Alcohol NHSDA 2000 Use Statistics (National Household Survey on Drug Abuse)

• “Drink” = can or bottle of beer, glass of wine or a wine cooler, shot of liquor, or mixed drink with liquor in it.

• Current use - At least one drink in the past 30 days (includes binge and heavy use).

• Binge use - Five or more drinks on the same occasion at least once in the 30 days prior to survey (includes heavy use).

• Heavy use - Five or more drinks on the same occasion at least five different days in the past 30 days.

Positive Effects of Moderate Doses (1-2 drinks/day)

• Pleasurable

• Anxiolytic (relieves anxiety and depression)

• Increases socialization (“the social lubricant”)

• Lowers mortality rate relative to non-drinkers

– probably due to elevating HDL (“good” cholesterol)

• Increases levels of estrogen (easing postmenopausal symptoms) Expectancies and Advertisement

• Many “positive” effects of alcohol are expectancy-based – Sociability – Attractiveness – Sexual prowess –Etc.

• Where do alcohol expectancies come from?

Negative Effects of High-level Consumption

• Reduced sex drive • Shrinking brain, enlarged ventricles • High blood pressure • of the liver • Peripheral Neuropathy • Korsakoff’s Syndrome •Depression • Decreased brain glucose metabolism Negative Effects continued

• Cerebellar degeneration • Increased risk of stroke • Muscle inflammation and atrophy • Men: testicular atrophy, decreased sperm and testosterone production, impotence • Women: menstrual irregularities • Addiction Acute Cognitive Impairments

White et al., 1998 • Memory formation • Attention (divided, selective) • Reaction time • Visual search and tracking • Abstract thinking • Problem solving/flexibility • Multi-tasking • “Alcohol myopia” • Impaired judgement of abilities • Flattened P300 Typical examples of P300

Normal Alcoholic

Karaaslan et al., 1999 Tapert et al., 2001

Non-drinkers Alcoholics

18-25 year olds performing a nonverbal working memory test Pharmacokinetics

• Both water soluble and lipid soluble • Absorbed through lining of digestive tract • Follows zero-order kinetics for elimination • 5-15% excreted unmetabolized through exhaled breath, sweat, urine • 85-95% metabolized in liver • build up of acetaldehyde leads to “flushing response”

Ethanol Acetaldehyde Acetate Alcohol Aldehyde Dehydrogenase Dehydrogenase Old Pharmacodynamic View

• Lipid Perturbation Hypothesis (Meyer, 1901) – Alcohol disturbs cell membrane integrity – Leaky cells allow chemicals in more easily – Widespread non-specific effects

• Alcohol does do this, but so do things like a slight change in temperature (i.e., fevers)

• More specific effects on receptors… Acute Pharmacodynamics

• Indirect agonist at GABAa receptor • Inverse agonist at NMDA receptor • Facilitates DA, 5-HT neurotransmission

• Increases DA levels in NAc, via some indirect GABAa effect

Ro15-4513, a GABAa antagonist (indirect for GABA, direct for alcohol) reverses Alcohol and Chronic Pharmacodynamics (adaptive processes)

• Decreased GABAa receptor function • Increased density of NMDA receptors

• Decreased DA function

• 5-HT dysfunction Tolerance

• Behavior – commonly half the level of behavioral intoxication at same blood alcohol level of nontolerant individuals – environment-dependent tolerance – learned tolerance

• Pharmacokinetic Mechanism – liver increases enzyme levels – accounts for up to 25% of tolerance

• Pharmacodynamic mechanisms

– changes in NMDA and GABAa receptors as per chronic effects Withdrawal

• Excitatory/inhibitory amino acid imbalance – Hyperexcitability – Seizures

• (DTs) - about 5% of patients develop it and a 35% mortality rate if untreated – Tremors – Hallucinations – Psychomotor agitation – Confusion – Disorientation – Sleep disorders • Dysfunctional monoamine systems –Depression Pharmacotherapies

• Benzodiazepines – For acute withdrawal

• (Antabuse) – Interferes with alcohol metabolism – Causes aversive reaction (like flushing response)

• Naltrexone – Opioid antagonist – Supposed to decrease craving – Efficacy still under debate Pharmacotherapies (cont.)

• Antidepressants – Causal direction between and depression unclear – May treat underlying motivation to drink, or reduce depression as withdrawal symptom Family History Positive

• FHP: one or more first-degree alcoholic relatives • 3-7x risk of alcoholism (esp. males) • Increased response to pleasurable (and reinforcing?) effects, decreased response to impairing effects – May map onto periods of increasing vs. decreasing blood alcohol level (BAL) • Decreased cortisol ( hormone) response • Smaller decrease in P300 amplitude from acute alcohol