Progesterone treatment during the early follicular phase of the menstrual cycle: effects on smoking behavior in women.

The goals of this study were (1) to examine the feasibility of administering progesterone to women during the early follicular phase when the endogenous estradiol and progesterone levels are low, and (2) to investigate the effects of oral progesterone treatment on smoking behavior in female smokers. Twelve subjects had two experimental sessions, within 3-9 days after the beginning of their menses. In each experimental session, subjects received a single 200-mg dose of progesterone or placebo, orally. Two and a half hours after the medication treatment, subjects were assessed for subjective response to two puffs of a cigarette and then started the self-administration period in which they had the option to exchange their token for two puffs of cigarette, 15 min apart. Subjects had low levels of estradiol and progesterone before the first and second sessions. Plasma progesterone levels peaked in 2 h following progesterone treatment. Progesterone treatment attenuated the craving for and subjective effects from smoking. Under progesterone treatment, there was a trend for decreased smoking behavior. These preliminary results suggest that the early follicular phase of the menstrual cycle may be a useful interval to investigate the effects of exogenous progesterone in female smokers. The effects of progesterone on nicotine dependence need to be studied further.

Depressive symptoms modulate the subjective and physiological response to cocaine in humans.

The goal of this study was to examine the relationship between the presence of subclinical depressive symptoms and physiological and subjective responses to smoked cocaine in humans. Cocaine users without major depression, who participated in various inpatient studies, received a single 0.4 mg/kg of smoked cocaine. When the relationship between the Beck Depression Inventory (BDI) scores and various subjective and physiological responses to cocaine was examined, similar trends were found. Low BDI scores of 0-7 were associated with a smaller physiological and subjective cocaine response. In contrast, BDI ranges of 8-13 were associated with enhanced cocaine response which plateaued or declined in the higher (> 14) BDI group. These group differences were not explained by sex or body weight differences among groups. The implication of these results is that the presence of depressive symptoms may affect cocaine use behavior partly by being associated with an enhanced response to cocaine.

Intravenous cocaine increases plasma epinephrine and norepinephrine in humans.

Cocaine has been shown to activate the sympathoadrenal system in both animal and human studies. Controlled human studies have found inconclusive results regarding whether acute cocaine treatment elevates plasma epinephrine and norepinephrine concentrations. The purpose of this study was to investigate whether commonly abused doses of cocaine increase plasma epinephrine and norepinephrine concentrations in humans, in a double-blind, placebo-controlled study. Five male cocaine users were given an intravenous injection of 0.46 mg/kg dose of cocaine or placebo, on two consecutive days. Plasma epinephrine and norepinephrine concentrations were significantly increased in response to cocaine injection compared to placebo. Peak plasma epinephrine and norepinephrine concentrations were reached 3 and 12 min after cocaine injection, respectively. While changes in epinephrine levels following cocaine were correlated with systolic blood pressure and heart rate changes, changes in plasma norepinephrine were correlated with diastolic blood pressure and heart rate changes following cocaine administration. These results suggest that plasma epinephrine and norepinephrine can be used as a measure for cocaine induced sympathoadrenal system activation.

Characteristics of research volunteers for inpatient cocaine studies: focus on selection bias.

In order to investigate the selection bias of subjects for inpatient human cocaine studies, characteristics of 859 potential subjects were examined. Excluded subjects compared with accepted group were more likely to be single and male, currently use drugs other than cocaine, have a history of intravenous cocaine use, and have medical or mental health problems or physical complaints. Subjects who were accepted but did not participate, compared with participants, were likely to spend more money on cocaine. These results suggest that potential subjects who were accepted to our research studies may not accurately represent all potential subjects for several important subject characteristics.

Carvedilol affects the physiological and behavioral response to smoked cocaine in humans.

The noradrenergic system is implicated in mediating some of the physiological effects of cocaine. The purpose of this study was to investigate whether treatment with an adrenergic blocker, carvedilol, which would be expected to attenuate the physiological effects of cocaine, would also attenuate the subjective and behavioral response to cocaine in humans. Twelve crack cocaine users participated in this double-blind, placebo-controlled outpatient study. Acute treatment with 50 mg of oral carvedilol attenuated the smoked cocaine-induced increases in heart rate, systolic and diastolic blood pressure. The number of cocaine self-administrations was lower under 25 mg carvedilol treatment condition compared with 50 mg carvedilol or placebo treatment conditions. The subjective responses to smoked cocaine deliveries were not affected by carvedilol treatment. These results suggest that acute treatment with carvedilol attenuates the physiological effects of smoked cocaine. The effects of carvedilol on cocaine self-administration need to be studied further.

Effects of labetalol treatment on the physiological and subjective response to smoked cocaine.

Adrenergic receptors mediate some of the physiological and possibly behavioral effects of cocaine. The purpose of this study was to investigate the effect of treatment with a peripherally acting adrenergic blocking drug labetalol on the cardiovascular and subjective response to repeated deliveries of smoked cocaine. In this double-blind, placebo-controlled, crossover study, 12 cocaine users were treated with a single 100 or 200 mg dose of labetalol, or placebo in each of three experimental sessions. Starting 2 h after the medication treatment, subjects received three doses of 0.4 mg/kg smoked cocaine, 30 min apart. Labetalol treatment significantly attenuated the cocaine-induced increases in heart rate and systolic blood pressure. This effect of labetalol on the cardiovascular response did not decrease with repeated cocaine deliveries. The subjective response to smoked cocaine deliveries was not affected by labetalol treatment. These results suggest that labetalol effectively attenuates the systolic blood pressure and heart rate increases induced by repeated doses of smoked cocaine, but does not alter subjective effects.