Drugs and Behaviour: Ethanol Abuse and Dependence

Liquor

• Alcohol is fermented and distilled to produce a variety of products.

• Alcohol has a long history with humans and has influenced culture in many ways.

• Alcohol usually is measured in terms of blood alcohol concentration

• (BAC), and breathalyzers are effective ways to measure BAC.

• Alcohol acts on various neurotransmitters, including GABA and dopamine.

• Alcohol has significant impacts on the body and mind

  • These can range a great deal from disinhibition to memory loss.

• Alcohol in moderate amounts has some positive aspects on the body

  • Including lowering the risk for heart disease.

• Alcoholism has many negative aspects on the body

  • This can range from cirrhosis to strokes.

• Alcoholism can be treated with behavioral plans and with pharmacology.

Sources of Alcohol

Defining

• While there are many forms of alcohol, including methanol… we will be focusing on ethanol, the alcohol that is consumed. Defining alcohol

Fermentation

• is a process using yeast and sugar, usually grapes or grains. Fermentation

Distillation

• Is a process that includes heating fermented products. The vapor is cooled and is higher in alcohol.

• Distilled products include fortified wine, liquors, and spirits. Distillation

Origin and History

• Alcohol consumption dates back to ancient Chinese, Greeks, and Egyptians

• English known for ale, cider, and mead

• US history includes drinking houses, Prohibition, and increased consumption post-Prohibition

Measuring Ethanol Levels

Measuring Alcohol Levels

• The BAC is generally measured through a Breathalyzer, although it can also be measured with a blood sample.

• Alcohol vapor in the breath is equal to alcohol dissolved in the water of the blood at a partition coefficient of 2100:1.

• The literature usually refers to the alcohol concentration in the blood determined by Breathalyzer as BrAC.

Expressing BAC

• BAC is reported as milligrams (mg) of alcohol per 100 milliliters (ml) of whole blood.

• It may also be a percentage.

• For example, a BAC of 80 mg of alcohol per 100 ml of blood (or 80 mg / dl) is equivalent to 0.08%.

Using SI Units

• There has been a recent trend of reporting drug concentrations in SI units (Système International d'Unités).

• This measurement accounts for the molecular weight of the drug.

• The SI unit of concentration is millimoles (1/1000th molecular weight) of alcohol per liter of blood (expressed as mmol/L, 10-3 mol/L, or mM).

• For example, 80 mg of alcohol per 100 ml of blood is equivalent to 17.4 mM.

Pharmacokinetics

• How is alcohol absorbed?

  • Most alcohol is absorbed through the small intestine. Food helps slow the absorption of alcohol by keeping alcohol in the stomach longer.

  • Enzymes break down alcohol in the digestive tract, but the majority occurs in the liver. Some drugs, like Zantac, can increase BAC.

  • Women have less alcohol dehydrogenase in the stomach than men.

• Time to reach peak BAC

  • Variables such as food affect the time to reach peak BAC.

  • It generally takes about an hour to begin to reach peak BAC

  • The concentration of the drink also impacts BAC.

• Distribution

  • Alcohol is highly soluble in water, but not in fat, so a person's body composition affects distribution.

  • Women have higher fat composition, so they are more affected by alcohol than men.

• How is alcohol eliminated?

  • Between 90–98% of alcohol is processed by the liver.

  • So in theory, what should the time course be for alcohol in our system?

TIME COURSE

The time course for metabolizing alcohol

• There are several factors that affect the phases of alcohol metabolism, including weight, sex, and prior use of alcohol.

PHARMACOKINETICS

How is alcohol eliminated?

• Between 90–98% of alcohol is processed by the liver.

• Initially, alcohol is converted to acetaldehyde and then to acetate. Some of it may then turn into acetyl coenzyme A, which is used in several bodily processes.

  • Widmark, in the 1930s, reported that alcohol follows zero-order elimination kinetics, meaning that alcohol is removed from the body at a constant rate, but varies greatly between individuals.

  • More sophisticated technology shows that alcohol actually follows first-order elimination kinetics and is dose-dependent.

Rate of metabolism

• The rate that alcohol is metabolized depends on drinking experience, sex, and age.

• Genetic variation of alcohol-metabolizing enzymes (ADH and ALDH) also plays a role.

• Eating helps speed up alcohol metabolism.

PHARMACODYNAMICS

NEUROPHARMACOLOGY

• Alcohol interacts with different neurotransmitter systems to produce its effects!

• Alcohol concentration

  • Alcohol must be present in much higher doses than other drugs to create an effect.

• Principle neurotransmitter systems

  • While the precise mechanisms are still being uncovered, the primary systems appear to be GABA, glutamate, dopamine, and opioids, or reward centres.

GABA

• At the GABA receptors, alcohol enhances the inhibitory effects of GABA by increasing the frequency and duration of Cl– ion channel opening and decreasing the duration of channel closing.

• Detoxification takes days or weeks, and GABA receptors are impaired.

