Category: Illegal Drugs

Steroid Use Causes Long-term Agression, Northeastern University Report Indicates

 BOSTON, Mass. (11-20-03) -– With the recent revelations about steroid use in Major League Baseball and the bust last week of several Oakland Raiders players for drug abuse, Northeastern University psychology professor Richard Melloni, who studies the link between steroid use and aggression, has recently found evidence that use of anabolic steroids may have long-term effects on behavior and aggression levels well after they stop abusing these performance enhancing drugs.

With funding from the NIH (recently extended through 2008), Melloni and doctoral student Jill Grimes have been studying how steroids used during adolescence may permanently alter the brain's ability to produce serotonin. In their experiments, adolescent Syrian hamsters – given their similar brain circuitry to human adolescents – were administered doses of anabolic steroids and then measured for aggressiveness over certain periods of time.

The researchers initially hypothesized that steroid use during adolescence might permanently alter the brain's chemistry and a person's tendency toward aggression long after use has stopped. Their most recent findings, published this week in Hormones and Behavior, enabled them to confirm this hypothesis and conclude that there is indeed a lengthy price – namely long-term aggression – to pay for drug abuse even after the ingestion of steroids ceases.

"We know testosterone or steroids affect the development of serotonin nerve cells, which, in turn, decreases serotonin availability in the brain," Melloni says. "The serotonin neural system is still developing during adolescence and the use of anabolic steroids during this critical period appears to have immediate and longer-term neural and behavioral consequences. What we know at this point is that aggressiveness doesn't simply cease after the ingestion of steroids does."

Based on this research, Melloni also believes that athletes who abuse steroids may also be inclined toward aggressive behavior long after their drug abuse – and musculature – have waned.

Promising Drug Proves Ineffective As Treatment For Hearing Loss

NewsPsychology (Oct. 8, 2003) — Researchers have demonstrated that Methotrexate, a promising drug to treat hearing loss in patients with autoimmune inner ear disease (AIED), proved no more effective than placebo in a recently concluded four-year study.

In findings published in the October 8, 2003 issue of the Journal of the American Medical Association (JAMA), a team headed by University of California, San Diego (UCSD) Professor and Chief of Otolaryngology Head and Neck Surgery, Jeffrey Harris, M.D., also noted that the steroid Prednisione proved very effective in both stabilizing and helping over 57% of the AIED patients regain hearing.

“AIED is a rapidly progressive form of sensorineural hearing loss. If left untreated or treated inadequately, AIED can result in profound deafness,” says Harris. “We’ve known for some time that steroids are effective in improving hearing loss in AIED.”

However, he noted, the many side effects associated with maintaining prolonged steroid therapy has led to the search for more effective drugs to treat this condition over the long term. And, once the steroids are withdrawn, the hearing loss may reoccur. Methotrexate has been considered a promising drug to treat AIED, due to its long track record as an effective anti-inflammatory, says Harris, improving patients with rheumatoid arthritis, an autoimmune disease that affects the body’s joints. Since AIED is also an autoimmune condition, Harris says researchers hoped the drug would have the same therapeutic effect.

AIED starts with the rapid appearance of bilateral, fluctuating and progressive, asymmetrical sensorineural hearing loss. Patients show hearing loss and usually tinnitus. Several blood tests are now being tested to identify patients with AIED. Approximately two-thirds of patients exhibit this autoimmune disease in their ears. In the other third, patients may have some of the well-known rheumatic diseases occurring concurrently with the hearing loss.

“In earlier studies where Methotrexate was used to treat AIED, the initial results appeared positive. The current study was designed to determine in a controlled, double-blind fashion if Methotrexate could maintain the hearing improvement achieved initially with Prednisone,” Harris says.

The study enrolled 116 patients with AIED, treating each of them with one month of high dose Prednisone. At the end of the first phase, 67 who showed significant hearing improvement were randomized to receive either Methotrexate or placebo. Prednisone was slowly tapered in both groups over a 3-month period while the Methotrexate and placebo doses were increased.

The results showed that Methotrexate was no more effective than the placebo in maintaining the hearing gain achieved with Prednisone. Of the 67 patients who went on to receive Methotrexate or placebo, 61 were disqualified from continuing the study due to further hearing losses.

