Category: Crystal Meth

Young adults who abuse amphetamines may be at greater risk of suffering a tear in the main artery leading from the heart, UT Southwestern Medical Center researchers have found.

In the study, published in the August issue of American Heart Journal, researchers examined medical records from nearly 31 million people between 18 and 49 years old hospitalized from 1995 to 2007 and found that amphetamine abuse was associated with a threefold increase in the odds of aortic dissection.

"Aortic dissection in young people is rare, but it frequently can lead to death," said Dr. Arthur Westover, assistant professor of psychiatry at UT Southwestern and the study's lead author. "Doctors should screen young adults with aortic dissection for amphetamine abuse in searching for a potential cause."

Individual case reports have suggested a link between aortic dissection and amphetamine abuse, but this is believed to be the first epidemiological study of a large group of people on the issue, Dr. Westover said.

The aorta stems from the heart and is the largest artery in the body. Dissection occurs when a tear develops in the inner layer of the aorta, allowing blood to separate, or dissect. The blood can eventually cause a rupture in the aortic wall, often resulting in death.

Amphetamines are stimulants that can be used to treat medical conditions such as attention-deficit disorder. They also are abused illegally as recreational drugs or performance enhancers. Researchers note that the abuse of amphetamines — including methamphetamines, or "meth" — significantly increased among hospitalized young adults from 1995 to 2007.

Amphetamines act on the body in similar ways as cocaine, which also is associated with adverse effects on the heart. Medically, amphetamines are known to increase blood pressure, and hypertension is a known trigger of aortic dissection.

Researchers also analyzed medical data for more than 49 million people 50 years or older from the same time period.

"We found that the frequency of aortic dissection is increasing in young adults but not older adults," Dr. Westover said. "It is not yet clear why."

Researchers noted that in California, Hawaii, Oregon and Washington state, the percentage of aortic dissection cases linked to amphetamine abuse among young adults during the study period was three times greater than the national figure.

"This illustrates that in areas where amphetamine abuse is more common, there are greater public health consequences," Dr. Westover said.

Dr. Westover's research previously has linked amphetamine abuse to stroke and heart attack.

"This adds to our growing understanding of the cardiovascular risks associated with abuse of amphetamines," said Dr. Paul Nakonezny, associate professor of clinical sciences and psychiatry at UT Southwestern and an author on the paper.

The study was funded by the National Institutes of Health.

The number of methamphetamine-related emergency room visits decreased significantly in the year following the implementation of Oregon's law prohibiting the sale of over-the-counter decongestant containing pseudoephedrine, according to Oregon Health & Science Emergency Department physician-researchers.

Their findings were presented June 5, at the annual meeting of the Society of Academic Emergency Medicine in Phoenix, Ariz.

"This is one of the first studies to suggest that limitation of supply of an illicit substance may be effective at decreasing its use as well as its associated medical problems," said Rob Hendrickson, M.D., principal investigator, medical toxicologist and an associate professor of emergency medicine in the OHSU School of Medicine. "Our research suggests that the state legislation limiting the supply of methamphetamine was associated with a decrease in methamphetamine use and, in particular, a decrease in medical problems related to methamphetamine."

Methamphetamine is an illegal drug of abuse typically produced through the chemical conversion of over-the-counter pseudoephedrine. In July 2006 Oregon became the first state to make over-the-counter medicines containing ephedrine, pseudoephedrine and phenylpropanolamine — key ingredients used in the illegal manufacture of meth — prescription-only drugs.

Following the law's implementation, Hendrickson and colleagues in the OHSU Emergency Department (ED) sought to determine whether the new legislation was an effective deterrent of methamphetamine use or methamphetamine-related disorders.

To conduct their research, the research team queried OHSU ED physicians to determine whether each individual patient visit to the ED was methamphetamine-related. The ED physicians were required to enter a response in the patient's electronic medical record prior to discharge. A database was kept and 38,417 patients were recorded. Of those patient encounters, 721 were deemed meth-related.

