The myth of "the average alcohol response"

The human alcohol response literature often states or implies that there is little variation among normal individuals in their responses to a standard dose. To test this assumption, a wide variety of alcohol responses was reviewed in studies where the original, individual responses were available. All such responses showed variability among individuals. Seven alcohol responses (individual changes from pre-alcohol baseline in heart rate, systolic and diastolic blood pressure, automobile driving ability, and three tests for intoxication) in normal males are analyzed in detail. Each response shows marked, significant individual variability. Genetic differences among individuals (in addition to environmental differences) are probably important in producing this variability. Since normal persons can vary greatly in their alcohol responses, it is not only incomplete but misleading to give only the mean value. Information on the range and frequency distribution of responses is also needed.     

GABAA receptor subtypes: the "one glass of wine" receptors.

This review discusses evidence for and apparent controversy about, gamma-aminobutyric acid type A (GABAA) receptor (GABAAR) subtypes that mediate alcohol effects experienced during social drinking. GABAARs that contain the beta3 and delta subunits were shown to be enhanced by alcohol concentrations that mirror the concentration dependence of alcohol responses in humans. A mutation (alpha6R100Q) previously found in alcohol nontolerant rats in the cerebellar GABAAR alpha6 subunit is sufficient for increased alcohol-induced ataxia in rats homozygous for this mutation (alpha6-100QQ) and further increases alcohol sensitivity of tonic GABA currents (mediated by alpha6betadelta receptors) in cerebellar granule cells of alpha6-100QQ rats and in recombinant alpha6R100Qbeta3delta receptors. This provided the first direct evidence that these types of receptors mediate behavioral effects of ethanol. Furthermore, the behavioral alcohol antagonist Ro15-4513 specifically reverses ethanol enhancement on alpha4/6beta3delta receptors. Unexpectedly, native and recombinant alpha4/6beta3delta receptors bind the behavioral alcohol antagonist Ro15-4513 with high affinity and this binding is competitive with EtOH, suggesting a specific and mutually exclusive (competitive) ethanol/Ro15-4513 site, which explains the puzzling activity of Ro15-4513 as a behavioral alcohol antagonist. Our conclusion from these findings is that alcohol/Ro15-4513-sensitive GABAAR subtypes are important alcohol targets and that alcohol at relevant concentrations is more specific than previously thought. In this review, we discuss technical difficulties in expressing recombinant delta subunit-containing receptors in oocytes and mammalian cells that may have contributed to negative results and confusion. Not only because we have reproduced detailed positive results numerous times, and we and many others have built extensively on basic findings, but also because we explain and combine many previously puzzling results into a coherent and highly plausible paradigm on how alcohol exerts an important part of its action in the brain, we are confident about our findings and conclusions. However, many important open questions remain to be answered.     

On the potential health effects of consuming "non-alcoholic" or "de-alcoholized" beverages

This paper reviews the potential health risks for persons who consume the newly available "non-alcoholic" or "de-alcoholized" beverages which may contain trace amounts of ethanol (less than 0.5% by volume). The discussion includes relative risk rates for chemical dependency, fetal alcohol syndrome, chemical and natural hypersensitivity, cancer, cardiomyopathy, hypertension and cirrhosis for those who drink standard alcoholic drinks and "non-alcoholic" drinks. It is concluded that non-alcoholic drinks pose little risk for developing alcohol related problems based on our current physiological and psychocultural knowledge.     

Effect of dexfenfluramine on alcohol intake in alcohol-preferring "P" rats.

The intake of alcohol, in 2-h daily sessions, by the preferring (P) line of rats was reduced in a dose-related manner by acute subcutaneous (SC) administration of dexfenfluramine (DFEN). Ad lib intake of alcohol was reduced by chronic SC administration of DFEN. The effective doses and magnitude of effects of DFEN on alcohol intake are comparable to those previously reported for DFEN anorexia. Because DFEN anorexia is related to increased brain serotonin (5HT) activity, its effect on alcohol consumption may also be via 5HT.     