Of the 116 patients who received the initial high dose steroids, 63% responded to Prednisone in one ear while 37% responded in both ears, and the researchers observed that long-term Prednisone was well tolerated under the close management of the treating physicians involved in this study.

Harris says the results underscore the importance of well-controlled studies to test the efficacy of drugs in the treatment of AIED, adding it also demonstrates the urgent need to discover more effective and lasting treatments for this condition that usually leads to acute deafness.

###

The study published in JAMA was sponsored by the National Institute on Deafness and Communication Disorders. Co-authors were Michael H. Weisman, M.D., Cedars-Sinai Medical Center, Los Angeles; Jennifer M. Derebery, M.D., and Ralph A. Nelson, M.D., House Ear Institute, Los Angeles; Mark A. Espeland, PhD, Wake Forest University, Winston-Salem, NC; Bruce J. Gantz, M.D., University of Iowa, Iowa City; A. Julianna Gulya, M.D., National Institute on Deafness and Other Communication Disorders, Bethesda, MD; Paul E. Hammerschlag, M.D., New York University, NYC; Maureen Hannley, PhD, American Academy of Ototlaryngology-Head & Neck Surgery, Alexandria, VA; Gordon B. Hughes, M.D., The Cleveland Clinic, Cleveland, OH, Richard Moscicki, M.D., Massachusetts General Hospital, Boston, MA; John K. Niparko, M.D., Johns Hopkins University, Baltimore, MD; Steven D. Rauch, M.D., Massachusetts Eye and Ear Infirmary, Boston, MA; Steven A. Telian, M.D., University of Michigan, Ann Arbor, MI; and Patrick E. Brookhouser, M.D., Boystown National Research Hospital, Omaha, NE.

Email or share this story:

Story Source:

The above story is reprinted (with editorial adaptations by newsPsychology staff) from materials provided by University Of California – San Diego.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of NewsPsychology or its staff.

Taking Ecstasy During Pregnancy May Cause Brain Damage, Behavior Problems In Babies

Women who take the drug Ecstasy in their first trimester of pregnancy may be putting their unborn child at risk for brain damage, according to a study published in the September issue of the journal Neurotoxicity and Teratology.

Jack W. Lipton, PhD, a neuroscientist at Rush-Presbyterian-St. Luke's Medical Center in Chicago, demonstrated that fetal exposure in rats to the drug Ecstasy during a period analogous to the first trimester in humans causes changes in the young rat's brain chemistry and behavior. The study was funded in part by the National Institute on Drug Abuse (NIDA). Ecstasy also is known as MDMA or 3,4-methylenedioxymethamphetamine.

"The limited data that exist suggest that women who use Ecstasy stop taking it when they learn they are pregnant," says Dr. Nora D. Volkow, director of the NIDA. "But many of the animal studies that linked this drug to neurological changes and learning impairments were conducted in situations analogous to the third trimester in humans. Thus, this study sought to investigate a more true-to-life situation by looking at neurobiological changes caused by Ecstasy early in pregnancy."

The researchers injected the drug twice daily from day 14 through day 20 of pregnancy. An equal number of pregnant rats were given sham injections of saline twice daily during the same period as a placebo. The most striking finding was that 21-day-old Ecstasy exposed rats had a 502% increase in the number of dopamine neuron fibers in the frontal cortex as compared to controls. The frontal cortex is important in planning, impulse control and attention.

Similar but smaller increases in dopaminergic fiber density were also evident in the striatum — an area involved in movement and reward and the nucleus accumbens — the primary site of action of rewarding stimuli. The investigators believe that this hyperinnervation is either due to MDMA-induced reductions in the normal cell loss that occurs during fetal development, or MDMA-induced increases in chemicals known as trophic factors which can mediate growth and survival of brain cells.

Lipton and his colleagues also found that behavioral changes were evident as well. When 21-day-old rats exposed to Ecstasy in the womb were placed in a new environment away from their littermates, they spent significantly more time exploring and did not habituate as easily to the new environment. Such findings suggest that the Ecstasy exposed rats may have learning or attention deficits or alterations in their anxiety levels. Another possibility is that they are simply hyperactive as a result of their in utero exposure.

