Cocaine: Short-term observations of users (1970-1983)

A number of studies have provided observations of contemporary patterns of cocaine use in the period 1970 to 1983. These studies have concentrated on selected populations of users that were seen at only a single point of time during this period. When reviewed chronologically, these observations suggest that patterns of cocaine use were changing rapidly throughout the period 1970 to 1983 and in particular for long-term users. For individuals engaged in continued use this change was characterized by increased dosage and frequency of use resulting in decreasing positive effects and increasing negative reactions including physical and psychological dysfunction. This changing pattern is also examined () in a series of longitudinal observations made on a sample of users studied at multiple points of time during this sane period. Users entered the 1970s with attitudes that supported their beliefs that cocaine was a “safe recreational drug.” Gay and Inaba () suggested that the rediscovery of cocaine in the 1970s was inevitable because its effect of euphoria and stimulation “reinforces and boosts what we recognize as the highest aspirations of American initiative, energy, frenetic achievement, and ebullient optimism” (). Phillips Read more […]

Cocaine: Longitudinal study of users (1975-1983)

Methods A total of 118 cocaine users were recruited for study in 1974. Of these, 19 were selected for interview and questionnaire study while 99 (85 males, 14 females) were selected for a more comprehensive longitudinal study. All 99 users (18-38 years old) were social-recreational users who met the initial requirement of having used a minimum of 1 gram of cocaine per month for 12 months (range 1-4 grams). The majority of users were students (73 percent,) while others listed their occupations as housewives, business people, writers, attorneys, physicians, secretaries, teachers, or unemployed. Exaninations and tests were performed on each subject at 6-month intervals for 4 years (1975, 1976, 1977, 1978) and then at approximately 18-month intervals for another 5 years. Examination procedures included a personal history questionnaire, drug history questionnaire, subjective drug effects questionnaire, mental status exanination, the Minnesota Multiphasic Personality Inventory (MMPI), the Experiential World Inventory (EWI), in-depth interviews, and physical examinations (for most subjects). In addition, assays were performed on samples of cocaine used by these subjects. An important caveat is that a number of users dropped 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 […]

Treatment of Nicotine Dependence

There are an increasing number of options available for the treatment of nicotine dependence. As noted above, nicotine dependence is a chronic, relapsing disorder, and treatment should be approached from this perspective. The U. S. Public Health Service’s Clinical Practice Guideline on Treating Tobacco Use and Dependence is a comprehensive review of smoking cessation research, with recommendations based on numerous meta-analyses. It is the best resource for evaluating currently available treatments, and therefore it is the basis for most of the conclusions that we present here. Pharmacotherapies To date, there are seven FDA-approved medications that reliably increase long-term abstinence rates. These includefive nicotine replacement therapies (NRT) (gum, transdermal patch, inhaler, nasal spray, and lozenge), and two non- nicotine medications (bupropion SR, and varenicline). NRTs are designed to wean smokers gradually off nicotine in a manner that reduces the severity of withdrawal symptoms and cravings to smoke. They are typically used during the first 8–12 weeks of tobacco abstinence. Although the products vary in their routes of nicotine delivery (with the patch providing the most consistent delivery and stable Read more […]

Treatment of Alcohol Use Disorders

In general, treatment for substance dependence involves a combination of several psychosocial interventions, which can be combined with pharmacological interventions. Treatment of AUDs can be preceded by a detoxification, depending on severity of alcohol dependence. Personality and Substance Misuse and Pharmacotherapy of Addiction are discussed in depth in site. A short description and discussion of psychological and pharmacological interventions in AUDs are presented below. Detoxification: Symptoms, Medication The first stage of treatment for alcohol dependence often consists of alcohol detoxification, in order to prevent complications during detoxification, and to diminish symptoms and adverse effects associated with detoxification. Symptoms can develop within several hours after last alcohol use, and usually show a peak 24–36 h after abstinence. Symptoms that can be experienced during alcohol detoxification are anxiety, restlessness, sleeplessness, sweating, nausea, vomiting, tremors, heightened blood pressure, and an increased heart rate. Alcohol detoxification is estimated to take a week, although sleep disturbances and psychological withdrawal symptoms can persist much longer. Monitoring of alcohol-dependent 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 […]

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 […]

Clinical Studies of Reproductive System Dysfunctions in Alcoholic Women

Alcoholic women may have several disorders of menstrual cycle function, including amenorrhea, luteal phase dysfunction, anovulation, and, in some instances, early menopause. Most available information about alcohol effects on reproductive function has been derived from clinical studies of alcoholic women during sobriety. Evidence of menstrual cycle dysfunctions is based on clinical history information and endocrine evaluations at the time of admission for treatment of alcohol-related medical problems. Disorders such as liver disease and pancreatitis, often complicated by malnutrition or other infectious disorders, are observed clinically. Since these medical disorders can also contribute to reproductive system dysfunctions, it is not possible to attribute abnormal menstrual cycles to alcohol alone. However, recent replications of these reproductive disorders in animal models under controlled conditions and in healthy social drinkers increase confidence in the validity of the clinical observations. Amenorrhea Amenorrhea refers to the complete cessation of menses. Amenorrhea has been consistently reported by alcoholic women, and this condition may persist for several months or for many years. Data from two clinical Read more […]