The Nebraska "Network of Drug-Free Youth" Program

ABSTRACT: This paper describes Nebraska's six-year experience with a successful prevention program to form and maintain local drug-free youth groups. More than 4,500 youth were involved at the time of a six-year evaluation survey. Nearly 91% of group members who responded reported being alcohol-free in the previous 30 days and almost all (97%) reported being tobacco-free. Thirty-eight percent of members met one or more of the federal criteria for "high-risk" youth. Sixty-eight percent of responding high-risk youth who previously used alcohol credited group membership with helping them quit or reduce use. The program appears to assist in delaying onset of alcohol, tobacco, and other drug use for youth in the program, and to assist in decreasing or eliminating use of alcohol and tobacco by adolescents who used before participating.     

Alcohol levels in Chinese lactating mothers after consumption of alcoholic diet during postpartum "doing-the-month" ritual.

This study examined the effects of exposure to ethanol through cultural practices by lactating mothers. Specifically, the pharmacokinetics of alcohol in Chinese lactating mothers was investigated after they consumed chicken soup flavored with sesame oil and rice wine (CSSR), a typically prescribed diet during the postpartum "doing-the-month" period. Experimental findings were employed to estimate the potential ethanol dose to neonates and determine associated health risks. Twenty-three lactating mothers were examined. Informed consent was obtained from each subject. The target alcohol dosage was 0.3g/kg. Milk and blood samples were collected at fixed time intervals from each subject following exposure to CSSR, and alcohol levels were determined. Acute health risks to infants were estimated by comparing the potential infant dosage to an established criterion dose. Blood alcohol level peaked at 20 min after exposure to CSSR and decreased almost linearly thereafter. Alcohol in milk reached a plateau roughly at 20-40 min after exposure to CSSR and then decreased. Alcohol pharmacokinetics among subjects varied widely. The coefficients of variation in subject alcohol concentrations were 16.5-46.2% (mean, 30.0%) for blood and 32.8-57.6% (mean, 44.4%) for milk. Mean maximal alcohol concentration in blood (30.2+/-5.0 mg/dl) was achieved at 23.5+/-7.6 min and in milk (31.6+/-10.3 mg/dl) at 31.7+/-12.7 min. Potential infant doses were 3.0-58.8 mg (mean, 13.4 mg), and the predicted time required for milk alcohol level to return to zero level was 175 min. The acute health risks for infants exposed to alcohol through their mothers' milk under the current exposure scenario are low (hazard index<0.2). Nursing infants at least 3h after ingesting a diet containing alcohol would further reduce potential health risks.     

Anatomical "circuitry" in the brain mediating alcohol drinking revealed by THP-reactive sites in the limbic system

The involvement of aldehyde adducts in the etiology of alcoholism continues to be supported by a number of experimental findings. These metabolites are synthesized endogenously from a condensation reaction of a biogenic aldehyde with a catechol- or indole-amine and act in the brain to augment or suppress the drinking of ethyl alcohol. When given by the intracerebroventricular route in an animal which does not prefer alcohol, certain tetrahydro-isoquinolines and beta-carbolines can augment significantly the voluntary intake of alcohol even in aversive concentrations. This paper describes the historical background and current status of the "Multiple Metabolite" theory of alcoholism. The recent identification of anatomical structures in the limbic-midbrain, limbic-forebrain of the Sprague-Dawley rat, which mediate changes in the intake of alcohol induced by tetrahydropapaveroline (THP) is also described. When injected in a low dose of 25 ng in a specific site, over a 3-day period, THP induces persistent increases in the intake of alcohol even in aversive concentrations. These THP-reactive sites comprise the substantia nigra, reticular formation, medial lemniscus, zona incerta, medial forebrain bundle, nucleus accumbens, olfactory tubercle, lateral septal nucleus, preoptic area, stria terminalis, and rostral hippocampus. A higher dose of 250 ng THP microinjected at homologous loci tends to inhibit the rat's self-selection of alcohol or exert no effect on drinking. Morphological mapping of histologically identified sites sensitive to THP revealed a distinct "circuitry" of neuronal structures overlapping both dopaminergic and enkephalinergic pathways. This "circuit" extends from the tegmental-nigral area of the midbrain rostrally to structures within the limbic-forebrain. When a THP-reactive structure, the N. accumbens, was lesioned by either of two neurotoxins, 6-hydroxydopamine or 5.7-dihydroxytryptamine, the rats' preference for alcohol increased sharply. This suggests that impairment of transmitter release, denervation supersensitivity or other perturbation of receptor function within this and other structures play a part in the aberrant drinking of alcohol. It is envisaged that a dopamine-enkephalin link underlies the mechanism for the onset, maintenance and permanency of alcohol preference generated by an aldehyde adduct. Finally, the "Two-Channel, Brain Metabolite" theory of alcoholism proposes that the transitory presence of an endogenously formed aldehyde adduct within cells of the brain causes a permanent perturbation of normal receptor processes and transmitter activity within synapses of specific structures of the limbic system. This theory thus explains the nature of the rewarding properties of alcohol as well as its complex addictive liability which is physiologically irreversible.     