Following the one-year study, Feb. 5, 2006, to Feb. 5, 2007, the researchers found a 35 percent decrease in visits to the ED that were related to methamphetamine and a 29 percent decrease in patients who admitted to methamphetamine use. They also report that in the months prior to the law's enactment, they had an average of 18 methamphetamine-related Emergency Department visits per week in the OHSU ED. Post-legislation, that number fell to an average 11.3 per week.

"We are hoping to further explore if the decreases that we see in methamphetamine-related visits continue in the future and if further limitations of supply or other interventions affect ED visits," Hendrickson said.

Co-investigators on the study are Robert Cloutier, M.D., assistant professor of emergency medicine, and K. John McConnell, Ph.D., associate professor of emergency medicine, both of the OHSU School of Medicine.

 Crystal meth (methamphetamine) is a highly addictive drug that seduces victims by increasing self-esteem and sexual pleasure, and inducing euphoria. But once hooked, addicts find the habit hard to break.

Barbara Sorg from Washington State University, explains that amphetamines enhance memory. 'In addiction we talk about the "drug memory" as a "pathological memory." It is so potent as to not be easily forgotten,' she explains. As memory plays an important role in addiction, Sorg wondered whether it might be possible to find out more about the effects of meth on memory by looking at the effect it has on a humble mollusc: the pond snail Lymnaea stagnalis.

Lymnaea hold memories about when to breathe through their breathing tubes (pneumostomes) in a three neuron network, which is much simpler than the colossal circuits that hold our memories. Ken Lukowiak from University of Calgary, Canada, has been working on the mechanisms of memory formation in these snails for most of his career, so he and Sorg decided to team up to find out whether a dose of meth could improve the snails' memories in the way it does human memories. They publish their discovery that memories formed by snails under the influence of meth are harder to forget, which could help us to understand human addiction, on 28 May 2010 in The Journal of Experimental Biology.

First Sorg and her students had to discover whether a dose of meth could affect the snails' breathing behaviour. According to Lukowiak, the snails breathe through their skins when oxygen levels are high, but when oxygen levels drop the snails extend their pneumostomes above the water's surface to supplement the supply. As the drug easily crosses the snail's skin, the team immersed the snails in de-oxygenated pond water spiked with meth, and watched to see how it affected their breathing. The snails stopped raising their pnemostomes at 1 and 3.3·μmol·l-1 meth, so having found a dose that altered the snail's behaviour, the team began testing its effects on the mollusc's long term memory.

The team trained the snails to remember to keep their pneumostomes closed when oxygen levels were low by poking them with a stick every time they tried to open their pneumostomes. Giving the snails two training sessions separated by an hour, the team knew that the molluscs would hold the memory for over 24·h, but what would happen if they trained the snails in meth-laced water?

Testing the snails in de-oxygenated pond water 24 hours later, the team were surprised to see that the snails seemed to have no recollection of their training, popping their pneumostomes above the water's surface. Maybe meth did not affect the snails' memories. But then Lukowiak remembered: 'If you put snails in a novel context even though they have memory they respond as if they don't have memory,' he says. Without meth in the water, the snails were ignoring their memory. However, when the team reintroduced meth to the test water, the snails suddenly remembered to keep their pneumostomes closed. This could explain why it's so hard for human addicts to kick the habit when returning to old haunts that trigger the addiction memory.

Next the team wondered whether meth could improve the snails' memories. First they immersed the snails in meth-laced pond water, then they moved them into regular de-oxygented pond water and gave them a training session that the snails should only recall for a few hours. In theory the snails should have forgotten their training 24 hours later, but would the meth improve the snails' memories so they remembered to keep their pneomostomes closed a day later? It did. A dose of meth prior to training had improved the snails' memories, allowing them to recall a lesson that they should have already forgotten. And when the team tested whether they could mask the meth memory with another memory, they found that the meth memory was much stronger and harder to mask.

So memories formed under the influence of meth seem to be harder to forget, possibly because the drug disrupts the mechanisms for forgetting, and could help us to understand how amphetamines enhance memory in humans.

