Posttraumatic Stress Disorder in World War II and Korean Combat Veterans with Alcohol Dependency

Our country was confronted with the problems of postcombat adjustment while the Vietnam conflict was still winding down. Concerns centered on the disruptive impact of returning drug-dependent veterans, the overall problems of readjustment, and assessment of public attitudes. As is the case with each major conflict, health-care-delivery systems were forced to assess and react to the aftermath of combat. This took place within the framework of the disciplines of program evaluation, quality assurance, and clinically applied research. Out of this has evolved a determined attempt to understand the interaction between combat and psychiatric disorders including alcoholism. This chapter demonstrates the existence of a posttraumatic stress syndrome compounded by alcoholism in World War II and Korean Conflict veterans. These comorbidities have resulted in chronic maladjustment over a prolonged period of time. Recommendations suggest early detection and triage of a posttraumatic syndrome and co-related substance use disorder in people who experience any catastrophic stressor. In 1971 top management at Coatesville Veterans Administration Medical Center committed itself to the development of an aggressive treatment network that Read more […]

Alcohol: Brain Evoked Potentials as Predictors of Risk

Sensory evoked potentials are capable of demonstrating brain sensory and cognitive function. These measures of brain activity can be used to demonstrate genetic influences in alcoholism. Auditory evoked potentials have been used successfully to demonstrate inherited differences in alcohol sensitivity. As in animal models, these inherited differences are limited to particular neuronal mechanisms and are not a general property of all neurons. The P300 wave, which is elicited in particular paradigms in which the subject is required to attend to specific stimuli, is smaller in subjects who are at high risk for alcoholism by virtue of having an alcoholic father. These subjects at risk for alcoholism show lower P300 amplitudes in paradigms in which they are given small doses of alcohol. P300 is also small in younger high-risk subjects who have never been exposed to alcohol. The evoked potential data are in general agreement with earlier electroencephalographic data that suggested the presence of electrophysiological abnormalities in the children of alcoholics. Sensory evoked potentials have been used extensively over the past decade to characterize abnormalities in brain function. This chapter describes their use in studies Read more […]

Toxicology of Antidepressant Drugs

As many pharmacodynamic effects carry over from animals to man, many toxic effects may also be predicted from observations made in animals. However, some important toxic effects are not predictable from animal studies (WHO, 1966) and this limitation may apply particularly to drugs acting on the central nervous system, such as the antidepressants. Nevertheless, the recognition of species differences and similarities in responses is considered as an important means of predicting toxic effects in man. In the following, some degree of correlation is attempted by the comparison, whenever feasible, between toxicity in laboratory animals and adverse effects described in man, particularly in cases of acute intoxication. However, due to the differing amount of data that was available on various drugs and the widely varying experimental conditions employed, such a comparison may not always prove to be reliable. The following review has been restricted to antidepressants in clinical use and, as far as evidence was available from the literature, concentrated on two main categories of antidepressants, the monoamine oxidase (MAO) inhibitors and the tricyclics. The lithium salts are considered in a separate chapter of this volume. Read more […]

Toxicology of Antidepressant Drugs: Tricyclic Antidepressants

Animal Toxicity General Toxicology The LD 50 values for a number of tricyclic antidepressants, when administered to mice and rats in single oral or parenteral doses, are listed in Table Acute LD50 valuesa of some tricyclic antidepressants. Acute poisoning by tricyclic antidepressants usually leads to symptoms of central excitation followed at the higher and lethal dose levels by central inhibition. The symptomatology includes muscular weakness, twitching, stupor, respiratory disorders, ataxia, and tonic-clonic convulsions. Table Acute LD50 valuesa of some tricyclic antidepressants Imipramine Doxepine Nortriptyline Viloxazine Maprotiline Mouse i.v. p.o. 35 666 15- 20 148-178 26 327 60 1000 31 660- 900 Rat i.v. p.o. 22 625 13- 19 346-460 22 502 60-77 2000 38- 52 760-1050 a The values given are for LD50, single administration, in mg/kg body weight It is evident from Table Acute LD50 valuesa of some tricyclic antidepressants or from the reports of Pluviage () and of Ueki et al. () that no major differences in the acute toxicity of tricyclic antidepressants are apparent. Information on animal studies relating to the tolerance of tricyclic antidepressants Read more […]

Human Dependence on Tobacco and Opioids: Common Factors

Recent years have seen increasing acceptance of the notion that tobacco is an addictive or dependence-producing substance, particularly as it is used in cigarette smoking. This idea is supported by the observations that tobacco serves as a reinforcer (i.e., it maintains behavior leading to its use) and that most people who smoke cigarettes would like to quit but cannot, even in the face of well documented health risks and economic sacrifices (Surgeon General’s Report 1979). The term “drug dependence” suggests that (1) the drug serves as a reinforcer, (2) behavior occurs which is maintained by the opportunity to take the drug, and/or (3) other reinforcers are sacrificed as a consequence of taking the drug (). Many cigarette smokers in some degree satisfy these criteria for drug dependence (). Since cigarette smoking has only recently been conceptualized as an instance of drug dependence, it should be useful to systematically compare cigarette smoking with another more thoroughly studied dependence process such as opioid dependence or narcotic addiction. At first blush, cigarette smoke and opioid drugs appear to produce vastly differing pharmacological and behavioral effects: large doses of opioids can produce Read more […]

