One Hit Of Crystal Meth Causes Birth Defects, Affects Fetuses At All Stages Of Development

A single prenatal dose of methamphetamine — commonly known as speed — may be enough to cause long-term neurodevelopmental problems in babies, say University of Toronto researchers.

In research published in the August issue of Free Radical Biology and Medicine, U of T pharmacy and pharmacology professor Peter Wells and his colleagues determined that exposing pregnant mice only once to methamphetamine led to delivery of offspring with long-term neurodevelopmental problems, including reduced motor co-ordination. Methamphetamine is a potent and addictive stimulant.

"We've known for a while that meth abuse during pregnancy is associated with low birth weight, cleft palates and other malformations but this is the first research demonstrating that even a single exposure can cause long-term damage," says Wells. "It's pretty remarkable that a single low dose can have such an effect.

"It's an important finding, given the increasing use of club drugs among women of childbearing age. It has clinical implications, because it shows that the fetus is exquisitely sensitive."

The developing fetus appears to be vulnerable to DNA damage from methamphetamine exposure because it hasn't yet developed the enzymes that protect it against free radicals — highly activated, destructive oxygen molecules that have been implicated in cancer and neurodegenerative diseases, says Wells. This vulnerability lasts from the embryonic stage through the later fetal period, times when organ structures and mental functions develop.

"People usually think the last trimester of pregnancy is when developing brain function is most susceptible to damage, but in this case the brain is also affected by methamphetamine even in the earlier embryonic period," says Wells.

Wells' next step will be to study women and their babies who have been exposed to drugs like methamphetamine that enhance free radical formation to see if the human damage is consistent with his mouse findings. He will also try to determine whether the methamphetamine causes other lasting damage in mice, such as impacts on learning and memory.

"Methamphetamine has very different toxic effects in the fetal brain than in adult mice, which surprised me," says Wells. "In adults, you can see actual structural degeneration of the brain."

U of T doctoral candidates Winnie Jeng and Andrea Wong and undergraduate Ryan Ting-A-Kee were also involved in this study. The research was supported by a grant from the Canadian Institutes of Health Research (CIHR). The doctoral candidates received awards from the CIHR/Rx&D Health Research Foundation, the American Society of Toxicology and the Natural Sciences and Engineering Research Council of Canada.

Brain Region Recovery Possible In Former Methamphetamine Users

CHICAGO — Adaptive changes in chemical activity in certain regions of the brain of former methamphetamine users who have not used the drug for a year or more suggest some recovery of neuronal structure and function, according to an article in the April issue of the Archives of General Psychiatry, one of the JAMA/Archives journals.

Methamphetamine use has been shown to cause abnormalities in brain regions associated with selective attention and regions associated with memory, according to background information in the article. Recent animal and human studies suggest that neuronal changes associated with long-term methamphetamine use may not be permanent but may partially recover with prolonged abstinence.

Thomas E. Nordahl, M.D., Ph.D., of the University of California, Davis, and colleagues compared eight methamphetamine users who had not used methamphetamine for one to five years and 16 recently abstinent methamphetamine users who had not used the drug for one to six months with 13 healthy, non-substance-using controls using a method of brain imaging, proton magnetic resonance spectroscopy (MRS), that allows the visualization of biochemical markers that are linked with damage and recovery to the neurons in the brain.

The researchers measured biomarkers in the anterior cingulum cortex, a region of the brain associated with selective attention. Levels of N-acetylaspartate (NAA), which is present only in neurons, were measured as a marker of the amount of damage (neuronal loss). Choline (Cho), which is generated by the creation of new membranes and, the authors write, "may be an ideal marker to track changes consistent with neuronal recovery associated with drug abstinence," was measured as a biomarker of recovery.

Levels of NAA were abnormally low in all the methamphetamine users, the authors found. Levels were lower relative to the length of methamphetamine use, but did not change relative to the amount of time that the methamphetamine users had been abstinent. The researchers found elevated Cho levels in the methamphetamine users who had not used the drug in one to six months, but normalized levels in the longer abstainers. "In the early periods following methamphetamine exposure, the brain may undergo several processes leading to increased membrane turnover. The relative Cho normalization across periods of abstinence suggests that when drug exposure is terminated, adaptive changes occur, which may contribute to some degree of normalization of neuronal structure and function," they write.

"The understanding of how the human brain can recover or partially recover as a function of extended drug abstinence has important implications both for the neurobiology of addiction and substance abuse treatment," the authors conclude. "Additional longitudinal studies…are needed to further understand the underlying physiological changes of stimulant drugs on the human brain."

(Arch Gen Psychiatry. 2005;62:444-452. Available post-embargo at archgenpsychiatry.com)

Editor's Note: This study was supported by grants from the National Institute on Drug Abuse, Bethesda, Md.

Chemists Identify Immune System Mechanism For Methamphetamine Binges

— SAN DIEGO, March 15 — Chemists at The Scripps Research Institute have found evidence in laboratory studies that the immune system may be able to recognize methamphetamine and boost tolerance to the drug through an unusual vaccine-like mechanism. Their finding, if confirmed in human studies, could help explain why chronic users go on long binges with the illicit drug, also known as speed. The study could lead to new treatments for the drug’s addiction, they say.

