Subjective Effects Of Alcohol Research Articles

Using Alcohol as a Standard to Assess the Degree of Impairment Induced by Sedative and Analgesic Drugs Used in Ambulatory Surgery

There is a need for a standard by which to compare the degree of subjective and behavioral impairment caused by anesthetic drugs, because anesthesiologists may not be able to gauge how extreme or important a statistically significant change in psychomotor functioning is. This study examined the psychomotor and subjective effects of alcohol at blood concentrations equal or greater than 0.10% as a standard with which to compare those effects caused by sedative and analgesic agents commonly used in ambulatory surgery. Twelve healthy human volunteers (11 men and 1 nonpregnant woman), with an average age of 28 yr (range 24-34 yr) and an average alcohol consumption of four drinks per week, were selected in this institutional review board-approved study. Each subject was exposed to five drug conditions (70 mg/70 kg propofol intravenously, 2 mg/70 kg midazolam intravenously, 50 micrograms/70 kg fentanyl intravenously, 0.8 g/kg alcohol orally, and placebo orally and intravenously) in a double-blind randomized fashion over five weekly sessions. Testing was done at baseline and at different intervals until 240 min after drug administration. Testing included psychomotor performance (Maddox Wing, eye-hand coordination, auditory reaction time test, and digit symbol substitution test), subjective effects (strength of drug effect scale, drug liking scale, and visual analog scale), and short-term memory. Psychomotor performance was used as an index of objective impairment, and mood was used as an index of subjective impairment. After consumption of the alcoholic beverage, a blood alcohol level of 0.11 +/- 0.003% (mean +/- SE) was obtained at 15 min after injection. The study drugs not only produced statistically significant impairment (i.e., impairment greater than that seen with placebo) but also, at one or more times after injection, produced impairment similar to that observed with alcohol at a blood alcohol concentration of 0.11%. Midazolam produced a similar degree of impairment to that of alcohol for a longer duration than did fentanyl and propofol. This study provides evidence that degree of impairment caused by sedative and analgesic drugs used in ambulatory surgery is similar to that obtained with a dose of alcohol that produces a blood alcohol concentration of 0.11%. We suggest that anesthesiologists can use alcohol as a standard by which to assess degree of impairment produced by drugs used for sedation/analgesia.

Effects of calcium channel inhibitors on ethanol effects and pharmacokinetics in healthy volunteers

Previous studies have shown that calcium channel antagonists alter the effects of alcohol in animals and humans. We selected a phenylalkylamine, verapamil, and a dihydropyridine, nimodipine, to determine whether these drugs would affect the subjective or psychomotor effects of ethanol in humans. Subjects ingested verapamil (80 mg, PO), nimodipine (30 and 60 mg, PO), or placebo 60 min before drinking an alcohol (0.7 g/kg) or placebo beverage. Subjects' mood, psychomotor performance, physiological status, and blood alcohol levels were assessed up to 3 h after beverage ingestion. Alcohol increased “drunk” ratings and impaired psychomotor performance ( p < 0.05). Blood alcohol levels were decreased by nimodipine pretreatment, but not by verapamil pretreatment. Subjective and psychomotor effects of alcohol were not altered as a function of nimodipine or verapamil pretreatment. Nimodipine, verapamil, and alcohol, either alone or in combination, had no effect on blood pressure or heart rate.

Alcohol‐induced reinforcement: Dopamine and 5‐HT3 receptor interactions in animals and humans

AbstractAlcohol abuse is a major health problem worldwide. Whatever the treatment goal, be it abstinence or “controlled” drinking, the outcome from both pharmacological and nonbiological treatments remains disappointing. Behavioural experiments in animals have suggested that the reinforcing properties of alcohol, like other drugs of abuse, are critical to drug‐seeking behaviour. Dopaminergic fibres running from the ventral tegmental area to the nucleus accumbens may play a central role in mediating the reinforcing effects of drugs of abuse including alcohol. Thus, alcohol increases extracellular levels of dopamine in the nucleus accumbens and dopamine receptor antagonists decrease alcohol consumption in a number of behavioural paradigms. A recently described subtype of serotonin (5‐HT) receptor, the 5‐HT3 receptor, appears to modulate the effects of alcohol on dopamine release in the nucleus accumbens. In rodents, 5‐HT3 receptor antagonists inhibit alcohol‐induced dopamine release in the nucleus accumbens. Further, in behavioural studies, 5‐HT3 receptor blockade decreases alcohol consumption in a free‐choice paradigm. In humans, reinforcement is difficult to measure directly. Nevertheless, the pleasurable subjective effects of alcohol are important behavioural correlates of the reinforcement process. Our preliminary findings in humans suggest that the 5‐HT3 receptor antagonist, ondansetron, can attenuate some of the pleasurable effects of a small dose of alcohol including the subjective desire to drink. We speculate, although we have no direct evidence for this at present, that in humans this effect could also be due to a blockade of alcohol‐induced dopamine release in the nucleus accumbens as has been demonstrated in animals. Further studies with clinical populations are required to assess the effects of 5‐HT3 receptor antagonists on drinking behaviour and to explore their potential in the management of alcohol abuse. © 1993 wiley‐Liss, Inc.