Reducing drinking and related harms in college: evaluation of the "A Matter of Degree" program

OBJECTIVES: To examine the effects of a multisite environmental prevention initiative, the "A Matter of Degree" (AMOD) program, on student heavy alcohol consumption and resultant harms at ten colleges. METHODS: A quasi-experimental longitudinal analysis of alcohol consumption and harms was employed, using repeated cross-sectional survey data from the Harvard School of Public Health College Alcohol Study (CAS). Areas examined included seven measures of alcohol consumption, thirteen measures of alcohol-related harms, and eight measures of secondhand effects of alcohol use by others. Comparisons were conducted on self-reported behavior of students for the ten AMOD sites in aggregate and by level of program implementation, with students at 32 comparison colleges in the CAS, for each outcome. RESULTS: No statistically significant change was found in the overall ten-school AMOD program for outcome measures of interest from baseline (1997) to follow-up (2001). However, there was variation in the degree of environmental program development within AMOD during the intervention period. A pattern of statistically significant decreases in alcohol consumption, alcohol-related harms, and secondhand effects was observed, reflecting minor to more substantial changes across measures among students at the five program colleges that most closely implemented the AMOD model of environmental change. No similar pattern was observed for the low implementation sites or at 32 comparison colleges. CONCLUSIONS: While there was no change in the ten AMOD schools in study measures, significant although small improvements in alcohol consumption and related harms at colleges were observed among students at the five AMOD sites that most closely implemented the environmental model. Fidelity to a program model conceptualized around changing alcohol-related policies, marketing, and promotions may reduce college student alcohol consumption and related harms. Further research is needed over the full course of the AMOD program to identify critical intervention components and elucidate pathways by which effects are realized.     

"It wasn't me, it was them!" social influence in risky behavior by adolescents

Many years of concerted policy effort in Western countries has not prevented young people from experimenting with cigarettes, alcohol and marijuana. One potential explanation is that social interactions make consumption "sticky". We use detailed panel data from the Add Health survey to examine risky behavior (the consumption of tobacco, alcohol and marijuana) by American adolescents. We find that, even controlling for school fixed effects, these behaviors are correlated with lagged peer group behavior. Peer group effects are strongest for alcohol use, and young males are more influential than young females. Last, we present some evidence of non-linearities in social interactions.     

"Above the influence": how college students communicate about the healthy deviance of alcohol abstinence

Consumption of alcohol is widespread in U.S. culture, particularly among college students. Using a communication privacy management framework ( Petronio, 2002 ), this study examined how college students who abstain from alcohol negotiate communication of their nondrinking status and establish meaning in a culture in which drinking is the norm. Through 25 face-to-face interviews, this article explores the experiences of "healthy deviants"-individuals who engage in healthy behavior that violates traditional norms. Interviews identified that participants relied on privacy rules when determining whether and how to disclose their nondrinking status. If participants perceived more costs from the disclosure than rewards, they did not disclose. Participants enacted specific strategies to manage (non)disclosure of their abstinence from alcohol, providing practical ways for people who engage in healthy deviance to avoid or manage stigma.     

Removing the "magic" from drugs.

Following training courses, young people in Sri Lanka are demonstrating that the subjective influence of alcohol and other drugs, and the behaviour they allegedly induce, can be changed by undermining widely held beliefs on their effects. Support is thus emerging for the view that the "magic" or pleasurable experiences commonly ascribed to drugs have little to do with their chemical action.     