Journal Reference:

1. Kennedy, C. D., Houmes, S. W., Wyrick, K. L., Kammerzell, S. M., Lukowiak, K. and Sorg, B. A. Methamphetamine enhances memory of operantly conditioned respiratory behavior in the snail Lymnaea stagnalis. Journal of Experimental Biology, 2010; 213: 2055-2065

 Children whose mothers abused methamphetamine (meth) during pregnancy show brain abnormalities that may be more severe than that of children exposed to alcohol prenatally, according to a study in the March 17 issue of The Journal of Neuroscience. While researchers have long known that drug abuse during pregnancy can alter fetal brain development, this finding shows the potential impact of meth. Identifying vulnerable brain structures may help predict particular learning and behavioral problems in meth-exposed children.

"We know that alcohol exposure is toxic to the developing fetus and can result in lifelong brain, cognitive, and behavioral problems," said Elizabeth Sowell, PhD, of the University of California, Los Angeles, who led the research team. "In this study, we show that the effects of prenatal meth exposure, or the combination of meth and alcohol exposure, may actually be worse. Our findings stress the importance of drug abuse treatment for pregnant women," Sowell said. A structure called the caudate nucleus, which is important for learning and memory, motor control, and motivation, was one of the regions more reduced by meth than alcohol exposure.

Of the more than 16 million Americans over the age of 12 who have used meth, about 19,000 are pregnant women, according to data from the National Surveys on Drug Use and Health. About half of women who say they used meth during pregnancy also used alcohol, so isolating the effects of meth on the developing brain is difficult.

Sowell's team evaluated the specific effects of prenatal meth-exposure by comparing brain scans of 61 children: 21 with prenatal meth and alcohol exposure, 13 with heavy alcohol exposure only, and 27 unexposed. Structural magnetic resonance imaging (MRI) showed that the sizes and shapes of certain brain structures varied depending on prenatal drug exposure.

Previous studies have shown that certain brain structures are smaller in alcohol-exposed children. In this study, the authors found these brain regions in meth-exposed children were similar to the alcohol-exposed children, and in some areas were smaller still. Some brain regions were larger than normal. An abnormal volume increase was noted in meth-exposed children in a region called the cingulate cortex, which is associated with control and conflict resolution.

The researchers were also able to predict a child's past exposure to drugs based on brain images and IQ information. Detailed data about vulnerable brain structures may eventually be used to diagnose children with cognitive or behavioral problems but without well-documented histories of drug exposure. Christian Beaulieu, PhD, of the University of Alberta in Canada, who was unaffiliated with the study, said this finding will help researchers understand which brain areas are most sensitive to injury during development.

"Ultimately, the goal would be to come up with strategies to first, minimize brain damage in the womb, and second, to improve the child's cognitive performance," Beaulieu said.

The research was supported by the National Institute of Drug Abuse, the National Institute of Alcoholism and Alcohol Abuse, and the March of Dimes. Additional support was provided by the National Center on Research Resources, the General Clinical Research Center, the National Institutes of Health through the NIH Roadmap for Medical Research, and the Center for Computational Biology.

Sarah Steele and Langtian "Ren" Yuan were both self-admittedly inexperienced Duke freshmen in the spring of 2006. But then they followed helpful directions of an assistant chemistry professor, added their own patience and ingenuity, and ended up identifying compounds that might allay the powerful cravings of methamphetamine and cocaine addiction.

The two women, now seniors, have since moved on to other things. But their earlier accomplishment was recently celebrated by a research paper in a British journal. It also helped bring the professor, Jiyong Hong, a $390,000 stimulus grant from the National Institutes of Health and the American Recovery and Investment Act to do follow-up research.

"I think this is a kind of showcase for something that Duke is very strong in — undergraduate research," Hong said. "And, socioeconomically, it deals with drugs of abuse that are huge problems."

Hong, whose research group investigates the synthesis of natural products for drug design as well as small molecules' roles in biological processes, got interested in finding small molecules that could inhibit the good feelings induced by meth and coke after reading a 2006 paper in the journal Science.

That study implicated a derivative of an enzyme called protein kinase C zeta (abbreviated PKCzeta) in brain chemistry changes involved in memory and learning.

"When people take methamphetamines and cocaine, that gets engraved in their memories," Hong said. "So the hypothesis was that by inhibiting a specific enzyme, in this case PKCzeta, we might be able to delete those memories."