"Our findings show that exposing rats to Ecstasy at a time of prenatal development that correlates with the first trimester in humans results in lasting changes in brain chemistry and behavior," notes Lipton. "This research warrants the continued monitoring of children exposed to this drug."

Rush-Presbyterian-St. Luke's Medical Center is an academic medical center that encompasses the 824-bed Presbyterian-St. Luke's Hospital (including Rush Children's Hospital), the 110-bed Johnston R. Bowman Health Center and Rush University. Rush University, with more than 1,270 students, is home to one of the first medical schools in the Midwest, one of the nation's top-ranked nursing colleges, as well as graduate programs in allied health and the basic sciences. Rush is noted for bringing together clinical care and research to address major health problems, including arthritis and orthopedic disorders, cancer, heart disease, mental illness neurological disorders and diseases associated with aging.

Rat Study Shows Exposure To Ecstasy Early In Pregnancy Induces Brain, Behavior Changes

Researchers at Rush Presbyterian-St. Luke's Medical Center in Chicago have shown that 21-day-old rat pups exposed in the womb to the drug MDMA (3,4-methylenedioxymethamphetamine, often called Ecstasy) during a period corresponding to the first trimester in human pregnancy exhibit changes in brain chemistry and behavior.

"Existing data suggest that most women who use MDMA stop taking it when they learn they are pregnant," says NIDA Director Dr. Nora D. Volkow. "But the animal studies that linked this drug to neurobiological changes and learning impairments were conducted in situations analogous to the third trimester in humans. This study sought to investigate a more true-to-life situation by looking at the consequences of Ecstasy exposure early in pregnancy."

The study, funded in part by NIDA, was published August 29 on the journal of Neurotoxicology and Teratology Web site.

Dr. Jack W. Lipton, doctoral student James Koprich, and their colleagues injected 8 pregnant rats twice daily with MDMA from day 14 through day 20 of pregnancy, a period corresponding to the first 3 months of human fetal development. The scientists injected saline twice daily during the same period to another 8 pregnant rats. The researchers examined brain tissue of the rat pups when they were 21 days old. A 21-day-old rat pup is roughly equivalent to a 2- to 6-year-old child.

"Our most striking finding was that 21-day-old MDMA-exposed pups had a 502-percent increase in the number of dopamine neuron fibers in the frontal cortex compared with control animals," notes Dr. Lipton. Abnormal or overly numerous connections in the frontal cortex may result in aberrant signaling there, possibly resulting in abnormal behavior.

Dopamine is a brain chemical that carries or transmits messages between nerve cells. It is involved in a variety of motivated behaviors, such as eating, sex, and drug-taking. The frontal cortex is important in planning, impulse control, and attention.

The scientists also saw similar but smaller increases in dopamine fibers in the striatum (a brain area involved in locomotion and reward) and the nucleus accumbens (the primary site of action of rewarding stimuli).

MDMA-exposed pups also showed modest decreases in dopamine metabolism in brain structures that play key roles in reward, addiction, learning, and movement. There also was a reduction in serotonin metabolism. Serotonin also is a brain chemical that helps to regulate mood, sleep, and appetite. Interestingly, the reductions in dopamine and serotonin metabolism that were observed in the nucleus accumbens were evident in male, but not female, pups suggesting sex differences in vulnerability to some of MDMA's prenatal effects.

The rat pups also exhibited behavioral changes. When the Ecstasy-exposed pups were placed in a new environment away from their littermates, they spent significantly more time exploring, signifying they did not adjust as easily to the new environment as the control animals.

"Our findings show that exposing rats to Ecstasy at a time of prenatal development that correlates with the first trimester in humans may result in lasting changes in brain chemistry and behavior," notes Dr. Lipton. "Our findings also suggest that MDMA exposure may result in hyperactivity or deficits in attention or learning. Further research is needed to learn more about the effects of prenatal exposure to this drug."

