Response, Addiction to Cocaine Hinge on Gender

Men tend to obtain higher plasma cocaine levels from a given dose of inhaled substance, and they tend to experience more euphoria. They are more likely to become addicted and have a far more difficult time shaking cocaine addiction. On average, women absorb less cocaine from a given intranasal dose and experience much less euphoria. This is especially true during the luteal phase of the menstrual cycle.

Women who do use cocaine, however, are much more likely than men to experience cardiotoxic effects. At any given inhaled dose, women absorb less, but they have heart rate changes that are nearly identical to those seen in men, said Dr. Lukas, professor of psychiatry and pharmacology at Harvard Medical School, Boston.

Tachycardia, sometimes life threatening, is a very common effect of cocaine use in women. “Emergency room admissions for cocaine-related heart palpitations are on the order of six females for every one male,” he said.

He and other researchers studying gender response to illicit drugs believe that these differences are largely influenced by sex hormones. In 1971, pioneering stress physiologist Hans Selye suggested that hormones regulate resistance to various drugs and toxins. The hormonal effects, however, can cut both ways.

Dr. Lukas explained that the nasal mucosa is under sex hormone control, just as the uterine mucosa is. Estrogen increases nasal mucosal thickness, as well as the viscosity of nasal mucosal secretions. Presumably, this would lower intranasal absorption of cocaine.

A study published in 1999 by other investigators documented gender-based differences in response to 0.9-mg/kg doses of intranasal cocaine. The data showed that men consistently had higher plasma levels and reported more intense subjective experiences of the cocaine high.

At the 0.9-mg/kg dose, men showed plasma levels of 150 ng/mL at 30–40 minutes, while women in the follicular phase had plasma levels of only 70 ng/mL from the same intranasal dose.

Women who were in the luteal phase had even lower plasma concentrations. The men and women had equivalent changes in heart rate.

“Men have a pretty immediate euphoric response to cocaine, and then an hour later they have a marked crash characterized by a lot of dysphoria. Women get a lot less euphoria, especially during the luteal phase,” he said at the meeting cosponsored by the New York Academy of Medicine

Given this differential in dose absorption, it is fairly easy to understand how this translates into cardiac problems for women who use cocaine. Dr. Lukas asked attendees to imagine a young couple out on a date.

“He wants to do some coke, and he's very excited about it. He snorts a line or two and gives the same to his girlfriend. He's immediately revved up, while she's not feeling very much. So he keeps giving her more and more, hoping she'll reach his level of euphoria.” All too often, though, the young woman ends up reaching a frightening level of tachycardia and has to go to the hospital, he said.

Progesterone appears to exacerbate the cardiotoxic effects of cocaine. This has been shown in rodent experiments and in studies of pregnant women using cocaine. Dr. Lukas said the progesterone effect might account in part for the observation that women have heart rate changes similar to those in men despite having lower plasma levels.

Because men are more likely to have immediate euphoric responses to cocaine, they are naturally more inclined to repeat an initial positive experience, leading to an increased risk of addiction.

According to James Anthony, Ph.D., chairman of epidemiology at Michigan State University, East Lansing, national statistics show that men are far more likely to become cocaine dependent, and they are also more likely than women to try crack cocaine.

Dr. Lukas cited a single-photon emission computed tomography study of brain changes in cocaine-dependent men and women. The study showed that men had far more detectable brain damage than the women.

“In effect, the men had lots of ministrokes all over the brain. Women had some, but far [fewer] of them,” Dr. Lukas said.

Men showed more cerebral vasoconstriction, compared with women, and overall, they were more sensitive to the brain-damaging effects of cocaine.

For reasons that are not entirely clear, men using cocaine have much greater difficulty with detoxification, he said, not that detoxification is easy for cocaine-dependent women. In general, however, women become drug free more quickly and have better long-term, drug-free response rates.

Dr. Lukas, who has conducted several studies of drug abuse among women, stressed the importance of doing this kind of research, while also acknowledging the considerable difficulties of doing drug studies in females.

“The female body is so much more complex than the male's. Men are far easier to study. With women, there are more hormonal cycles going on, menstrual cycle phases, and pregnancy, body mass, and dosing issues.

“And there are the issues related to prepubertal vs. childbearing age vs. menopausal stages of life. And of course, you have to take into account use of oral contraceptives or hormone replacement therapy,” he said.

Drug research on women is expensive. He noted that it costs between $1,200 and $1,500 in pretrial blood work just to determine whether a woman can participate in a trial.

And there's the ongoing need for pregnancy testing.

“I can't say enough about this. Testing once at the beginning of a yearlong study is not sufficient. In our lab, we're doing cocaine and alcohol studies. Anytime a woman in one of our studies comes to my lab, she gets a pregnancy test. “In the last decade, I've detected six women who [came] to the lab to take cocaine or alcohol and did not know they were pregnant. Testing adds to the cost of a study, but it is money well spent. You don't want to unwittingly give cocaine to a woman who's pregnant,” Dr. Lukas said.