"Pssst . . . the really useful guide to alcohol": evaluation of an alcohol education television series

The paper reports on the effectiveness of a six-part television series ("Pssst . . . the really useful guide to alcohol") in changing viewers' knowledge and alcohol-related behaviours and attitudes. Comparisons between viewers and matched controls indicated significant increases in knowledge relating to alcohol. No changes in attitudes were found, although some behavioural change was indicated. These results are discussed in the context of wider-ranging alcohol-related health promotion initiatives.     

Cigarette Smoking as a Predictor of Alcohol and Other Drug Use by Children and Adolescents: Evidence of the "Gateway Drug Effect"

ABSTRACT: Data from a statewide survey, conducted by the Indiana Prevention Resource Center, of 20,629 Indiana students in grades 5–12 were analyzed to determine the extent to which cigarette smoking predicted use of alcohol and other drugs and acted as a so-called "gateway drug." A three-stage purposive/quota cluster sampling strategy yielded a representative sample of Indiana students, stratified by grade. Cross-tabulated data revealed a strong, dose-dependent relationship between smoking behavior and binge drinking, as well as use of alcohol and illicit drugs. Daily pack-a-day smokers were three times more likely to drink alcohol, seven times more likely to use smokeless tobacco, and 10–30 times more likely to use illicit drugs than nonsmokers. A stepwise multiple regression analyzed the role that the student's perceptions of the risk of using drugs and of peer approval/disapproval of the student's drug use, gender, grade in school, and ethnic background played in predicting alcohol and other drug use.     

The protective influence of spirituality and "Health-as-a-Value" against monthly substance use among adolescents varying in risk.

PURPOSE: To investigate the influence of two potentially protective factors, Health-as-a-Value and spirituality, on monthly alcohol, cigarette, and marijuana use in two multiethnic groups of adolescents varying in risk. METHODS: Three-hundred-eighty-two students from continuation/alternative high school, a population considered at risk for drug use, participated in the study. The other sample of 260 students was drawn from a medical magnet high school, and is considered to be at lower risk. Similar surveys containing measures of spirituality, "Health-as-a-Value," and monthly substance use, were distributed. Logistic regression analyses were performed. RESULTS: The analyses revealed that spirituality was protective against monthly alcohol use and marijuana use in the lower risk sample. In the higher risk sample, spirituality was protective against all monthly use. "Health-as-a-Value" (HAV) was protective against monthly alcohol use in the low risk sample, and protective against all monthly use in the higher risk sample. Importantly, when both constructs were entered into the same model, spirituality and HAV were independently protective of all monthly use for the higher risk sample and of monthly alcohol use in the lower risk sample. CONCLUSIONS: These findings extend earlier work on protective factors. "Health-as-a-Value" and spirituality may be protective against substance use in environments with different levels of use. Future studies should explore these findings in longitudinal analyses.     

A six year longitudinal study of the occupational consequences of drinking over "safe limits" of alcohol.

Although much research has focused on the psychological, social, and economic consequences of heavy problem drinking, there has been far less attention paid to the consequences of "moderate" drinking. This study used a unique opportunity to carry out a six year follow up of a cohort of male and female white collar workers in whom there was baseline information on alcohol consumption and access to details on sickness absence, labour turnover, and promotion. It has provided evidence that even moderate alcohol consumption in the working population is associated with social costs for the employer and the employee, including substantial sickness absence, and lack of promotion in men, although the increase in labour turnover was not statistically significant. The longitudinal examination of consumption in this study suggests that early intervention in a drinking career may reduce alcohol consumption and consequently avoid years of morbidity and sickness absence, as well as having a favourable influence on performance and labour turnover.     

A six year longitudinal study of the occupational consequences of drinking over "safe limits" of alcohol.

Although much research has focused on the psychological, social, and economic consequences of heavy problem drinking, there has been far less attention paid to the consequences of "moderate" drinking. This study used a unique opportunity to carry out a six year follow up of a cohort of male and female white collar workers in whom there was baseline information on alcohol consumption and access to details on sickness absence, labour turnover, and promotion. It has provided evidence that even moderate alcohol consumption in the working population is associated with social costs for the employer and the employee, including substantial sickness absence, and lack of promotion in men, although the increase in labour turnover was not statistically significant. The longitudinal examination of consumption in this study suggests that early intervention in a drinking career may reduce alcohol consumption and consequently avoid years of morbidity and sickness absence, as well as having a favourable influence on performance and labour turnover.     