The National Institute on Drug Abuse is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports more than 85 percent of the world's research on the health aspects of drug abuse and addiction. The Institute carries out a large variety of programs to ensure the rapid dissemination of research information and its implementation in policy and practice. Fact sheets on the health effects of drugs of abuse and information on NIDA research and other activities can be found on the NIDA home page at http://www.drugabuse.gov

Research Links Adolescent Steroid Use To Reduction In Serotonin, Altered Signaling

BOSTON, Mass. — With more than one in ten boys admitting to using steroids, muscle- and strength-enhancing drug use among teenagers has caused considerable concern among parents and researchers over the past decade, but until now, the longer-term physiological and neurological effects of its use on the developing brain have not been fully examined. Now, new research from Northeastern University, published in the latest issue of the journal Pharmacology, Biochemistry and Behavior, documents the link between adolescent anabolic steroid use and aggression and partly associates the increases in aggression with deficits in the brain"s serotonin system. The study will examine longer-term deficiencies of serotonin levels in the brain as a result of damage from steroid use, suggesting that a tendency toward aggression and impulsiveness may actually linger long after both the steroid use and the muscles and strength developed have waned.

With funding from the National Institute of Health, Northeastern University psychology professor Richard Melloni and graduate student Jill Grimes examined the phenomenon of long-term steroid use through a series of experiments on groups of adolescent male Syrian hamsters. During adolescence, this particular breed of hamster displays a natural form of territorial aggression, has similar neurological circuitry to human beings and similar aggression and dominance patterns during its adolescent years, making it a natural model for neurological and behavioral experiments.

During the first experiment, the researchers administered a "high dose" of anabolic steroids to adolescent hamsters over the course of a month, a period corresponding to five years repeated dosage in human adolescents. Those hamsters given steroids were, as other studies have shown, more aggressive than those not treated with steroids.

In the second stage of the experiment, the researchers administered fluoxtine (Prozac), commonly used in treating depression in humans by encouraging the presence of serotonin (the "feel good" receptor), to the hamsters treated with chronic levels of steroids, and found that the previously aggressive tendencies were notably decreased. As in humans, aggressions were mellowed in the presence of Prozac, or serotonin.

Finally, the brains of the anabolic steroid-treated hamsters were examined under a microscope to determine the effect the drugs have on the developing nervous system. In those animals exposed to steroids, significantly lower levels of serotonin were present in the neural connections in their brains, particularly in areas related to aggression and violence.

Melloni and his students plan to conduct a series of follow-up experiments to examine whether the observed serotonin deficits in light of steroid use cause permanent and irreversible damage to the brain and how the neural abnormalities of adolescent anabolic steroid use may affect humans into adulthood. The researchers hypothesize that steroid exposure during adolescence decreases naturally occurring levels of the feel good receptor serotonin particularly in the hypothalamus, the area of the brain pinpointed for aggression and violence, and they plan to conduct a series of follow-up experiments to examine whether the serotonin deficiencies linger and what the longer-term abnormalities of adolescent steroid use actually are into adulthood.

"We know testosterone or steroids affect the development of serotonin nerve cells, which, in turn, decreases serotonin availability in the brain," Melloni said. "The serotonin neural system is still developing during adolescence and the use of anabolic steroids during this critical period appears to have immediate neural and behavioral consequences. Further research will allow us to determine whether or not these deficits are present into adulthood."

Continued steroid use during adolescence is linked not only to aggression and violence, but to a host of physiological problems, including liver diseases, problems with physical growth and development, and sexual dysfunction. Melloni notes that there is currently no long-term understanding of the effects of certain drug use on young people, and that drugs like Ritalin, among others, have no research indicating what aftereffects remain well into adulthood.

Steroid use, he says, is considerably on the rise, with more than ten percent of boys and three percent of girls admitting to regular use.

"Given the fact that we know so little about steroid"s long-term effects, the prospect of results from our research will be doubtlessly interesting and perhaps even frightening," Melloni said. "Perhaps through this sort of research we"ll be able to decrease the popularity of steroid use among teenagers."

Northeastern University, a private research institution located in Boston, Massachusetts, is a world leader in practice-oriented education. Building on its flagship cooperative education program, Northeastern links classroom learning with workplace experience and integrates professional preparation with study in the liberal arts and sciences. For more information, please visit http://www.northeastern.edu

Methamphetamine Drastically Increases Virus Ability To Replicate In Brain Tissue

COLUMBUS, Ohio – A controversial research study here has found that exposing cells infected with feline immunodeficiency virus – a surrogate for HIV – to methamphetamine increases those cells' ability to replicate the deadly virus as much as 15-fold.