The problem was that researchers had never identified a PKCzeta inhibitor, he added. "PKCzeta is one of the least studied members of the PKC family." In other words, his quest would be like searching for needles in a haystack.

Enter the two undergraduates. Steele, an intended biology major, showed up in Hong's lab to do an independent study tied to a freshman chemistry research seminar class. "I hadn't taken organic chemistry, but he explained everything to me so I was sure of what I was doing," she said.

Following Hong's elaborate instructions, Steele began the task of canvassing about 1,200 different small molecules looking for candidate PKCzeta blockers. "It was repetitive work, but once we learned the concept it was easy to continue," she recalled.

The work involved placing each candidate inhibitor into one of 96 tiny wells on a sample plate, along with PKCzeta and an energy-providing chemical called adenosine triphosphate (ATP), plus a light-emitting enzyme called luciferase.

If a candidate compound was ineffectual, then the ATP in the well would be used by PKCzeta's activity. But if a compound did interfere with the PKCzeta, then the energy of the ATP would instead cause the luciferase to light up. The better the blocking action, the brighter the glow.

Yuan, originally a premed student planning to triple major in biomedical engineering, economics and public policy, had also approached Hong seeking freshman work as a lab assistant, though not as part of a class.

"Originally I was asked to try to find an inhibitor for something other than PKCzeta," she said. But when Steele entered a different summer research program after the spring semester, "I kind of picked up where Sarah stopped.

"I was doing similar things as she, but really trying to pinpoint which specific compounds worked as inhibitors," Yuan recalled. "We were almost out of molecules to test by then. But, in the last batch, there were a series that were similar that all lit up really well."

The work required lots of transferring chemicals with the aid of a pipette, and then incubating them at different temperatures and at different concentrations. "That was a lot of hours," she said. "I was working almost full time during the summer. But I'm glad it paid off."

Other researchers from Duke's Chemistry Department and Medical Center, as well as a separate group from Korea, filled in gaps in the research. Their results were published online on May 8, 2009 in Molecular Biosystems, a journal of the Royal Society of Chemistry. That paper identified several promising PKCzeta blockers for further follow-ups that are now underway.

"I didn't expect to have anything come out of it," said Steele, who was listed as a coauthor. "But it's nice that something good did." Yuan was listed as the paper's first author. "Honestly, I think I got too much credit," she said. "But it was exciting."

Support for the study came from the National Institutes of Health, Duke and Korea's Ministry of Education, Science and Technology.

After her spring with Hong's lab, Steele went on to join another Duke research program that has been probing the relationship between nerve cells and immunity in roundworms, which led to her co-authoring a paper in the October 17, 2008 issue of the journal Science. She followed that up with summer cancer research in her native Tampa, Fla., and is now applying to medical schools.

Meanwhile, Yuan went on another pathway. After creating an experimental computer animation to help psychiatric patients take their medications on time, she dropped her premed plans, her major in biomedical engineering and her minor in political science to concentrate on economics and public policy.

"I would have kept up with all my majors and minors but it was just too stressful," she said. "I was overloading everything, staying up until 3 a.m. every single night." Her parents were "shocked," she acknowledged. "My dad's a doctor, my mom's a nurse and my aunts are all doctors too. It was the biggest decision of my life."

But now she is expecting to be first author on a paper from her public policy internship, "Managing Climate's Impact on Health: Common Ground for U.S. China Collaboration." Yuan has also discovered a liking for economics. With her fluency in Mandarin Chinese, French and English, she's hoping to work as a consultant, perhaps at a think tank.

NewsPsychology (Dec. 21, 2009) — Fruit flies may seem like unlikely heroes in the battle against drug abuse, but new research suggests that these insects — already used to study dozens of human disease — could claim that role. Scientists are reporting that fruit flies can be used as a simpler and more convenient animal model for studying the effects of cocaine and other drugs of abuse on the brain.

Their study appears online in ACS Chemical Neuroscience, a new monthly journal.

Andrew Ewing and colleagues note that laboratory mice, rats, and monkeys have been mainstays in research with the ultimate goal of finding effective medicines for treating addiction. Although these mammals have helped establish the behavioral effects of cocaine on the body, they provide relatively complicated models to study the effects of cocaine and other illicit drugs on the brain and nerves. In the hope for a new simpler animal model they turned to fruit flies, which have many biological similarities to mammals, but are easier to study.