• GABA-A: ionotropic, inhibitory

• GABA-B: Metabotropic,inhibitory

Effects on the body

• Because GABA_A receptors are so widespread in the cortex, alcohol has strong impacts on behavior, emotion, and cognition.

• Inhibition of subcortical regions can account for changes in cognitive arousal, attention, memory, and mood.

Glutamate

• Glutamate maintains a balance between excitement and inhibition.

NMDA receptor

• Acts as a binding site for alcohol.

• With chronic alcohol use, the brain becomes more sensitive to glutamate as a means of compensating for prolonged depression by alcohol.

• Alcohol’s effects on glutamate and GABA combine to affect the CNS.

Endogenous Opioids

• Alcohol’s impacts on endogenous opioid receptors

• Alcohol consumption impacts the production and release of opioids and, as a consequence, activity of the dopamine systems with which they interact.

• It enhances drug liking (Notice this is still a running theme….).

Dopamine

• Alcohol increases dopamine activity and increases stimulation, euphoria, and drug wanting (Notice this is still a running theme….).

• However, with chronic alcohol consumption, there is a down regulation of dopamine (D2) receptors in the ventral striatum, which could represent a homeostatic mechanism to prevent overstimulation of the dopaminergic system.

EFFECTS ON BEHAVIOUR

Positive side effects

• Improvement in mood

• Reduction of stress

Severe Adverse effects of High BAC

• Disorientation

• Dulled senses

• Poor cognitive function

• Reversible drug-induced dementia

• Alcohol poisoning

Cultural impacts

• Language, including the many words of alcohol and inebriation, show the cultural impact of alcohol.

Defining wasted

• Studies show that inebriation initially results in people being more talkative, using a higher pitched voice, and being excited.

• As inebriation continues, people become more boisterous. This is followed by sleepiness and then nausea.

• Following nausea and vomiting, people become lethargic, enter a stupor, and may experience blackouts.

• Not everyone is impacted the same way, and lethal doses have been reported with BACs as low as 200 mg/100 ml.

Subjective Effects

• At low doses, most people report feeling stimulated, but at higher doses, sedation and anger occurs.

• People who report higher levels of stimulation also tend to report higher levels of liking.

Effects on Perception

• Alcohol is detrimental to vision, taste, and smell.

• People also have lower pain sensitivity when they drink alcohol.

Effects on Sleep

• For non-alcoholics, alcohol can decrease the time it takes to fall asleep and increase non-REM sleep, but only for the first half of the night.

• For chronic users, alcohol increases insomnia.

Effects on Memory

• While alcohol affects all aspects of memory, it most strongly affects storage.

• Alcohol decreases the effectiveness of working memory.

Blackout

• Drinkers often experience grayouts, where they can remember only parts of an event.

• En bloc blackouts occur when there is no memory of an event and nothing is stored.

Effects on Motor Performance

• Alcohol negatively affects reaction time and hand–eye coordination.

• Expectation plays a role in how alcohol will impact motor performance.

How does alcohol affect driving ability?

• Alcohol impacts most of the brain regions needed for driving, including the orbitofrontal cortex, motor areas, the anterior cingulate, and inferior frontal gyrus. The hippocampus is also impacted by alcohol.

• As BAC increases, the likelihood of being in a crash rapidly rises.

Disinhibition and Behavior Control

• The impact of alcohol on disinhibition

• Alcohol lowers inhibition and people are more likely to ignore social norms.

• Disinhibition is related to the societal expectation of how to act when using alcohol.

Systemic effects on the Body

• Alcohol dilates the capillaries and increases need to urinate.

EFFECTS OF ALCOHOL

• Protective effects of alcohol in low to moderate consumption

  • The effect that is given when substances that are dangerous at high levels but beneficial at low levels is called hormesis.

  • Wine was once given as medicine and brandy was called aqua vitae.

  • There is a U-shaped relationship between alcohol consumption and mortality. The plots are either U-shaped or J-shaped when looking at daily dose and relative risk for various health problems. For example, look at heart disease, diabetes, ischemic strokes.

  • The benefits of low and moderate use of alcohol appear to come from alleviating the effects of aging.

EFFECTS OF ALCOHOL: SHORT TERM HARM

• Immediate and short-term effects of acute alcohol consumption

  • As shown by Amy Winehouse, it is possible to die from alcohol.

  • A large number of people are admitted each year to the emergency room for alcohol poisoning.

  • Death by alcohol usually results from respiratory failure.

Hangover

• A hangover can be thought of as a form of mini-withdrawal.

• A little more alcohol the next day can help alleviate the withdrawal symptoms.

• Behaviors stemming from alcohol use

• Alcohol lowers inhibition and can contribute to negative behaviors that impact others.

EFFECTS OF ALCOHOL: CHRONIC ALCOHOLISM

• Studies reveal that chronic alcohol use is related to significant health disorders, ranging from reproduction to cancer.

  • Damage to the liver

    • Starting with steatosis, chronic alcohol use can then lead to cirrhosis.

