Marlene Busko

December 12, 2008

December 12, 2008 (Boca Raton, Florida) — In a laboratory study of cocaine users, progesterone reduced craving and the feeling of being stimulated by cocaine, researchers report.

Progesterone also decreased cocaine-induced systolic blood pressure (BP) elevation but did not diminish the feeling of being high, lower cocaine-induced heart rate, or lower the elevation of diastolic BP.

Men had a greater increase in diastolic BP and more heart racing and reported feeling higher and more stimulated than women in response to cocaine, whereas women had more craving.

These results from an off-label study of progesterone in 38 cocaine-dependent subjects were presented here at the American Academy of Addiction Psychiatry 19th Annual Meeting and Symposium by primary investigator Sheila Specker, MD, from the University of Minnesota, in Minneapolis.

"This larger within-subjects design provides additional support for an effect of progesterone on subjective and physiological effects of cocaine," she told conference attendees.

However, she added, there is a need for continued investigation into sex differences and variability in craving and use across the menstrual cycle.

Major Problem

Cocaine abuse remains a major problem in men and women, and medications have had minimal effect.

Previous research identified sex differences in cocaine-use patterns and physiological effects, suggesting that sex hormones play a role in craving and addiction.

Progesterone, which has a gamma-aminobutyric acid (GABA) agonist active metabolite, was proposed as an agent that might decrease cocaine craving by reducing the dopaminergic properties of the drug.

In addition, preclinical research has shown that progesterone decreases self-administration of cocaine in animals, and several clinical studies support these findings. However, these earlier studies did not always separate the effects of estrogen from progesterone, had small sample sizes, or looked at a single sex.

To examine the effect of progesterone on cocaine craving, self-administration, and physiological response, the researchers conducted an in-laboratory trial.

The study included 21 men and 17 women with a mean age of 40 years who had been using cocaine for 15 years. The subjects had used cocaine, alcohol, and cannabis an average of 15.6, 6.5, and 4.3 days of the previous 30 days, respectively.

The subjects participated in 2 in-patient 4-day experimental sessions, 1 month apart.

Participants were randomized to receive 200 or 400 mg of progesterone or placebo on day 1. On day 2, they adapted to this medication. On days 3 and 4, they participated in 3-hour experiments in which every 30 minutes they could choose to receive either $5 or a dose of cocaine.

The subjects returned for a second similar experimental session 1 month later.

The primary outcome variables were Cocaine Effects Questionnaire responses about craving, feeling stimulated, feeling the effect of the last dose, feeling high, or having a racing heart; physiological measures of blood pressure and pulse; and doses of cocaine taken.

Significant, Small Decrease in Craving

Progesterone had no effect on the number of doses taken. It did significantly decrease craving (P < .001), and subjects felt less stimulated (P = .027). It also lowered systolic BP (P < .001) but did not lower diastolic BP or heart rate or diminish the feeling of being high.

"Many factors are likely associated with the decision to use cocaine," said Dr. Specker, noting that although the results were significant, the response was small.

"A laboratory model is a useful method to study and isolate the effects of medications, but the subjects' decisions to self-administer cocaine may be influenced by other factors," she said. Future research should investigate the roles of estrogen, GABA agonists, and opioid blockers and should be larger outpatient studies with more women.

The study was supported by a grant from the National Institute on Drug Abuse. Dr. Specker has disclosed no relevant financial relationships.

American Academy of Addiction Psychiatry 19th Annual Meeting and Symposium: Paper Presentation Session 1. Presented December 7, 2008.

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