The scientists confirmed those hopes in research that involved giving cocaine, amphetamine, methamphetamine, and methylphenidate to fruit flies and then studying brain chemistry with a microelectrode one-twentieth the diameter of a human hair. The results demonstrate that fruit flies are a valid model for studying drug addiction in humans, the scientists say.

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The above story is reprinted (with editorial adaptations by newsPsychology staff) from materials provided by American Chemical Society, via EurekAlert!, a service of AAAS.

Journal Reference:

1. Makos et al. Using in Vivo Electrochemistry To Study the Physiological Effects of Cocaine and Other Stimulants on the Drosophila melanogaster Dopamine Transporter. ACS Chemical Neuroscience, 2009; 091026104139091 DOI: 10.1021/cn900017w

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.

A team of researchers has mapped patterns of illicit drug use across the state of Oregon using a method of sampling municipal wastewater before it is treated.

Their findings provide a one-day snapshot of drug excretion that can be used to better understand patterns of drug use in multiple municipalities over time. Municipal water treatment facilities across Oregon volunteered for the study to help further the development of this methodology as a proactive tool for health officials.

Applying analytical methods advanced at Oregon State University, researchers from the University of Washington, McGill University and OSU collected single-day samples from 96 municipalities across Oregon and tested the samples for evidence of methamphetamine, cocaine, and "ecstasy" or MDMA.

The study, published this week in the journal Addiction, reports a demonstration of this methodology conducted by UW drug epidemiologist Caleb Banta-Green, OSU chemist Jennifer Field, OSU toxicologist Daniel Sudakin, McGill spatial epidemiologist Luc de Montigny, OSU faculty research assistant Laura Power and OSU graduate student Aurea Chiaia.

"This work is the first to demonstrate the use of wastewater samples for spatial analyses, a relatively simple and cost-effective approach to measuring community drug use," said Banta-Green, lead author of the paper. "Current measures of the true prevalence of drug use are severely limited both by cost and methodological issues. We believe these data have great utility as a population measure of drug use and provide further evidence of the validity of this methodology."

"Municipalities across the state generously volunteered to help us test our methods by collecting samples more or less simultaneously, providing us with 24-hour composite influent samples from one day — March 4, 2008," said Field, who led the laboratory analyses of the samples.

Using these samples from 96 municipalities, representing 65 percent of Oregon's population, the researchers calculated the presence, measured as index loads, of three stimulant drugs: methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA, or ecstasy), and benzoylecgonine (BZE, a cocaine metabolite).

They found that the index loads of BZE were significantly higher in urban areas and below the level of detection in some rural areas. Methamphetamine was present in all municipalities, rural and urban. MDMA was at quantifiable levels in less than half of the communities, with a significant trend toward higher index loads in more urban areas.

Researchers said the study validates wastewater drug testing methodology that could serve as a tool for public health officials. Officials could, for example, use the methodology to identify patterns of drug abuse across multiple municipalities over time.

The research team underscored, too, that data used for this study are inadequate as a complete measure of drug excretion for a community or entire state. The team looked at a single day, mid-week sample, for instance. Results might be altered depending on the day or time of year the sample was gathered.

"We believe this methodology can dramatically improve measurement of the true level and distribution of a range of illicit drugs. By measuring a community's drug index load, public health officials will have information applicable to a much larger proportion of the total population than existing measures can provide," said Banta-Green.

Currently, Field and Banta-Green are working on a project funded by the National Institutes of Health to determine the best method for collecting data in order to get a reliable annual estimate of drug excretion for a community.

— In a study published online by the Journal of Substance Abuse Treatment, UC Davis researchers report that it takes at least a year for former methamphetamine users to regain impulse control. The results tell recovering substance abusers, their families and drug-treatment specialists that it can take an extended period of time for the brain functions critical to recovery to improve.