    • Alcohol consumption leads to 50% of deaths from liver damage.

The Nervous System

• Damage to the nervous system

  • Heavy drinkers may show a loss of memory and ability to remember new things.

  • Korsakoff’s psychosis, or Wernicke–Korsakoff syndrome, results from a lack of thiamin.

  • From epilepsy to alcohol dementia, alcohol can have significant impacts on the nervous system.

Cancer

• Alcohol can have a genotoxic effect on the parts of the body exposed to alcohol.

• There is some evidence that alcohol can increase the risk for breast cancer among already at-risk populations.

Reproduction

• Among males, alcohol can cause impotence; Among females, it can disrupt menstruation.

• Alcohol use during pregnancy can result in fetal alcohol spectrum disorder (FASD), which includes fetal alcohol syndrome (FAS).

  • While the precise mechanism is unknown, animal studies have shown alcohol can disrupt neurogenesis, cell migration, cell adhesion, neuron survival, axon outgrowth, synapse formation, and neurotransmitter function in the developing brain.

Heart Disease

• Alcoholism can contribute to a condition in the heart similar to cirrhosis of the liver.

Other pathologies from alcohol use

• Chronic alcohol use can lead to many pathologies, including those from malnutrition.

ALCOHOLISM AS A DISEASE

• The DSM-5 recognizes alcohol dependence syndrome and alcohol use disorder as diagnostic diseases.

• Alcoholics Anonymous was a movement that effectively called attention to the disease.

Loss of Control

• The loss of control is the inability to limit drug intake and is measured by an escalation in drug intake with extended access.

• The effects of alcohol in the brain contribute to the high relapse rate of alcoholics.

• ALCOHOLISM AS A DISEASE

Reinstatement and priming

• Reinstatement is seen in social drinkers, while loss of control is found in alcoholics.

Tolerance

• Metabolic tolerance: increase in liver alcohol dehydrogenase enzymes and results in an increased rate of alcohol metabolism.

• Pharmacodynamic: reduced physiological responsiveness to alcohol’s pharmacological actions.

• Behavioural: reduced behavioral impairment to alcohol.

Withdrawal

• Occurs in 3 separate stages: early minor, moderate, and late major.

• The symptoms for late major syndrome can be severe.

Withdrawal

• Type I alcohol addiction

  • As occurring with those 25 and older and having low genetic risk but high psychosocial risk. Environmental variables such as stressful interpersonal situations or psychological disorders primarily account for type I alcohol addiction.

• Type II alcohol addiction

  • As occurring with those younger than 25 and exhibiting high genetic risk and traits associated with poor impulse control.

STAGE 1: Mild Symptoms

• WITHIN 6 TO 12 HOURS AFTER THE LAST DRINK.

• Symptoms involve changes in behavior and mood, and minor physical side effects.

• They mimic a hangover.

  • Unclear thinking

  • Headaches

  • Dilated pupils

  • Craving for alcohol

  • Nausea

  • Vomiting

  • Loss of appetite

  • Minor hand tremors

STAGE 2: Moderate Symptoms

• WITHIN 12 TO 48 HOURS AFTER THE LAST DRINK.

• Symptoms are more intense and create abnormal vital signs.

• Medical supervision is important. Seizures may begin during this stage.

  • Mental confusion

  • Hallucinations

  • Increased blood pressure

  • Irregular heartbeat

  • Breathing difficulties

  • Seizures

STAGE 3: Severe Symptoms

• WITHIN 48 TO 72 HOURS INTO THE DETOX PROCESS.

• Seizures and hallucinations can progress to "delirium tremens," a life-threatening condition.

  • Agitation

  • Disorientation

  • Hallucinations (mainly visual)

  • Rapid heartbeat

  • Excessive sweating

  • Fever

ALCOHOLISM AS A DISEASE

Genetics of Alcoholism

• Genetics appears to contribute to about half of the likelihood of heavy drinking.

Four characteristics

• These four characteristics are tied to genetics and can help predict a propensity to alcoholism.

• Polymorphism in genes that encode enzymes associated with the metabolism of alcohol (such as aldehyde dehydrogenase) constitute the most well-established genetic association with alcohol dependence.

FHP vs. FHN

• Family history positive or family history negative seems to have limited connection in predicting alcoholic behaviors.

• The exception appears to be with low-level sensitivity.

How do we treat alcoholism?

• There is no one-size-fits-all approach, but eliminating the physical dependency appears to be the first step.

• How a therapist views alcoholism affects the goals of the treatment.

Alcoholics Anonymous

• Founded in 1935, AA came from the Oxford Movement and focused on the aspect of fellowship to help overcome alcoholism.

• Every meeting includes the 12 steps and the 12 traditions of AA.

Pharmacotherapies for Alcoholism

• Only three substances have FDA approval for treating alcoholism. All work to lead to abstinence.

  • Acamprosate, disulfiram, and naltrexone are used to reduce alcoholic intake.

• Dopamine agents also appear to have some success.