The finding, if confirmed by ongoing animal studies, could answer important questions about how lentiviruses such as FIV and HIV can gain a foothold in the brain. That knowledge is vital in slowing or lessening the dementia that often accompanies AIDS and similar diseases.

Ohio State University researchers reported this finding in a paper to be published in the next issue of the Journal of NeuroVirology.

The paper also reports that before a nerve cell can become infected with the virus, it must be associated with a specific type of lymphocyte, or immune cell. Lastly, the researchers discovered that once the virus infects the cells, it mutates into a form that no longer needs this immune-cell association to reproduce.

"We found that after about two weeks of chronic methamphetamine exposure, the ability of these infected cell lines to mass-produce virus increases dramatically," explained Michael Podell, a professor of veterinary clinical sciences and neurosciences.

The concentration of the drug the cells were exposed to was equal to an average level of methamphetamine in an adult abuser's bloodstream, Podell said.

Like HIV, or human immunodeficiency virus, FIV belongs to a family of pathogens called lentiviruses. Lentivirus infections are particularly problematic since these viruses can escape detection by a healthy immune system, mutate quickly and lead to life-long infections in the host, Podell said.

FIV is one of the principal stand-ins for studies of HIV since the viruses are closely related. Studies of this kind using HIV cannot be done safely or ethically in humans.

Viruses spread within the body by first breaching the cell wall and taking up residence within the cellular environment. Once there, the virus begins replicating, or reproducing, until its numbers are so great the cell literally bursts, spreading the virus to nearby cells and throughout the bloodstream.

The Ohio State researchers focused on astrocytes, nerve cells that may make up as much as half of the brain but which for a long time were thought to play a minimal role. Recent research has shown that astrocytes are among the most important cells in the brain and may play a key role in immunity. While scientists had known that FIV and HIV could infect astrocytes, they believed the infection was merely a latent one with the virus remaining almost in dormancy.

Podell, along with colleagues Lawrence Mathes, professor of veterinary biosciences and director of OSU's Center for Retroviral Research, and Mikhail A. Gavrilin, a research scientist in the Department of Veterinary Clinical Sciences, found that FIV is only able to infect astrocytes when they are associated with a peripheral blood mononuclear cell, or PBMC.

A receptor molecule on the astrocyte's cell membrane allows the virus to enter the astrocyte, the researchers found. Both FIV and HIV are able to use the same receptor – CXCR4 – on astrocytes and on immune system cells. They believe CXCR4 may be the principal receptor for all lentiviruses on astrocytes.

The researchers noticed that once it had infected the astrocytes, the virus began to rapidly reproduce – an observation that was contrary to scientists' belief that FIV resulted only in a latent infection. "We found that the reason the virus multiplies so rapidly is that it mutates into a different strain," Podell said, one that isn't dependent on the presence of the other PBMC cells.

This virus strain – MD-A – appears to be completely independent of any immune system interaction. "That means that any drugs intended to interfere with, or influence the immune system may have absolutely no effect on the astrocyte infection in the brain," Podell said.

The experiments with methamphetamine exposure to the cells were surprising to the researchers.

"We found that if you treat these astrocyte cell lines with methamphetamine at the time that they are infected with FIV, and if you continuously expose them to the drug, you can see as much as a 15-fold increase in viral replication," Podell said.

"You can basically take this cell that normally has a limited ability to consistantly replicate virus and just dramatically turn it on, simply by adding methamphetamine."

The research team is now analyzing data obtained from as series of experiments that used cats as an animal model. If the findings are corroborated in the animals, Podell and his colleagues will try to unravel the precise mechanisms that are controlling FIV infection in these cells.

"The most difficult issue lies ahead, and that is understanding what mechanism is occurring and potentially discovering how to stop or block viral infection and replication in this environment," he said.

The project was supported by grants from the National Institute on Drug Abuse and the National Institutes of Health.

Ecstasy Link To Long-Term Brain Damage

Disturbing evidence is emerging that the increasingly popular drug ecstasy can be linked to users suffering long-term brain damage.

