Maureen Kanzler

Abuse potential of loperamide

Effects of the currently marketed form of loperamide (Imodium capsules) that might relate to abuse potential were examined. Study I was a double‐blind “dose run‐up” in adult male subjects with a history of illicit drug use but no history of opioid addiction. Subjective responses to doses of loperamide ranging from 12 to 60 mg were compared with responses to 120 mg codeine sulfate (96 mg base) and to placebo. Based on study I, loperamide (60 mg) was used in study II and its effects were compared with those of codeine (96 mg base) and placebo in an exaddict subject group. Study II subjects had had extensive opioid experience but were not actively addicted at the time of this double‐blind, inpatient study. In study II, as in study I, unlike loperamide and placebo, codeine induced pupillary constriction. Loperamide (60 mg) induced a detectable subjective effect in somewhat over half the subjects, was “liked” little or not at all, and was identified as “dope” at a frequency less than that for a threshold dose of oral codeine. It was concluded that in its present form, i.e., capsules containing loperamide mixed with magnesium stearate, loperamide poses little threat of potential abuse.

Nicotine: Cotinine levels in blood during cessation of smoking * **

HE ROLE OF NICOTINE as a primary reinforcer and of nicotine withdrawal as a factor in maintaining cigarette smoking behavior has been recently reviewed by Jarvik. ~ In this paper, we present an exploration of the relationship between the amount of nicotine in cigarettes smoked per day, serum cotinine levels, and difficulty in modifying the smoking habit. Cotinine is the major nicotine metabolite. In contrast to the short half-life of nicotine itself, the half-life of cotinine in blood is far longer (30 hr versus 30 rain, respectively). Furthermore, cotinine is usually found in the blood at levels greater than that of nicotine, 2-s and cotinine levels remain fairly constant in individuals who smoke according to a consistent pattern. 2.4.r On this basis, we felt that serum levels of cotinine would be a better index of the degree of chronic nicotinism than measures of the parent alkaloid. Cotinine is approximately 50 times less toxic than nicotine in rats. s-lo In this study, participants in a smoking cessation program were asked to rate themselves in terms of the difficulty they experienced in giving up smoking. They also provided information on the number and type of cigarettes they had been smoking. We then examined the correlations between this information provided by the participants, their success in stopping cigarette use, and serum c0tinine levels taken at several points during the course of the participaIion in the cessation program. In addition, we attempted to ascertain activity of the sympathetic system by measuring plasma dopamine-beta-hydroxylase (DBH).

The Efficacy of Electroconvulsive Therapya

A criticism often raised about electroconvulsive therapy (ECT) is that it, like other somatic treatments in psychiatry, has no rational basis.’ We are ignorant of “how” and “why” ECT is so powerful as an antidepressant agent. In the case of ECT, however, this charge, in important respects, is wrong. Largely following the work of Ottosson: for a quarter century it has been accepted that the elicitation of a generalized seizure is essential to the therapeutic process. In depressed patients, chemical or electrical inductions of generalized seizure appear to be equivalent in producing strong therapeutic results.’-5 Using bilateral ECT, Ottosson reported that there was no difference in rates of therapeutic response when a traditional electrical dosage was compared to a more intense, supramaximal dosage.2 Blockade of the seizure discharge with an anticonvulsant medication or the use of subconvulsive electrical dosage is known to be nontherapeutic.2s68 On the basis of this evidence, the most widely accepted view has been that the elicitation of a generalized seizure provides both the necessary and sufficient conditions for the antidepressant properties of the Furthermore, there have been longstanding indications that electrical dosage and/or waveform characteristics are related to the cognitive side effects of ECT.2*”*’2 Configurations requiring greater electrical intensity are generally associated with more profound side effects.” d’Elia and colleagues recently summarized this view, stating: “An optimal therapeutic effect depends on the Occurrence of a generalized, tonic-clonic seizure. . . . On the other hand, supraliminal stimulation does not enhance the therapeutic effect. The organic

Low nicotine cigarettes: cigarette consumption and breath carbon monoxide after one year

Subjects who took part in a 12‐wk study of switching behavior were observed during the subsequent year. Data were obtained for 96 smokers every 3 mo. A sample of smokers who, at 12 wk, had switched to a brand delivering less than half the nicotine of their baseline brand were offered continued monetary incentives to participate for an additional 6 mo (maintenance study). In the maintenance study, subjects continued to smoke low‐nicotine cigarettes during the 6‐mo period in which money and contact reinforcement were continued; maintenance control subjects increased their tar and nicotine exposure significantly. In the follow‐up study of those who had not changed by more than 50%, the original control group, nonswitchers, and moderate switchers did not significantly change their nicotine exposure from what it had been at the end of the initial 12‐wk study. Carbon monoxide (CO) in breath showed remarkably little change across the year despite substantial changes in tar and nicotine exposure. To the extent that CO is involved in smoking‐related disorders, switchers derived little if any benefit from switching to low‐nicotine brands.

Acute Effects of Alcohol on Defensive and Primary-Process Language. Results with Three Human Volunteers

Alcohol was found to attenuate defensive aspects of speech. Contrary to expectations, primary-process language was shown to decrease by alcohol. These findings are congruent with previous studies which suggested alcohol not to activate specific moods consistently as measured by verbal behavior.