"Recovery from meth abuse does not happen overnight," said Ruth Salo, lead author of the study and a UC Davis assistant professor of psychiatry and behavioral sciences. "It may take a year — or even longer — for cognitive processes such as impulse control and attentional focus to improve. Treatment programs need to consider this when monitoring recovering addicts' progress during their early periods of abstinence."

Salo specializes in the behavioral, neuropsychiatric and cognitive outcomes of methamphetamine addiction — a particularly difficult condition to treat, primarily due to prolonged, intense cravings for the drug. During her career, she has worked with hundreds of methamphetamine addicts.

"All of them want to know if there is hope," Salo said. "We used to think most, if not all, effects of meth addiction were permanent. This study adds to the growing evidence that this assumption is not true. I can confidently tell patients that the longer they stay in a structured rehabilitation program and remain drug free, the more likely it is that they will recover some important brain functions."

For the current study, Salo used the widely-validated, computer-based Stroop attention test to measure the abilities of 65 recovering methamphetamine abusers to use cognitive control — or direct their attention to specific tasks while ignoring distractors. Study participants had been abstinent for a minimum of three weeks and a maximum of 10 years, and they had previously used the drug for periods ranging from 24 months to 28 years. The data for the 65 individuals were compared to Stroop attention test data from 33 participants who had never used methamphetamine.

"The test taps into something people do in everyday life: make choices in the face of conflicting impulses that can promote a strong but detrimental tendency," Salo explained. "For meth users, impairments in this decision-making ability might make them more likely to spend a paycheck on the immediate satisfaction of getting high rather than on the longer-term satisfaction gained by paying rent or buying groceries."

The study analyzed cognitive control in terms of the amount of time since methamphetamine was last used as well as total time spent using the drug. The researchers found that those who were recently abstinent (three weeks to six months) performed significantly worse on the Stroop test than those who had been abstinent one year or longer. In addition, there was no statistical difference between test results for those abstinent at least one year and non-drug using controls. Longer-term methamphetamine use was associated with worse test scores. Similarly, longer-term abstinence was connected to improved test performance.

According to Salo, the new study mirrors previous magnetic resonance imaging (MRI) studies she and her colleagues published in 2005 showing a partial normalization of chemicals in selected brain regions after one year of methamphetamine abstinence.

"Together, the studies provide strong evidence that, eventually, meth abusers in recovery may be able to make better decisions and regain the impulse control that was lost during their drug use period," she said.

Salo said that more research is needed to determine just how the brain recovers from methamphetamine addiction and if behavioral treatments can hasten that recovery. She plans to continue neuroimaging studies to further define the brain functions affected by the drug. Her ultimate goal is to provide information essential to refining treatment programs for this population of drug users.

"Meth use worldwide is pandemic," she said, referring to the estimated 35 million people who have used the neurotoxic stimulant or similar drugs. "Recovery is difficult, but possible. The point of my research is to better understand the neural and behavioral consequences of this toxic drug along with the brain and behavior changes that are possible with long-term abstinence."

Other authors of "Drug Abstinence and Cognitive Control in Methamphetamine-dependent Individuals" include Thomas Nordahl, Martin Leamon and Charles Moore of UC Davis; and Gantt Galloway and Christy Waters of St. Luke's Hospital in San Francisco. Moore is also affiliated with the Kaiser Chemical Dependence Recovery Program in Sacramento.

The research was supported by grants from the National Institute on Drug Abuse.

Regular exercise can prevent the disruption of the blood brain barrier that normally occurs with a dose of methamphetamine comparable to that used by heavy meth users.

A University of Kentucky study is the first to look at the protective effects of exercise on the vascular effects of methamphetamine, effects that have been found clinically to contribute to serious, lasting, and sometimes fatal cardiovascular and neurological problems. Results of the study, conducted in young male mice, were reported April 22 at the Experimental Biology 2009 meeting in New Orleans. The presentation was part of the scientific program of The American Physiological Society.

Principal investigator Dr. Michal Toborek says the level of the protective effects of exercise on the integrity of the blood brain barrier after the human equivalent of one gram of methamphetamine was surprising even to the research team.

The results provide new understanding of the mechanisms through which the brain reacts to methamphetamine, particularly those related to oxidative stress. Results also suggest why exercise might help delay the onset of neurodegenerative diseases such as Alzheimer's and Parkinson's in which leakiness of the blood brain barrier is a characteristic.