University of Adelaide researchers have found that ecstasy taken on a few occasions could cause severe damage to brain cells, with the potential to cause future memory loss or psychological problems.

Dr Rod Irvine, an internationally regarded ecstasy expert from the University's Department of Clinical and Experimental Pharmacology, says with 7% of 17-year-olds reporting use of ecstasy, major health problems could be expected in the future.

"For many years it has been known from animal experiments that small doses of ecstasy-even if only taken on only a few occasions-can cause severe damage to certain brain cells," he says. "More recently, evidence has started to accumulate suggesting that this damage may also occur in humans. Brain scans and psychological assessment of ecstasy users has been used to obtain this information.

"If our suspicions are proved correct, it will mean many of our young people will have memory loss or psychological problems in the future."

Dr Irvine's research on brain damage caused by ecstasy shows that the drug seems to work mainly through its effects on one type of brain cell, and even through one molecule in those cells. It also seems likely that the way the body reacts chemically to ecstasy is important in producing adverse effects, as is the surrounding temperature, which can lead to users overheating.

Adelaide's reputation as having the highest per capita death rate from ecstasy in Australia-and perhaps even the world-forms another component of Dr Irvine's research.

Dr Irvine is looking at the shorter-term consequences of ecstasy "overdoses", and has established that the high rate of death is due to a different strain of ecstasy appearing on the Adelaide market in the mid1990s.

"Normal" ecstasy contains the pharmacological ingredient known as MDMA as its main ingredient, but the Adelaide strain often contained no MDMA but rather a more potent chemical known as PMA.

"PMA hasn't been around since the early 1970s when it was responsible for the deaths of several people in Ontario, Canada, and now it's reappeared here in Adelaide," Dr Irvine says. "We don't know where the PMA came from, but we do know that it has been prevalent in Adelaide since the mid 1990s."

Brain Shows Ability To Recover From Some Methamphetamine Damage

UPTON, NY — A new brain-imaging study at the U.S. Department of Energy's Brookhaven National Laboratory indicates that some of the damage caused by methamphetamine — a drug abused by ever-increasing numbers of Americans — can be reversed by prolonged abstinence from the drug. The results appear in the December 1, 2001 issue of The Journal of Neuroscience.

"Methamphetamine is a particularly problematic, highly addictive drug," said Nora Volkow, who led the study with Linda Chang. Their team had previously shown that methamphetamine abusers have significantly depleted levels of dopamine transporters. These proteins, found on the terminals of some brain cells, recycle dopamine, a brain chemical associated with pleasure and reward and also essential for movement. The study also found that meth abusers had impaired cognitive and motor function (see http://www.bnl.gov/bnlweb/pubaf/pr/bnlpr030101.htm).

"These changes could mean that meth abusers would be predisposed to such neurodegenera-tive disorders as Parkinson’s disease, which is also characterized by problems with dopamine and motor function," Volkow said. "It depends in part on whether the damage is reversible."

To help answer this question, Volkow and her team used positron emission tomography, or PET scanning, to measure the level of dopamine transporters in methamphetamine abusers after varying periods of abstinence. One group of 12 methamphetamine abusers was scanned within 6 months of taking the drug, and, for 5 of these subjects who managed to stay drug-free, the scan was repeated after 9 months of abstinence. Another group of 5 methamphetamine abusers was studied only after 9 months of abstinence. All subjects were compared with normal controls.

For each scan, each study volunteer was given an injection carrying a radiotracer, a radioactive chemical "tag" designed to bind to dopamine transporters in the brain. The researchers then scanned the subjects' brains using a PET camera, which picks up the radioactive signal of the tracer bound to the transporters. The strength of the signal indicates the number of transporters.

The scientists also looked for improvements in cognitive and motor function after abstinence by administering a battery of neuropsychological tests. These included tests of fine and gross motor function and tests of attention and memory.

The main finding was that, in methamphetamine abusers who were able to stay drug-free for at least 9 months, dopamine transporter levels showed significant improvement, approaching the level observed in control subjects. In abusers studied within 6 and after 9 months, the longer the period between the first and second evaluation, the larger the increase in dopamine transporter levels. Cognitive and motor function showed a trend toward improvement on some tests, but these changes were not statistically significant.