Predicting the potential for risky behavior among those "too young" to drink as the result of appealing advertising

A survey of 273 children in Washington state used a predrinking behavior index as a behavioral outcome to assess media effects on precursors to drinking among children for whom alcohol consumption is not yet occurring. It also examined age trends in relevant beliefs and behaviors. Perceptions of advertising desirability, the extent to which it seemed appealing, increased steadily from third to ninth grade, whereas identification with portrayals, the degree to which individuals wanted to emulate portrayals, leveled off after sixth grade. Expectancies, positive social benefits perceived to be associated with drinking alcohol, also increased with age, particularly between sixth and ninth grade. When demographics and grade level were controlled, desirability predicted identification, and both predicted expectancies, which is consistent with media decision-making theory. Expectancies correlated with alcohol predrinking behavior, and expectancies predicted risky behavior, with demographics and grade level controlled. Predrinking behavior and reported risky behavior were correlated. The results provide cross-sectional support for the view that beliefs and desires developing by third grade prime children for future decisions regarding substance use.     

"That feeling of not feeling": numbing the pain for substance-dependent African American women

Using ethnographic methodology, the author uncovered the meanings and expressions of recovery care for substance-dependent African American women residing in an inner-city transitional home for substance abuse. A convenience sample of 12 key and 18 general participants revealed emotional pain associated with negative life experiences, including overt and covert racism, primarily within society but also within their family networks; and physical, sexual, and emotional abuse from parents, siblings, and male relationships. The women described feelings of abandonment associated with the death of loved ones, particularly mothers. They had attempted to numb their emotional pain with alcohol and drugs. As they moved through treatment and recovery, they began to work through past and current painful life experiences without using alcohol and drugs.     

Effect of low alcohol dose on behavioral "despair" in rats neonatally treated with antidepressant drugs

Rat pups were treated with monoamine uptake inhibiting antidepressant drugs, desipramine, imipramine or nomifensine (5 mg/kg) during the second and third postnatal weeks, and their later behavioral "despair," measured by Porsolt's swim test, was examined. At the age of two months, the desipramine-treated rats showed lengthened immobility in the swim test, and thus probably increased behavioral "despair." They also responded to 1 g/kg alcohol by shortening the immobility to the level of control rats. Neonatal treatment with either imipramine or nomifensine did not affect the swim test behavior. The results suggest that a low, stimulatory dose of alcohol was able to reverse the lengthened immobility in the swim test of rats treated with desipramine during the early postnatal period.     

The driver's role in fatal two-car crashes: a paired "case-control" study.

This population-based study examines drivers' characteristics associated with driving errors that resulted in fatal motor vehicle crashes. Routinely collected data from the Fatal Accident Reporting System were used to assess whether a driver initiated the crash (case) or was passively involved (control) in 6,506 two-car collisions (81% of 7,993 eligible events). A paired comparison of cases and controls avoided confounding by environmental factors, exposure to traffic, and differences in case fatality. The strongest predictor of crash initiation is alcohol (odds ratio (OR) = 11.5; 95% confidence interval (CI) 9.57-13.9). Odds ratios are elevated even at the lowest blood alcohol concentration levels and increase dramatically as alcohol levels rise. Drivers aged 40-49 years are least likely to initiate crashes; odds ratios rise in a U-shaped manner to 3.35 in teenagers (95% CI 2.72-4.13) and to 22.1 in drivers over 80 years (95% CI 14.2-34.5). Other risk factors for initiating a fatal crash are the following: not wearing a seat belt (OR = 1.54; 95% CI 1.35-1.75), driving without a valid driver's license (OR = 2.16; 95% CI 1.72-2.73), and having had a crash within the last year (OR = 1.21; 95% CI 1.07-1.38). Driving errors leading to fatal crashes do not occur at random, but are associated with specific driver characteristics. The risk factors for crash initiation among crash-involved drivers are similar to risk factors for crash involvement found in other studies. These findings suggest that driving errors often explain high rates of crash involvement, invite further use of crash initiation in traffic injury research, and underscore the value of population-based registries for analytic epidemiology.