Short-term treatment with citicoline (CDP-choline) attenuates some measures of craving in cocaine-dependent subjects: a preliminary report.

The administration of cytidine-5'-diphosphate choline (CDP-choline, citicoline) to animals increases the rate of membrane phospholipid synthesis and elevates brain dopamine levels. Because cocaine dependence has been associated with increases in brain phospholipid precursors, as well as depletion of dopamine within the central nervous system, the present outpatient study was conducted to assess the safety of citicoline (500 mg bid) and to determine if short-term treatment alters mood states and cocaine craving in subjects with a history of cocaine dependence. In addition, measures of drug craving and mood states after presentation of cocaine-related cues were collected on two occasions: before and after 14 days of double-blind treatment with either citicoline or placebo. Subjects did not experience any side effects and citicoline treatment was associated with decreases in self-reported mood states associated with cocaine craving. These preliminary data are encouraging and suggest that citicoline warrants further study as a promising potential treatment for cocaine abuse and dependence that is devoid of side effects.

Sex differences in plasma cocaine levels and subjective effects after acute cocaine administration in human volunteers.

Gender differences after acute cocaine administration have received little attention in spite of the fact that males and females respond differently to many drugs. Seven male and seven female occasional cocaine users received both an intranasal dose of cocaine hydrochloride (0.9 mg/kg) and placebo powder in a randomized order and reported subjective effects via an instrumental joystick device and various questionnaires. Blood samples were withdrawn at 5-min intervals to assess pharmacokinetic differences. Male subjects achieved the highest peak plasma cocaine levels (144.4 +/- 17.5 ng/ml), detected cocaine effects significantly faster than females and also experienced a greater number of episodes of intense good and bad effects. Women studied during the follicular phase of their menstrual cycle had peak plasma cocaine levels of 73.2 +/- 9.9 ng/ml, which was significantly higher than when they were studied during their luteal phase (54.7 +/- 8.7 ng/ml), but there were no differences in their subjective reports of cocaine effects. In spite of the different cocaine blood levels and subjective effects, peak heart rate increases did not differ between males and females suggesting that women may be more sensitive than males to the cardiovascular effects of cocaine. These data suggest that there are significant gender and menstrual cycle differences in the response to acute intranasal cocaine administration and these differences may have implications for the differential abuse of this drug.

Mecamylamine blockade of both positive and negative effects of IV nicotine in human volunteers.

The ganglionic blocker mecamylamine blocks the positive reinforcing effects of IV nicotine, but has been shown to increase cigarette smoking behavior under some conditions. The effects of mecamylamine on subjective and physiologic responses to IV nicotine were evaluated in seven healthy male volunteer cigarette smokers who provided informed consent and resided on a clinical pharmacology research unit. On four separate days, each subject was given a different oral dose of mecamylamine (placebo, 5, 10, or 20 mg). One hour later subjects received the first of four doses of IV nicotine (placebo, 0.75, 1.5, and 3.0 mg); the remaining injections were given at 1-h intervals. Both the positive effects following 0.75 mg and negative effects following 3.0 mg of nicotine were significantly reversed by mecamylamine. Thus, the mecamylamine-induced increase in smoking may be due both to competitive blockade of nicotinic receptors and nicotine's reversal of aversive effects.

The impact of familial alcoholism on alcohol reactivity in female social drinkers.

Some individuals may have an inherent reactivity to alcohol that facilitates early development of characteristics associated with alcoholism. Although response to alcohol cues has been used to assess this reactivity, few studies have included women or investigated familial alcoholism as a variable. In this study, 23 female college students were divided into groups according to family history of alcoholism (positive or negative). Alcohol reactivity was measured by salivation, skin temperature, heart rate, mood state, and craving for alcohol following presentation of alcohol-related and neutral cues. Results indicate no correlation between salivary reactivity and alcohol craving, which suggests that these variables tap into different domains of cue reactivity. Findings demonstrate that alcohol cue reactivity can be assessed in female social drinkers and that familial alcoholism may influence salivary reactivity to alcohol-related cues.

Alcohol expectancies: effects of gender, age, and family history of alcoholism.

To explore the effects of gender, age, and positive (FH+) and negative (FH-) family history of alcoholism on alcohol-related expectancies, the Alcohol Expectancy Questionnaire (AEQ) was administered to 627 college students (female n = 430). In an attempt to control for consumption effects, only individuals who described themselves as heavy drinkers were included in the study. A 2 (Family History) x 2 (Gender) x 2 (Age Range) multivariate analysis of variance (MANOVA) was conducted on the six scales of the AEQ. Results indicated that FH+ females under the age of 20 years reported stronger expectancies of social and physical pleasure than did FH- females. Results also suggested that females over the age of 20 reported significantly lower expectancies of global, positive effects compared to all other subjects, regardless of family history of alcoholism. Finally, both male and female subjects under the age of 20 reported greater expectancies of global, positive effects, sexual enhancement, feelings of increased power and aggression, and social assertion compared to individuals over the age of 20. These results indicate that alcohol-related expectancies vary as a function of age, gender, and family history of alcoholism.