"The increase in dopamine transporter levels with prolonged abstinence indicates that the terminals of dopamine-secreting cells, which are thought to be damaged by methamphetamine abuse, are able to regenerate," Volkow said. Another possibility is that other, undamaged terminals are able to branch out and make up for the loss.

"These findings have implications for the treatment of methamphetamine abusers because they suggest that protracted abstinence and proper rehabilitation may reverse some of the meth-induced alterations in dopamine cells," Volkow said. "Unfortunately, we did not see a parallel improvement in function."

The recovery of dopamine transporters may not have been sufficient to completely make up for the damage to the dopamine terminals, she suggested. Additionally, other systems necessary for neuropsychological function might also be damaged by the drug — and less able to recover. Also, Volkow noted, the sample sizes were small. "Further study in larger samples is required to assess whether recovery of dopamine transporters with protracted abstinence is associated with recovery of neuropsychological function," she said.

This work was funded by the U.S. Department of Energy, which supports basic research in a variety of scientific fields; the National Institute on Drug Abuse; the National Institutes of Health; and the Office of National Drug Control Policy.

The U.S. Department of Energy's Brookhaven National Laboratory (http://www.bnl.gov) conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies. Brookhaven also builds and operates major facilities available to university, industrial, and government scientists. The Laboratory is managed by Brookhaven Science Associates, a limited liability company founded by Stony Brook University and Battelle, a nonprofit applied science and technology organization.

Ecstasy Component May Help Researchers Measure Brain Damage From The Drug

Researchers in Spain have isolated for the first time a by-product of the illicit drug Ecstasy that is believed to cause some of the brain damage associated with the drug. They believe their finding will help them measure, with greater precision, the long-term neurotoxicity of Ecstasy in human users.

The report will be published in the September issue of Chemical Research in Toxicology, a peer-reviewed journal of the American Chemical Society, the world’s largest scientific society.

The findings may corroborate speculation that HHMA (3,4 dihydroxymethamphetamine), is at least partially responsible for Ecstasy’s harm to the human brain, according to lead researcher Rafael de la Torre, D.Pharm., of the Municipal Institute of Medical Research in Barcelona. Previous study had linked HHMA to many of Ecstasy’s known side effects, but until now researchers had not been able to accurately measure the amounts of HHMA in users.

HHMA is created when Ecstasy (known chemically as MDMA, or 3,4- methylenedioxymethamphetamine) is metabolized through the liver. Animal studies have shown Ecstasy to damage the brain’s thought and memory function, but research has indicated that such side effects don’t develop until the drug is metabolized. Accurately measuring the amount and concentration of HHMA in a person’s body can provide new insight into the drug’s effects, including how it is metabolized, and possibly determine its long-term effects, de la Torre said. HHMA does not occur naturally in the body and thus would not be found in a non-user of Ecstasy, he noted.

“This observation concerns not only Ecstasy’s acute effects, but more interestingly, its mid- and long-term neurotoxicity,” de la Torre said. “The detection of HHMA was hampered up to now by problems measuring it in humans, which we have solved.”

The research represents the first validated method for measuring HHMA in body fluids, according to de la Torre. It involved four men who each volunteered to take a 100-milligram dose of Ecstasy and submit blood and urine samples regularly for the following 24 hours. All were described as regular users of the drug. The researchers found nearly identical concentrations of HHMA and MDMA in the samples, establishing HHMA as a likely contributor to conditions associated with Ecstasy use, de la Torre said.

In widespread use since the 1980s, Ecstasy is a stimulant with effects similar to the short-term euphoria and increased alertness claimed by cocaine users, according to the National Institute on Drug Abuse. It is considered dangerous, however, since it has been shown to damage nerve cells in the brain critical for thought and memory, NIDA reports. Other experiments show that people who take MDMA score lower on memory tests and that animals have persistent effects from the drug six to seven years after exposure.

The research cited above was funded by the Spanish government and the Spanish National Plan on Drugs in Madrid.

Rafael de la Torre, D. Pharm., is a researcher in the pharmacology research unit at the Municipal Institute of Medical Research in Barcelona and a professor of toxicology and pharmacology at the Autonomous University in Barcelona.