Men tend to obtain higher plasma cocaine levels from a given dose of inhaled substance, and they tend to experience more euphoria. They are more likely to become addicted and have a far more difficult time shaking cocaine addiction. On average, women absorb less cocaine from a given intranasal dose and experience much less euphoria. This is especially true during the luteal phase of the menstrual cycle.

Women who do use cocaine, however, are much more likely than men to experience cardiotoxic effects. At any given inhaled dose, women absorb less, but they have heart rate changes that are nearly identical to those seen in men, said Dr. Lukas, professor of psychiatry and pharmacology at Harvard Medical School, Boston.

Tachycardia, sometimes life threatening, is a very common effect of cocaine use in women. “Emergency room admissions for cocaine-related heart palpitations are on the order of six females for every one male,” he said.

He and other researchers studying gender response to illicit drugs believe that these differences are largely influenced by sex hormones. In 1971, pioneering stress physiologist Hans Selye suggested that hormones regulate resistance to various drugs and toxins. The hormonal effects, however, can cut both ways.

Dr. Lukas explained that the nasal mucosa is under sex hormone control, just as the uterine mucosa is. Estrogen increases nasal mucosal thickness, as well as the viscosity of nasal mucosal secretions. Presumably, this would lower intranasal absorption of cocaine.

A study published in 1999 by other investigators documented gender-based differences in response to 0.9-mg/kg doses of intranasal cocaine. The data showed that men consistently had higher plasma levels and reported more intense subjective experiences of the cocaine high.

At the 0.9-mg/kg dose, men showed plasma levels of 150 ng/mL at 30–40 minutes, while women in the follicular phase had plasma levels of only 70 ng/mL from the same intranasal dose.

Women who were in the luteal phase had even lower plasma concentrations. The men and women had equivalent changes in heart rate.

“Men have a pretty immediate euphoric response to cocaine, and then an hour later they have a marked crash characterized by a lot of dysphoria. Women get a lot less euphoria, especially during the luteal phase,” he said at the meeting cosponsored by the New York Academy of Medicine

Given this differential in dose absorption, it is fairly easy to understand how this translates into cardiac problems for women who use cocaine. Dr. Lukas asked attendees to imagine a young couple out on a date.

“He wants to do some coke, and he's very excited about it. He snorts a line or two and gives the same to his girlfriend. He's immediately revved up, while she's not feeling very much. So he keeps giving her more and more, hoping she'll reach his level of euphoria.” All too often, though, the young woman ends up reaching a frightening level of tachycardia and has to go to the hospital, he said.

Progesterone appears to exacerbate the cardiotoxic effects of cocaine. This has been shown in rodent experiments and in studies of pregnant women using cocaine. Dr. Lukas said the progesterone effect might account in part for the observation that women have heart rate changes similar to those in men despite having lower plasma levels.

Because men are more likely to have immediate euphoric responses to cocaine, they are naturally more inclined to repeat an initial positive experience, leading to an increased risk of addiction.

According to James Anthony, Ph.D., chairman of epidemiology at Michigan State University, East Lansing, national statistics show that men are far more likely to become cocaine dependent, and they are also more likely than women to try crack cocaine.

Dr. Lukas cited a single-photon emission computed tomography study of brain changes in cocaine-dependent men and women. The study showed that men had far more detectable brain damage than the women.

“In effect, the men had lots of ministrokes all over the brain. Women had some, but far [fewer] of them,” Dr. Lukas said.

Men showed more cerebral vasoconstriction, compared with women, and overall, they were more sensitive to the brain-damaging effects of cocaine.

For reasons that are not entirely clear, men using cocaine have much greater difficulty with detoxification, he said, not that detoxification is easy for cocaine-dependent women. In general, however, women become drug free more quickly and have better long-term, drug-free response rates.

Dr. Lukas, who has conducted several studies of drug abuse among women, stressed the importance of doing this kind of research, while also acknowledging the considerable difficulties of doing drug studies in females.

“The female body is so much more complex than the male's. Men are far easier to study. With women, there are more hormonal cycles going on, menstrual cycle phases, and pregnancy, body mass, and dosing issues.

“And there are the issues related to prepubertal vs. childbearing age vs. menopausal stages of life. And of course, you have to take into account use of oral contraceptives or hormone replacement therapy,” he said.

Drug research on women is expensive. He noted that it costs between $1,200 and $1,500 in pretrial blood work just to determine whether a woman can participate in a trial.

And there's the ongoing need for pregnancy testing.

“I can't say enough about this. Testing once at the beginning of a yearlong study is not sufficient. In our lab, we're doing cocaine and alcohol studies. Anytime a woman in one of our studies comes to my lab, she gets a pregnancy test. “In the last decade, I've detected six women who [came] to the lab to take cocaine or alcohol and did not know they were pregnant. Testing adds to the cost of a study, but it is money well spent. You don't want to unwittingly give cocaine to a woman who's pregnant,” Dr. Lukas said.

