Volume 11, Number 1
Cocaine Affects Men and Women Differently, NIDA Study Shows
By John A. Bowersox, NIDA NOTES Contributing Writer
A recent NIDA-funded study suggests that gender differences will become an increasingly important consideration in drug abuse treatment strategies. The study by researchers affiliated with Harvard Medical School found that cocaine affects men and women differently and that hormonal fluctuations play an important role in women's responses to the drug.
In the study, Dr. Scott E. Lukas and his colleagues at the Alcohol and Drug Abuse Research Center in Belmont, Massachusetts, measured a variety of responses to cocaine in six male and six female volunteers. On separate days, the volunteers snorted single doses of cocaine and placebo powder in equal amounts relative to their body weights. The men were tested once, but the women were tested at two different times during their menstrual cycle: once during their follicular phase and again during their luteal phase. The follicular and luteal phases, respectively, correspond to the times before and after ovulation. The researchers calculated the phases of each woman's cycle from the onset of menstruation:
- Dose 1 (midfollicular phase) was given 5 to 9 days after the onset of menstruation;
- Dose 2 (midluteal phase) was given 18 to 22 days after onset of menstruation.
The researchers found that at both points in the menstrual cycle the women were much less sensitive to the drug than the men were. The men in the study had significantly more episodes of euphoria, or good feelings, and dysphoria, or bad feelings. When asked to rate the severity of their dysphoria, the men judged the bad feelings to be more unpleasant than the women did. The men also experienced greater heart rate and blood pressure increases and detected cocaine's effects sooner than the women did. Although the men and women received equivalent doses of cocaine, women had lower levels of the drug in their blood than the men; their cocaine blood levels were even lower when they took the drug during the luteal phase of their menstrual cycle.
Dr. Lukas says that differences in the speed with which cocaine is metabolized may account for the drug's different effects in men and women. In the body, cocaine is broken down into inactive metabolites by enzymes known as cholinesterases. Although men have higher levels of these enzymes in their blood plasma, women have higher levels of a type of cholines-terase enzyme found in red blood cells, Dr. Lukas explains. The red blood cell enzyme metabolizes cocaine much more actively than the plasma enzyme does.
Physical changes that occur during the menstrual cycle also may contribute to women's decreased sensitivity to intranasal cocaine, says Dr. Lukas. The increase in certain hormone levels during the luteal phase causes women's mucous membranes, including those that line the nasal passages, to secrete more mucus. Dr. Lukas says that the increased mucus may act as a barrier to the absorption of cocaine when women snort the drug during the luteal phase of their menstrual cycle.
"We believe that the gender differences in cocaine's effects that we observed are due to a combination of metabolic differences and the greater physical barrier to cocaine absorption created by the increase in mucosity," says Dr. Lukas. He adds that other as yet unknown factors could also help produce cocaine's differing effects.
Dr. Lukas says the findings, which he presented at the 1994 meeting of the College on Problems of Drug Dependence, might help explain, at least from a physiological perspective, why the prevalence of cocaine use among women has traditionally been much lower than it has been among men. According to the National Household Survey on Drug Abuse, approximately 3.1 million men and 1.4 million women used cocaine at least once during 1993. Women also appear to take cocaine less frequently than men do. The 1993 survey, which was conducted by the Substance Abuse and Mental Health Services Administration, estimates that about 365,000 men compared with 111,000 women used cocaine at least once a week.
Many women have reported that they did not get high when they first tried cocaine, says Dr. Lukas, adding that women's low sensitivity to the drug combined with its high price create a strong disincentive to its continued use. On the other hand, he says, some women may become heavy users because they need to take more cocaine to get the same effect as men.
If further studies substantiate Dr. Lukas' findings, they could have important implications for the treatment of cocaine abusers, says Dr. Elizabeth Rahdert, a research psychologist in NIDA's Division of Clinical and Services Research.
"Therapists would have to realize that for women, the response to cocaine will be different at different times of the month and not a steady state as it is for men," she says.
Presumably, she adds, patterns of craving and response to withdrawal could also fluctuate with a woman's menstrual cycle, and treatment professionals would have to recognize that women could be more vulnerable to relapse at different points in their cycle. Furthermore, treatment strategies designed to address male usage patterns would have to be modified in accordance with women's usage patterns.
Dr. Lukas' work reflects NIDA's increased interest in examining the gender-specific effects of drug abuse. Basic research findings such as the discovery that sex hormones can interact with neurotransmitters during normal brain functioning have fueled this interest.
"Previously, drug abuse research on women focused mainly on issues related to pregnancy and the effects of drug abuse on the developing fetus," says Dr. Cora Lee Wetherington, a psychologist in NIDA's Division of Basic Research.
"More recently, we've seen a shift with the realization that the treatment needs of women may be different from those of men. Although issues related to childbearing and child-rearing are still important areas of drug abuse research, researchers are questioning whether treatment strategies that were developed through research conducted largely on male subjects are appropriate for women," says Dr. Wetherington.
Lukas, S.E.; Sholar, M.B.; Fortin, M.; Wines, J., Jr.; and Mendelson, J.H. Sex differences in plasma cocaine levels and subjective effects after acute cocaine administration in human volunteers. Psychopharmacology, in press.
From NIDA NOTES, January/February, 1996
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