Mother's Drug Use Increases Risks For Male Offspring

Exposure before birth to methamphetamine, an increasingly popular "club" drug, renders males, even as adults, much more susceptible to the drug's brain-damaging effects, reveals a study performed in mice by researchers at the University of Chicago.

If males who were prenatally exposed to methamphetamine take the drug themselves as teens or adults, the increased toxicity could hasten the onset of brain disorders such as Parkinson's disease, warn the authors in the August issue of the Journal of Pharmacology and Experimental Therapeutics, published electronically on July 13.

"No one who values his or her brain should take this drug," cautions neurotoxicologist Alfred Heller, M.D., Ph.D., professor of neurobiology, pharmacology and physiology at the University of Chicago and director of the study. "If you're male, and if your mother took methamphetamine — and it's difficult to be certain she didn't — you should not go near this drug."

Methamphetamine — also known as "meth" or "chalk," or when smoked as "crystal," "crank" or "ice" — is the world's second most widely used illicit drug, according to the World Health Organization, and is rapidly gaining popularity. After claiming a foothold in the Southwest in the early 1990s, it has spread across much of the United States.

"We now are seeing high levels of methamphetamine abuse in many areas of the Midwest," notes an alert on the National Institute of Drug Abuse (NIDA) web site, "in both urban and rural settings, and by very diverse segments of the population."

Cheap, long-lasting, easy to make, easy to take and perceived as relatively safe, this stimulant is widely used by young women because it elevates mood, boosts energy, suppresses appetite and helps with weight loss.

Researchers have long known that methamphetamine has multiple side effects. It damages neurons that use the neurotransmitter dopamine to relay signals. Women who abuse the drug during pregnancy have increased risk of premature delivery. Their newborns are often unusually irritable. But because the drug has only recently become so popular, there is limited information about its long-term effects on users' offspring.

Last spring, recognition of methamphetamine's blossoming popularity among young women, and the uncertainty about its effects on an exposed fetus, provoked NIDA to call for research on how the drug affects brain development for those exposed in utero.

Heller's group at the University of Chicago had already developed a mouse model of prenatal methamphetamine exposure. They determined the dose that exposed the mouse fetal brain to similar concentrations of methamphetamine as in human infants and then studied its effects on the exposed mice and their offspring.

The key finding was that male mice who were exposed to the drug before birth and then exposed again as adults (at 11 weeks old), were significantly more vulnerable to methamphetamine's neurotoxic effects. These males suffered damage to the dopamine-using neurons, particularly in areas of the brain known as the substantia nigra and the striatum, the system that is damaged in Parkinson's disease.

Why the effect was so much greater in males than females is unclear. It may be connected with the rise in body temperature associated with use of the drug. The amount of brain damage was closely associated with this increase in body temperature in exposed mice. Methamphetamine increases core temperatures more in males than in females.

The researchers also suggest that a likely mechanism for the increase in brain damage is that fetal exposure to methamphetamine increases the release of dopamine from adult brain cells by methamphetamine.

When stimulated later in life by this drug, these preconditioned nerve cells release abnormal amounts of dopamine, which accumulates outside the cells, where it can be chemically altered or oxidized. Heat exacerbates this dopamine secretion. When the altered neurotransmitters are taken back up into these nerve cells, they can be toxic. In fact, drugs that block re-uptake can prevent this toxicity.

The enhanced neurotoxicity in response to methamphetamine in male animals exposed in utero "may be an additional risk factor in the development of parkinsonism," note the authors. "With age, the persistent damage to the dopaminergic system may predispose these individuals to brain disorders."

Although Parkinson's disease doesn't immediately appear in these animals, or in most human drug users, the drug may be setting the stage for early disease onset. People begin to exhibit symptoms, such as slowed movements, rigidity and tremors, only after losing more than 80 percent of the dopamine-producing cells in the substantia nigra.

"Regular methamphetamine users, or those at increased risk because of prenatal exposure, may have a head start on this process," suggests Heller.

Additional authors of the study include Nancy Bubula, Robert Lew and Lisa Won of the University of Chicago, and statistician Barbara Heller, from the Illinois Institute of Technology.