PSYC330: Alcohol (Ethanol)

History

1. Strong association with human society

   1. Fermentation is said to have developed in parallel with civilization

   2. Speculation that human alcohol use is linked evolutionarily to a preference for fermenting fruit 

      1. The presence of ethanol signals fruit is ripe but not yet rotten

2. The earliest records of distilled spirits appeared in China ~1000BC

   1. Alchemists were captivated by the invisible “spirit”

      1. Remedy for almost all diseases

   2. Whiskey is derived from usquebaugh

      1. Gaelic for “water of life”

      2. Became a major ingredient of many tonics and Elixirs

Alcohol- Types

1. Methyl (wood alcohol)

   1. Produced synthetically

   2. Antifreeze, fuel

2. Ethy (grain alcohol)

   1. Produced by fermentation

   2. The one people drink 

3. Isopropyl (rubbing alcohol)

Fermentation

1. Organic material with sugar content

2. Yeast (from the air) consumes the sugar 

3. 1 molecule of sugar consumed -> 2 molecules of alcohol + 2 molecules of carbon dioxide  

Distillation

1. A fermented beverage is heated to a vapor, which is then cooled 

2. What is the purpose of this?

   1. Become more concentrated!

Consumption changes across history

1. The average American drinker:

2. 1800s

   1. 4-5 standard drinks per day

3. Currently 

   1. 3-4 standard drinks per week

US Alcohol Use (2022 NSDUH)

1. The highest consumption is in the college-age group 

2. 48.7% (12 and older) drank in the last month 

3. 21.7% binge drink (4-5 more drinks on an occasion) in the past month

4. 5.7% engaged in heavy drinking (5 or more drinks on an occasion on 5 or more occasions per month) in the past month

5. Male and female drinking rates are converging- lifetime drinking in 12+: males (79.7%), females (77.3%)

6. The number of binge drinking days increases with age during adolescence 

Alcohol Content of Various Beverages

Beverage	% Alcohol	Proof (proof is double what the percentage of alcohol is)
Beer (*depends on the type of beer)	4-6	8-12
Wine	7-15	14-30
Spirits (hard liquors)	40-95	80-190

Alcohol Beverage Equivalents: Standard Drink Sizes

12 oz beer = 8-9oz of malt liquor = 5oz of table wine

Broad Scope

1. Economic burden >$200B / year

   1. Medical and social impacts

2. 100,000 deaths/year

3. 15.1 million (1:20) meet criteria for alcohol use disorder (2015)

   1. Diagnosis and treatment are often delayed until the disease is advanced

      1. Complicated by social and health issues -> difficult to treat 

4. Among the “diseases: with genetic and environmental influence

   1. Stigmas and moral failures impede the recognition and treatment of alcohol problems 

ADMET(T)

1. Large amounts are required for physiological effects

   1. Consumption is more like a food than a drug

      1. Serving size is about 14g in a typical better, glass of wine, or shot

      2. consumed/ dosage in grams qualities

Absorption

1. Oral route of administration

   1. Most common method

2. Inhalation

   1. AWOL (alcohol without liquid)

   2. Vaportini

   3. Higher blood alcohol levels (BALs) 

   4. Banned in most states 

3. Powdered Alcohol

   1. Approved in 2016

   2. Banned in 31 states

4. Why haven’t these other methods taken off?

   1. They are harder to control the amount being consumed  

5. Simple small molecule

   1. Soluble in water and lipids

   2. Neural particle- diffuses easily through membranes 

6. Rapidly absorbed into the bloodstream

   1. Stomach (slower) and small intestine (faster)

   2. Distributes into the total body water 

7. What about food in the stomach 

   1. It will slow down ethanol absorption -> lower BAL

Distribution

1. Weight

2. Gender

   1. The muscle/fat ratio is greater for men

3. Age

4. Distributed throughout the body

   1. ~90% reaches blood -> crosses Blood Brain Barrier

Blood Alcohol Level/Concentration (BAL/BAC)

1. Concentration of alcohol in blood

2. Metric measurements and percent

   1. BAL expressed in mg of alcohol per 100 milliliters (deciliter)

      1. Ex: 80mg/dL -> .08g/100mL ->.08%

   2. Legal limit is .08% (80mg/dL, ~17mM)

   3. A standard drink contains ~30mg/dL

Alcohol Metabolism in the Liver

Metabolism

1. Liver metabolizes majority of ethanol

2. Fatty acids build up in liver

   1. Leads to cell death

   2. Alcoholic fatty liver -> alcoholic hepatitis -> cirrhosis -> liver failure

3. Some breakdown in stomachs 

   1. Males > females

Excretion

1. ~2-8% unchanged through lungs

   1. Breathalyzers useful for determining BAL

2. 90-95% oxidized slowly (kidney)

3. Alcohol increases urination

   1. Ingestion of liquid 

   2. Suppression of antidiuretic hormone (ADH)

Pharmacodynamics- “Dirty Drug”

1. “Dirty” drug 

   1. It has many specific effects

   2. Can affect all cells in the body 

   3. An impact all systems in the body in specific ways 

2. Alcohol has a lot of very specific effects on binding sites and neurotransmitter receptors

Pharmacodynamics: Positive reinforcement reward system 

1. GABA interneurons synthesize and release GABA on the dopamine cell body, inhibits dopamine release so there isn’t too much firing at once 

2. Opioid Peptides regulates the GABA interneurons 

3. Alcohol has three specific effects in this system

Mechanism of Action

1. Our bodies and nervous system works to balance things to keep us at baseline

2. Alcohol has a specific effect on GABA and glutamate system 

3. Acute effects

   1. Alcohol enhances the GABA inhibitory system 

      1. More inhibition of the GABA system 

   2. Decreases excitation of the Glutamate system 

      1. Inhibiting the currents through glutamate (excitatory receptors)

   3. Shifts the homeostasis in one direction and it makes it confused and less likely to release action potentials 

4. Disturbs fine balance between excitatory and inhibitory influences

   1. Results in anxiolytics, amnesia, ataxia, and sedation

5. Number of putative sites of action have been identified

   1. Likely produces its effects by simultaneously altering function of numerous proteins that affect neuronal activity

Examples of Additional Sites of Action

1. Ligand-gated ions channels

   1. Nicotinic acetylcholine receptors

   2. Serotonin (5-HY3) receptors

2. Multiple metabotropic receipts

   1. Dopamine receptors 

   2. Opioid receptors

3. Voltage-gated channels

   1. Calcium channels

   2. Sodium channels

Behavioral effects 

Acute Intoxication (Non-Tolerant Individuals )

BAC g/dL	Clinical effect
0.05-0.1 (11-22mM)	Subjective high “buzz”, anxiolytics, sedation
0.1-0.2 (22-44mM)	Motor impairment, slurred speech, blackout
0.2-0.3 (44-66 mM)	Emesis (vomiting), stupor (near unconsciousness)
0.3-0.4 (44-88mM)	Coma
>0.5 (110mM)	Respiratory depression, death

*this is just average, in chronic alcohol users, 0.4 g/dL will not be lethal

Peripheral Effects

1. Dilates Blood Vessels 

2. Decreases body temp 

3. Increases effect of other depressant drug