The researchers placed 25 young male mice – aged three months, equivalent to the 20s in humans — in cages where they had access to exercise wheels. For five weeks, the animals took advantage of the wheels to run continually. Another 25 young mice were housed in similar cages but without access to wheels.

At the end of this "endurance exercise training" period, all mice were injected with 10 mg. of methamphetamine over a 24-hour period. All the mice displayed some of the same effects of meth as seen in humans: they appeared agitated and increased their physical activity, and their body temperature rose. But in terms of what was happening in the capillaries of the brain, there was a marked difference between the mice who had been exercising extensively for the previous five weeks and those who had been sedentary.

In the sedentary group of mice, the small capillaries in the brain experienced increased oxidative stress, causing the blood brain barrier to become more permeable. Toxins and inflammatory cells previously prevented from crossing the blood brain barrier then had access to the brain. The exercise group showed no such changes.

Changes in the blood brain barrier, especially the role of oxidative reactions, have been little studied in the past, says Dr. Toborek; the University of Kentucky study is the first to observe that meth administration produced an upregulation of NADPH oxidase, a major enzyme that causes oxidative stress.

This is a significant finding, says Dr. Toborek, because it delineates a mechanism for how meth causes oxidative stress. It also was significant that the exercise mice were markedly protected from such upregulation and consequently from the oxidative stress that weakened the capillaries in the brains of the non-exercise mice.

Exercise by no means protects against all the harmful effects of meth use, says Dr. Toborek, and the team now plans to study the effects and mechanisms involved in chronic meth abuse. However, he says, this study adds to the growing amount of data showing the positive and protective health effects of consistent exercise.

A physician by training, Dr. Toborek is a professor in the Department of Neurosurgery with joint appointments in molecular biochemistry and nutrition. Co-authors on the study are postdoctoral fellows Dr. Melissa Seelbach, Dr. Yean Jung Choi, and Dr. Lei Chen and research associate Dr. Andras Ibolya, all in Neurosurgery; Dr. Bernhard Henning, College of Agriculture; and Dr. Karyn Esser, physiology. The research was supported by the National Institute of Mental Health, NIH and the University of Kentucky Center for Muscle Biology.

— A first of its kind study examining the effects of methamphetamine use during pregnancy has found the drug appears to cause abnormal brain development in children. 

"Methamphetamine use is an increasing problem among women of childbearing age, leading to an increasing number of children with prenatal meth exposure," said study author Linda Chang, MD, with the John A. Burns School of Medicine, University of Hawaii at Manoa in Honolulu. "But until now, the effects of prenatal meth exposure on the developing brain of a child were little known."

For the study, brain scans were performed on 29 three and four-year-old children whose mothers used meth while pregnant and 37 unexposed children of the same ages. The MRI scans used diffusion tensor imaging to help measure the diffusion of molecules in a child's brain, which can indicate abnormal microscopic brain structures that might reflect abnormal brain development.

The scans showed that children with prenatal meth exposure had differences in the white matter structure and maturation of their brains compared to unexposed children. The children with prenatal meth exposure had up to four percent lower diffusion of molecules in the white matter of their brains.

"Our findings suggest prenatal meth exposure accelerates brain development in an abnormal pattern," said Chang. "Such abnormal brain development may explain why some children with prenatal meth exposure reach developmental milestones later than others."

Studies have shown that prenatal meth exposure can lead to increased stress and lethargy and poorer quality of movement for infants.

"While we don't know how prenatal meth exposure may lead to lower brain diffusion, less diffusion of molecules in white matter typically reflects more compact axonal fibers in the brain," said Chang. "This is consistent with our prior findings of smaller subcortical structures in children with prenatal meth exposure, which is the portion of the brain immediately below the cerebral cortex."

Long-term studies are underway to determine if the brain differences found in children with prenatal exposure to meth will normalize with age.

The research is published in the April 15, 2009, online issue of Neurology. The study was supported by the National Institute on Drug Abuse, the National Center for Research Resources, the National Institute of Neurological Disorders and Stroke and the Office of National Drug Control Policy.