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: 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 […]

Tricyclic Antidepressants: Intoxication in Man

Effects of Acute Overdose Most of the numerous publications on acute intoxication with tricyclic antidepressants deal with attempted suicide in adults or with accidental selfpoisoning in children. Taking into account the difficulty in establishing the dose ingested – particularly in the case of children and of successful suicides – it is not surprising that it is difficult to predict the severity of an acute intoxication from the dose apparently taken. In children, fatalities have occurred with doses below 500 mg and survival with doses as high as approximately 1,700 mg. In adults, doses below 1,000 mg may already prove fatal but survival has been reported with doses up to 4,000 mg or higher (). In children, the critical dose level for imipramine seems to lie around 500 mg. Of a survey comprising 34 cases, only two children who had ingested less died whereas only three with larger doses survived (). Adults, who have ingested 1,000 – 2,000 mg still have a good chance of recovery whereas the risk of a fatality becomes far greater at levels of over 2,000 mg (). In relation to body weight, an LD50 value for imipramine has been determined for children at 40 – 50 mg/kg and for adults at 30 – 50 mg/ kg (). The symptoms 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 […]

Drug Preference in Humans: Lorazepam

A drug’s capacity to reinforce behavior in a laboratory setting usually correlates with its dependence potential in the general population. In laboratory tests, diazepam is not an effective positive reinforcer, either in laboratory animals using drug self-administration tests () or in normal human volunteer subjects using a choice test (). The failure to find evidence for a positive reinforcing effect of diazepam in these experimental tests is inconsistent with clinical reports that diazepam is used excessively by some people. The failure to demonstrate the positive reinforcing efficacy of diazepam in an experimental situation may be due in part to the drug’s long duration of action (half-life = 24 – 48 hours). In animal self-administration studies that test the reinforcing efficacy of drugs, it has been found that benzodiazepines that have shorter durations of action are also more effective reinforcers (). In the present study, human subjects were tested for preference for lorazepam, a benzodiazepine with effects similar to diazepam but with a shorter half-life than diazepam (half-life = 12-15 hours). Method Subjects. Twelve normal healthy volunteers, aged 21 to 27 (4 males, 8 females) participated in this study. 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 […]

Benzodiazepines in the Treatment of Alcoholism: Future Directions

The above treatment recommendations emphasize that minimal signs and symptoms of ethanol withdrawal can generally be treated without pharmacotherapy. The repeated experience of untreated ethanol withdrawals, however, may produce a “kindling” effect over time. Kindling is the “progressive increase in neural responsivity produced by spaced and repeated epileptogenic stimulation of certain brain structures.” The kindling hypothesis suggests that each additional episode of withdrawal will elicit increasingly severe signs and symptoms. Preclinical studies in which the severity of the ethanol withdrawal syndrome increased in rats subjected to repeated episodes of ethanol withdrawal or following kindling induced by electroshock, metrazol injections, or amygdaloid stimulation indicate that such a process may take place. In addition, a retrospective study in alcoholics reported that periods of heavy drinking and dependence on ethanol were associated with an exacerbation of agoraphobia and social phobias, and that subsequent periods of abstinence were associated with substantial improvements in these phobic anxiety states. A recent study demonstrated that patients with panic disorder and alcohol dependence do not distinguish Read more […]

Benzodiazepine Treatment of the Ethanol Withdrawal Syndrome

The objective of drug treatment in ethanol withdrawal is the relief of subjective symptoms, the prevention or treatment of more serious complications such as seizures or delirium tremens, and the preparation for long-term rehabilitation with minimal hazard of new dependence problems or direct toxicity related to drug treatment. The ideal drug for alcohol withdrawal should have a rapid onset and long duration of action, wide margin of safety, metabolism not dependent on liver function, and absence of abuse potential. The various benzodiazepines offer many of these advantages; the selection of the most appropriate benzodiazepine will depend on the clinical situation. Withdrawal severity can be quickly and reliably determined upon admission by measuring breath alcohol concentration and administering an objective rating scale, such as the CIWA-A (Clinical Institute Withdrawal Assessment of Alcohol). Patients in mild ethanol withdrawal (CIWA-A<20) and without a prior history of withdrawal seizures can generally be treated conservatively (fluids, multivitamins, reassurance, antacids, thiamine). Treatment without medication offers the patient an opportunity to exercise nonpharmacological control over his or her life Read more […]

Drug Impairment Reviews: Opiates and Minor Tranquilizers

STUDY: Gordon, N.B. Reaction Times of Methadone-Treated Heroin Addicts. Psychopharmacologia, 16:337-344. 1970. Site: Rockefeller University and Yeshiva University, New York City, New York. Subjects: The subjects were divided into six groups. Groups 1 and 3 both had been maintained for at least 1 year on methadone for the treatment of heroin addiction. Group 1 had 18 males whose average age was 32.5 years; group 3 had 9 females whose average age was 33.5 years. Group 2 consisted of 20 unpaid male volunteers who did not use drugs; they averaged 32.5 years. The participants in groups 4 and 5 had recently withdrawn from narcotic drugs. The 20 males in group 4 averaged 31.5 years and had withdrawn 14 days earlier. The 19 males in group 5 averaged 30 years and had withdrawn 4 days earlier. Group 6 consisted of 9 females whose average age was 23 years. They were paid volunteers from the nonprofessional hospital staff, and did not use drugs. Method: Measurements were taken under controlled laboratory conditions; urines were tested (details were not given) for drugs to assure conformity to group. Variations of reaction time were tested in a button-pressing situation: (a) simple reaction time (one of six stimuli); (b) Read more […]

Drug Interaction on Psychomotor Skills Related to Driving: Diazepam and Alcohol

STUDY: Linnoila, M., and M.J. Mattila: Drug Interaction on Psychomotor Skills Related to Driving: Diazepam and Alcohol. Europ. J. Clin. Pharmacol., 5:186-194. 1973. Site: Department of Pharmacology, University of Helsinki, Helsinki, Finland. Subjects: The four hundred volunteers (371 males, 29 females) were comprised of medical students, technical students, and cadets. A brief history was taken to exclude subjects suffering from diseases or taking drugs. (Caffeine and tobacco were not specifically mentioned as being exclusionary, but coffee and “drugs” were stated as excluded “during the tests.”) The mean age of the subjects was 22 years (S.D. = 2.8 years). The subjects were divided into 20 groups of 20 subjects each which were similar in sex, age, weight, educational level, and district of residence. Driving experience was not mentioned. Results of only 10 of the test groups are reported in this article. Method: The research was experimental, under controlled laboratory conditions, using double-blind technique. Coding was changed daily, and 10 subjects were tested each day. Before any administration of drugs and drink, the subjects were instructed in the test procedures and apparatus by the same person in Read more […]