Men tend to obtain higher plasma cocaine levels from a given dose of inhaled substance, and they tend to experience more euphoria. They are more likely to become addicted and have a far more difficult time shaking cocaine addiction. On average, women absorb less cocaine from a given intranasal dose and experience much less euphoria. This is especially true during the luteal phase of the menstrual cycle.

Women who do use cocaine, however, are much more likely than men to experience cardiotoxic effects. At any given inhaled dose, women absorb less, but they have heart rate changes that are nearly identical to those seen in men, said Dr. Lukas, professor of psychiatry and pharmacology at Harvard Medical School, Boston.

Tachycardia, sometimes life threatening, is a very common effect of cocaine use in women. “Emergency room admissions for cocaine-related heart palpitations are on the order of six females for every one male,” he said.

He and other researchers studying gender response to illicit drugs believe that these differences are largely influenced by sex hormones. In 1971, pioneering stress physiologist Hans Selye suggested that hormones regulate resistance to various drugs and toxins. The hormonal effects, however, can cut both ways.

Dr. Lukas explained that the nasal mucosa is under sex hormone control, just as the uterine mucosa is. Estrogen increases nasal mucosal thickness, as well as the viscosity of nasal mucosal secretions. Presumably, this would lower intranasal absorption of cocaine.

A study published in 1999 by other investigators documented gender-based differences in response to 0.9-mg/kg doses of intranasal cocaine. The data showed that men consistently had higher plasma levels and reported more intense subjective experiences of the cocaine high.

At the 0.9-mg/kg dose, men showed plasma levels of 150 ng/mL at 30–40 minutes, while women in the follicular phase had plasma levels of only 70 ng/mL from the same intranasal dose.

Women who were in the luteal phase had even lower plasma concentrations. The men and women had equivalent changes in heart rate.

“Men have a pretty immediate euphoric response to cocaine, and then an hour later they have a marked crash characterized by a lot of dysphoria. Women get a lot less euphoria, especially during the luteal phase,” he said at the meeting cosponsored by the New York Academy of Medicine

Given this differential in dose absorption, it is fairly easy to understand how this translates into cardiac problems for women who use cocaine. Dr. Lukas asked attendees to imagine a young couple out on a date.

“He wants to do some coke, and he's very excited about it. He snorts a line or two and gives the same to his girlfriend. He's immediately revved up, while she's not feeling very much. So he keeps giving her more and more, hoping she'll reach his level of euphoria.” All too often, though, the young woman ends up reaching a frightening level of tachycardia and has to go to the hospital, he said.

Progesterone appears to exacerbate the cardiotoxic effects of cocaine. This has been shown in rodent experiments and in studies of pregnant women using cocaine. Dr. Lukas said the progesterone effect might account in part for the observation that women have heart rate changes similar to those in men despite having lower plasma levels.

Because men are more likely to have immediate euphoric responses to cocaine, they are naturally more inclined to repeat an initial positive experience, leading to an increased risk of addiction.

According to James Anthony, Ph.D., chairman of epidemiology at Michigan State University, East Lansing, national statistics show that men are far more likely to become cocaine dependent, and they are also more likely than women to try crack cocaine.

Dr. Lukas cited a single-photon emission computed tomography study of brain changes in cocaine-dependent men and women. The study showed that men had far more detectable brain damage than the women.

“In effect, the men had lots of ministrokes all over the brain. Women had some, but far [fewer] of them,” Dr. Lukas said.

Men showed more cerebral vasoconstriction, compared with women, and overall, they were more sensitive to the brain-damaging effects of cocaine.

For reasons that are not entirely clear, men using cocaine have much greater difficulty with detoxification, he said, not that detoxification is easy for cocaine-dependent women. In general, however, women become drug free more quickly and have better long-term, drug-free response rates.

Dr. Lukas, who has conducted several studies of drug abuse among women, stressed the importance of doing this kind of research, while also acknowledging the considerable difficulties of doing drug studies in females.

“The female body is so much more complex than the male's. Men are far easier to study. With women, there are more hormonal cycles going on, menstrual cycle phases, and pregnancy, body mass, and dosing issues.

“And there are the issues related to prepubertal vs. childbearing age vs. menopausal stages of life. And of course, you have to take into account use of oral contraceptives or hormone replacement therapy,” he said.

Drug research on women is expensive. He noted that it costs between $1,200 and $1,500 in pretrial blood work just to determine whether a woman can participate in a trial.

And there's the ongoing need for pregnancy testing.

“I can't say enough about this. Testing once at the beginning of a yearlong study is not sufficient. In our lab, we're doing cocaine and alcohol studies. Anytime a woman in one of our studies comes to my lab, she gets a pregnancy test. “In the last decade, I've detected six women who [came] to the lab to take cocaine or alcohol and did not know they were pregnant. Testing adds to the cost of a study, but it is money well spent. You don't want to unwittingly give cocaine to a woman who's pregnant,” Dr. Lukas said.