The Structure of the Expected and Actual Subjective Effects of Alcohol

The 23 items from Schuckit (1984) were administered to 156 medical students and an 11-item questionnaire was derived from a factor analysis of their responses. It measured six expectancy factors; (1) ability to perform after alcohol, (2) low mood, (3) arousal, (4) dizziness, (5) stomach symptoms and (6) heart symptoms. This was then administered to 90 male subjects who were going to receive alcohol in a balanced-placebo design. For these subjects, “Able to perform” was the largest prior expectancy factor and in ratings of actual current state after alcohol or placebo it was reduced by alcohol consumption. The other items combined to form a single factor “Side effects”, which, despite subjects expectations, was unaffected by alcohol consumption. It is suggested that intoxication is not unidimensional and that this brief questionnaire may be used to control for subject's expectancies.

Acute tolerance to alcohol: changes in subjective effects among social drinkers

The development of acute tolerance to the subjective effects of alcohol was examined in 32 social drinkers. Measures were made of self-reported level of intoxication and responses to questions from the alcohol scale of the Addiction Research Centre Inventory. The time to peak self-reported intoxication level was found to be 20 min earlier than the time to peak blood alcohol concentration. Changes from the ascending to the descending limb of the blood alcohol curve were found with five of the ARCI questions. In all cases the proportion of alcohol-typical responses was lower on the descending portion of the curve, even though blood alcohol levels were equivalent. Further analyses examined the effects of prior drinking history on the development of acute tolerance. Peak self-reported intoxication levels were significantly lower and occurred earlier for heavier drinkers. Furthermore, for four of the five ARCI questions heavier drinkers were less likely to give an alcohol-typical response than lighter drinkers on the ascending portion of the curve.

Carryover of tolerance to alcohol in moderate drinkers.

Details are given of the method and the results of a study which found that tolerance to the subjective effects of alcohol was increased by a simple previous drink, even when the blood alcohol concentration from the first dose has reached zero. Chronic tolerance and acute tolerance to alcohol are discussed and different mechanisms to account for these phenomena are proposed. The study results fit well with a functional description of drug effects. Heavy drinkers have been found to show more rapid adaptation than moderate drinkers. The study indicates the need to identify heavy drinkers who have a greater potential for developing alcoholism since they may adapt more rapidly than those without such potential. Those who adapt to alcohol extremely rapidly may be poorer candidates for moderation training than those who show more moderate adaptation. The study also shows that the internal monitor of intoxication is a heavily adapting system that cannot be relied on for an accurate assessment of blood alcohol content.

The interaction of alcohol and stress A review

The literature on the interaction of ethanol and stress is reviewed. Stress has amethystic properties in both experimental animals and human subjects when analgesia or various behavioral parameters were evaluated. In addition studies have shown that ethanol counteracts some effects of stress in non-alcoholic subjects. Improvement in performance and in the affective state of humans and reversal of some behavioral and pathological concomitants of stress in experimental animals have been reported. Although there is indication that ethanol improves the affective state in humans, reduction of anxiety has not been a universal finding. Recent studies have pointed out a number of variables (the drinking environment, cognitive set, mood and personality of subjects, prior experience with ethanol, sex, dose and type of beverage) which can significantly alter the effects of alcohol in human subjects. These may account for the variability in results in the literature. Although some studies have shown that alcohol ingestion increases under stressful conditions, others have failed to do so in both experimental animals and in humans. In alcoholics ethanol ingestion, in general, does not appear to relieve anxiety. In fact anxiety usually increases with time during a drinking binge. Therefore more research needs to be done to assess the validity of the anxiety-reducing theory for alcohol abuse. Possible mechanisms for the interaction of stress and alcohol are discussed.

A Comparative Look at Ratings of the Subjective Effects of Beverage Alcohol

The alcoholic’s drinking behavior is commonly accounted for by a tension reduction hypothesis (TRH). However, comparison of the phenomenological states experienced by “addicted” and nonaddicted” alcohol users suggests the existence of a strongly elevated alcohol-induced euphoria in addicted alcoholics which may contribute to the genesis and support of the characteristic alcoholic syndrome.

Acute hemodynamic effects of ethanol on normal human volunteers.

Abstract Data on the acute hemodynamic effects of alcohol in human subjects are conflicting. In the present study there was a significant increase in the cardiac output in the 10 young normal subjects 30 minutes after the ingestion of 6 oz. of 90 proof bourbon whiskey due to an increase in the heart rate without a change in stroke volume. The arterial pressure was unchanged. Left ventricular contractility ( dP dT ) was unimpaired. Alcohol had no effect on the hemodynamic response to a work load of 100 watts for 5 minutes. These findings conflict with previous observations on middle-aged chronic alcoholics. The variability noted in these earlier observations may be due partly to the effect of age itself but more probably and importantly to subclinical cardiomyopathy in chronic alcoholics.