By Jill S. Williams, NIDA NOTES Contributing Writer
Researchers studying the effects of cocaine on the brain have
found that men and women with comparable drug use histories do
not exhibit comparable damage. One study showed that women suffered
less neuronal injury than men; another, that cocaine-dependent
women have fewer abnormalities in blood flow to the brain than
do cocaine-dependent men. Now, a recent NIDA-funded study has
taken an important step toward explaining these differences between
Magnetic resonance (MR) image intensity
was measured to compare the hemodynamic effects of cocaine
during two phases of a woman's menstrual cycle. Following
cocaine administration during the follicular phase,
image intensity was relatively high, reflecting cerebral
blood flow at 97 percent of its pre-cocaine baseline.
When the drug was given during the luteal phase, lower
image intensity reflected a fall in blood flow to 82
percent of baseline. The MR technique is illustrated
on page 6.
Cocaine constricts blood vessels, temporarily narrowing arteries
and reducing blood flow to the brain, heart, and other areas of
the body. Repeated exposure to cocaine can lead to blood-flow
deficits in the brain that persist long after cocaine use has
ended, causing permanent damage.
Dr. Marc J. Kaufman and colleagues at McLean Hospital, Harvard
Medical School, in Belmont, Massachusetts, found that cerebral
blood flow during the follicular phase of women's menstrual cycles
(days 1 through 14, prior to ovulation) is not affected by exposure
to cocaine. In women during their luteal phase (after ovulation,
typically days 15 through 28) and in men, cocaine restricts cerebral
"We hypothesized that the differences in blood flow might
be caused by sex hormones," says Dr. Kaufman. "We decided
to investigate whether women with high levels of estrogen, which
improves blood-vessel elasticity, are more resistant to the vasoconstrictive
effects of cocaine."
Dr. Kaufman and his colleagues used dynamic susceptibility contrast
magnetic resonance imaging (DSC MRI) to study cocaine-induced
changes in cerebral blood volume in 13 healthy young women (average
age 28) with histories of occasional cocaine use. The women's
self-reported lifetime cocaine use averaged 13 exposures (ranging
from 1 to 40).
Each woman was given a dose of cocaine and underwent a DSC MRI
scan of cerebral blood volume during both phases of her menstrual
cycle. During the first part of the menstrual cycle, estrogen
levels are high and progesterone levels are low; during the second
part, progesterone levels rise. In each imaging session, two brain
images were collected: one as a baseline measure of cerebral blood
volume and the second 10 minutes after cocaine administration.
The study found no significant changes in cerebral blood volume
after cocaine administration during the women's follicular phase.
During the luteal phase, when progesterone levels are highest,
the women's cerebral blood flow fell approximately 10 percent
after cocaine administration. These data compare to Dr. Kaufman's
findings in a similar 1998 study, that men experience, on average,
a 20-percent reduction in cerebral blood volume after cocaine
A sequence of magnetic resonance images
taken at 1-second intervals after a woman received an intravenous
blood marker progresses from light to dark to light as her
cerebral blood flow carries the marker into her brain and
washes it back out again. The total marker present in all
the images, measured as their intensity (darkness), reflects
total cerebral blood volume. To study the hemodynamic effects
of cocaine, investigators compared two such sequences, obtained
before and after administration of the drug, during each menstrual
"We found what we were expecting," says Dr. Kaufman.
"There was a minimal change in follicular cerebral blood
volume, attributable, we believe, to the protective effects of
estrogen. The greater vasoconstrictive effect of cocaine in luteal-phase
women may be attributable to the progesterone, which has been
shown to increase cocaine's vascular toxicity."
Dr. Kaufman's next step will be to administer estrogen or progesterone
to men and luteal-phase women and measure the effects on cerebral
blood volume after cocaine administration. The ultimate goal will
be to develop a hormonelike medication to counteract the vascular
effects of cocaine.
"Beyond confirming that cocaine does have a damaging effect
on the brain and is not safe to use, this research contributes
to our understanding of the drug's deleterious effects,"
says Dr. Steven Grant, of NIDA's Division of Treatment Research
and Development. "Additionally, the research points out that
we've got to stop thinking of both sexes as the same when it comes
to the effects of drugs. Dr. Kaufman has shown that cocaine affects
men and women differently."
- Kaufman, M., et al. Cocaine-induced cerebral vasoconstriction
differs as a function of sex and menstrual cycle phase. Biological
Psychiatry 49(9):774-781, 2001. [Abstract]
- Kaufman, M., et al. Cocaine decreases relative cerebral blood
volume in humans: A dynamic susceptibility contrast magnetic
resonance imaging study. Psychopharmacology 138:76-81,
Volume 17, Number 2 (May 2002)