof way of drinking and staying under the limit. The amount of alcohol you would need to drink to be considered driving under the influence varies from person to person. It depends on:

• Your weight
• Your gender (men tend to process alcohol faster than women)
• Your metabolism
• Your current stress levels
• Whether you've eaten recently
• Age (younger people tend to process alcohol more slowly

Bear this in mind when driving the following day. If you have had a heavy session drinking, you may still be over the limit although you may feel sober. A general rule of thumb is that it takes us roughly 1 hour to process 1 unit of alcohol if you go to sleep this slows down to about 1 ½ hours per unit. This is again affected by the factors in the list above.

So if you drink 6 pints of Becks lager (5%) at 2.8 units per pint, this will take about 17 hours to be back down to nothing and longer if you have went to sleep for a few hours.

Alcohol poisoning

Alcohol poisoning is a risk when consuming large amounts of alcohol in one sitting, it is particularly associated with binge drinking. The signs are:

• Confusion
• Loss of coordination
• Vomiting
• Seizures
• Irregular or slow breathing (less than eight breaths a minute)
• Blue-tinged or pale skin
• Low body temperature (hypothermia)
• Stupor (being conscious but unresponsive)
• Unconsciousness (passing out)

Producing Alcohol

The most common method of producing alcohol is via fermentation of sugar by yeast, a eukaryotic fungus. The yeast breaks down sucrose into simple alcohols and CO2, and in the process produces a beer-like solution which contains both methanol and ethanol. As-is, this mixture can be poisonous as methanol's metabolites (formaldehyde and ultimately formic acid) are corrosive and toxic to humans. Therefore when distilling the alcohol, the first bit that spills over (containing mostly methanol) is thrown away.

Forms of Alcohol

Harm reduction advice for alcohol

Your body takes roughly an hour to process 1 unit of alcohol. Guidelines in the UK suggest safe daily amounts for alcohol are 2-3 units for women (equivalent to a 175ml wine glass) and 3-4 units for men (equivalent to a pint and a half of beer). The National Health Service (NHS) in UK explain binge drinking as anything over 8 units of alcohol for men– or about three pints of strong beer. For women, it’s drinking more than 6 units of alcohol, equivalent to two large glasses of wine. There have been studies to show that drinking a large amount of alcohol over a short period of time may be significantly worse for your health than frequently drinking small quantities. So drinking occasionally but heavily isn't any better for you. Most importantly guidelines state you need at least 2 days without any alcohol to let your body recover. Some tips to reduce your alcohol use are:

• Drink spacers (non- alcoholic drink in between drinks), a non-carbonated drink is generally best as fizzy drinks can help you absorb alcohol more quickly.
• Avoid getting into rounds in pubs or clubs, this generally encourages you to drink more to keep up with peers
• Drink bottles of beer, half pints or shandy rather than pints also consider low strength beer
• If you drink spirits-try and pour your own drink if you're drinking in the house and measure it out so you can keep track (use a shot glass/egg cup/lid to measure)
• Eat well before you go out and have snacks as that generally helps slow down alcohol consumption. Be careful with very salty foods as this tends to make you thirsty.
• Avoid mixing drinks, most people tend to find consuming lots of different types of drinks can make them more likely to feel rough. You are perhaps more likely to drink more alcohol than you intend if you are mixing. For example if you have 10 beers, you will probably notice a lot more how much you have had than if you have a few beers, a couple of shots, then some spirits with mixer
• Take out a set amount of money with you and leave your bank card at home.
• Alcohol withdrawal causes hallucination, delirium and paranoia in alcoholics. It is very dangerous to quit cold turkey, if this is the case. It's a medical emergency and you should call 911

Legal status of Alcohol

Alcohol is legal in many industrialized nations, despite its overall negative effects on society and health compared to other (mostly illegal) drugs. There are many restrictions on its consumption and use. In many places the legal drinking age is 21, whereas in places such as France where drinking during/after dinner is socially accepted, restaurants may serve alcohol to citizens as young as 16. In some places it is unlawful or socially unacceptable to be drunk in public, and in most places it is illegal to drive or operate heavy machinery under the influence of alcohol.

Some Islamic nations have criminalized the use of alcohol (or for that matter any intoxicating substance) inside their country's limits for religious or other legal reasons. Penalties for use in these countries may be severe.

United Nations

USA

The USA has an interesting legal history of alcohol. During the 1920s, the US government decided to place a prohibition on alcohol consumption, effectively pushing the entire market underground. The result was increased crime including murder, health risks due to impurities found in alcohol, and the formation of an untaxed, underground market for alcohol. Clandestine moonshine distilleries began popping up, wherein the fermentation and distillation process was done in secrecy - much like a clandestine drug operation runs today. Individuals (the most famed is Al Capone) began making lots of money producing and smuggling alcohol across the country. During this time, the Great Depression began hitting the American people hard. The prohibition ended on March 23, 1933 when President Franklin Roosevelt signed an act repealing the prohibition. Upon signing, he famously stated "I think this would be a good time for a beer." The Great Depression ended not long after the repeal of alcohol prohibition. This prohibition in many respects has a lot of similarities to marijuana prohibition the way it is now.

Some counties/parishes/states in the United States have placed restrictions on where to get alcohol and the times which alcohol can be obtained. Unrestricted counties may sell all forms of alcohol (to legal-age customers) in grocery and convenient stores while others may limit the sale to sites specifically made to sell alcohol. These 'stores' may often close at a certain time and may not be open on Sundays, for religious or other reasons. In other counties, the sale of alcohol may be prohibited altogether (in what is known as a 'dry' county.)

EU

Islamic Countries

History of Alcohol

More Alcohol Sections