Human Dependence on Tobacco and Opioids: Physiologic Dependence

Physiologic dependence is a factor of significance in opioid dependence and of suspected significance in cigarette smoking. There are three primary aspects of physiologic dependence. The first is important in the maintenance of opioid-taking behavior, in which the emergence of the withdrawal syndrome is correlated with increasingly intense craving scores (). Some analogous findings in animal studies are that the onset of the opioid withdrawal syndrome is correlated with increased rates of drug-taking behavior () and increases in the reinforcing efficacy of opioid drugs (). The second aspect of physiologic dependence to opioids is the increasing propensity of a person in withdrawal to become anxious and to emit aggressive and antisocial acts (). The third aspect of physiologic dependence is the phenomenon of protracted abstinence (), which, in the most rigorous use of the term, refers to physiologic withdrawal signs that are present for more than six months following the onset of opioid abstinence (). Protracted abstinence to opioids has also been well documented in animal studies (). With regard to cigarette smoking, it has been recently postulated that withdrawal phenomena occur and are similar in certain respects Read more […]

Drug effects on behavior maintained by food, electric-shock presentation and stimulus-shock termination

Although early experiments did not find differences in drug effects depending on the type of event, more recent studies have reported several instances in which the maintaining event appeared to influence the effects of several drugs on behavior. For example, morphine, methadone, and the narcotic antagonists naloxone and nalorphine decreased responding maintained under 5-minute fixed-interval food-presentation schedules at doses that increased responding comparably maintained by the presentation of an electric shock (). Under similar schedule conditions, both amphetamine () and cocaine () increased responding maintained by these two events. However, appropriate doses of pentobarbital, ethanol, and chlordiazepoxide increased responding maintained by food, while only decreasing responding under shock-presentation schedules (). These findings suggested that there were several conditions under which certain drugs appeared to affect similar performances maintained under comparable schedules in an event-dependent manner. Further, as shown in Figure Effects of chlordiazepoxide on different control rates of responding under S-minute fixed-interval schedules of food or shock presentation. The event pen was defected downward Read more […]

Effects of Alcohol Abuse on Reproductive Function in Women

 Alcohol abuse and alcoholism are associated with disorders of reproductive function in both men and women. Amenorrhea, anovulation, and luteal phase dysfunction may occur in alcohol-dependent women and alcohol abusers. Yet there has been relatively little research on the consequences of alcohol abuse for female reproductive function. Recent clinical and survey studies of alcohol effects on pituitary gonadotropins and gonadal steroid hormones in women are reviewed. Experimental studies of the acute and chronic effects of alcohol on the hypothalamic-pituitary-gonadal axis in normal women and in animal models are also described. Recent studies of the acute effects of alcohol on opioid antagonist and synthetic LHRH-stimulated pituitary gonadotropins are summarized. Possible mechanisms underlying alcohol-induced disruptions of menstrual cycle regularity are discussed. The adverse effects of alcohol on reproductive function in men are well documented. Impotence and diminished sexual interest are common clinical complaints among alcohol-dependent men. Testicular atrophy, low testosterone levels, and gynecomastia are often associated with chronic alcohol abuse (). There is now considerable evidence that alcohol inhibits Read more […]

Studies of Acute Alcohol Effects in Women and Animal Models

Alcohol Effects on Basal Hormone Levels Another approach to examination of alcohol’s toxic effects on reproductive function is to administer a single acute dose of alcohol to a normal healthy woman or experimental animal and measure the effects on pituitary and ovarian steroid hormones. Through a systematic manipulation of alcohol dose and changes in hormone levels, it should be possible to establish whether alcohol primarily disrupts hypothalamic, pituitary, or ovarian function. Surprisingly, studies of acute alcohol administration have shown that alcohol has minimal effects on basal hormone levels. Alcohol did not significantly suppress LH or estradiol in normal women or in female macaque monkeys. These data suggest that a single episode of intoxication is probably not sufficient to suppress normal basal hormone levels and that repeated episodes of intoxication are required to produce the hormonal correlates of amenorrhea, anovulation, and luteal phase dysfunction observed in clinical studies. One procedural difficulty affecting all investigations of acute alcohol effects on basal hormone levels is that studies have usually been conducted during the early follicular or luteal phase of the menstrual cycle, when basal Read more […]

Benzodiazepines in the Treatment of Alcoholism

This post comprises three sections that cover the main aspects of benzodiazepines and alcohol: (1) the basic pharmacology of benzodiazepines; (2) use of benzodiazepines in the treatment of withdrawal; and (3) the use of benzodiazepines in treating alcoholics. The basic studies suggest that a major site of action of alcohol may be the GABA/benzodiazepine receptor complex and that compensatory alterations in this complex may underly withdrawal. In the section on alcohol withdrawal, interactions between the GABA/benzodiazepine receptor complex, sympathetic nervous system, and hypothalamic-pituitary-adrenal axis are discussed. Use of benzodiazepines in the treatment of the alcohol withdrawal syndrome are reviewed, including the possibility that the benzodiazepines may prevent withdrawal-induced “kindling”. Lastly, we review indications for, and efficacy of, benzodiazepines in long-term treatment of patients with alcoholism. Benzodiazepines are not indicated for the treatment of alcoholism. Furthermore, they have very few indications in alcoholics and their dependency-producing potency has to be appreciated when they are used in patients with alcoholism. The benzodiazepines () are a group of compounds that were first Read more […]