Recent studies by others have documented the drug’s apparent ability to suppress the immune system, making abusers more vulnerable to diseases such as HIV. The new study is the first to suggest that the drug can engage the body’s defense system to attack methamphetamine in such a way that makes users inclined to use more of the drug, the researchers say. Their study, which paints a clearer picture of the drug’s effect on the immune system and its potential for abuse, was described today at the 229th national meeting of the American Chemical Society, the world’s largest scientific society.

“Test animals injected with methamphetamine actually developed antibodies to the drug, which is highly unique for a molecule of its relatively small size,” says study co-leader Kim Janda, Ph.D., a chemist at Scripps in La Jolla, Calif. Developing antibodies to the body’s invaders, such as viruses and bacteria, is normally a good thing and forms the basis of modern vaccines, he explains. But ironically, people who abuse methamphetamine may build up antibodies to the drug itself, so they require increasing amounts to get high, resulting in binging behavior, he says.

“Without knowing it, they’re essentially vaccinating themselves against the drug, and that’s not a good thing as it requires more of the drug to get high,” says Janda. His findings were first reported in a recent issue of the Journal of the American Chemical Society, the Society’s peer-reviewed journal.

In a test tube study designed to simulate the chemical reactions that occur with the drug when it enters the bloodstream, the researchers showed that methamphetamine reacts with glucose and proteins to form a larger-size “glycated” product. This product is then recognized by immune system components, stimulating the production of antibodies to the drug. In follow-up studies using mice, those injected with the drug developed antibodies to it.

“Antibodies are usually produced only in response to large molecule invaders such as proteins, not to small drug molecules,” Janda says. “Glycation acts like a linker that allows [the methamphetamine] to be displayed to the immune system, triggering a vaccine-like reaction.”

Just as a vaccine is able to remove invading pathogens by using antibodies to the pathogen, antibodies to methamphetamine attack and begin to clear the drug, Janda says. If the antibodies prevent some of the drug from reaching its place of action in the brain’s pleasure center, users might require more of the drug because some of it is bound up by antibodies and “soaked up like a sponge,” according to the researcher.

“If the mechanism we proposed proves true in humans, then it will help explain why addicts go on prolonged binges, requiring more frequent intake and ever-increasing amounts of the drug in order to achieve a high,” says Janda, who led the study with his former student, Tobin Dickerson, Ph.D., also a chemist at Scripps.

Other drugs of abuse, including nicotine and ecstasy (which is structurally similar to methamphetamine), might share a similar mechanism of action involving immune system recognition and a consequent rise in tolerance to the drug, Janda and his associates theorize. Tolerance refers to the capacity to have a decreased response to a drug after prolonged use. Increased drug tolerance raises the likelihood that a person will become addicted.

“Right now, there’s nothing really effective in getting people off methamphetamine,” says Janda, who believes that highly specific methamphetamine antibodies can be made in a laboratory and then used as a clinical treatment for addiction. In theory, antibodies to the drug could be mass produced and administered at therapeutic levels that are high enough to clear the drug from the body, he says.

“Methamphetamine has become the ‘crack’ of the 21st century,” Janda says. “We’re just starting to unravel its mechanism of addiction.” Further studies of the drug are planned, he adds. Methamphetamine is a powerful psychostimulant that goes by a number of common names, including “speed,” “ice” and “crank.” It is often made in make-shift laboratories using over-the-counter drug ingredients, particularly cold and allergy medicines. Available as a powder or crystal, the drug can be injected, snorted, swallowed and smoked to provide users with a sense of euphoria. Drug effects can last for up to 12 hours. Frequent use is associated with serious health problems, including memory loss, aggression, psychotic behavior, and potential heart and brain damage.

The Skaggs Institute for Chemical Biology (at Scripps) and the National Institute on Drug Abuse provided funding for this study. In addition to Janda and Dickerson, other study co-authors include Noboru Yamamoto and Diana Ruiz, also of Scripps.

The American Chemical Society is a nonprofit organization, chartered by the U.S. Congress, with a multidisciplinary membership of more than 159,000 chemists and chemical engineers. It publishes numerous scientific journals and databases, convenes major research conferences and provides educational, science policy and career programs in chemistry. Its main offices are in Washington, D.C., and Columbus, Ohio.

Methamphetamine's Ruinous Effects On Children Documented In Midwest Study

— CHAMPAIGN, Ill. — In its destructive effect on rural families and their children, methamphetamine may be in a class of its own, based on the first study from an ongoing research project in seven Central Illinois counties, conducted by researchers at the University of Illinois at Urbana-Champaign.

If the children of alcoholics often find themselves in a “thunderstorm” of family problems, then the drug methamphetamine brings a “tornado” by comparison, says one of the researchers. The professionals and caregivers who pick up the pieces often lack the knowledge or resources to deal with the children’s trauma and its consequences, the study found.

“These kids are at a very high risk for mental health and substance-abuse disorders, and yet we have very little descriptive information about their psychological development and well-being,” said Wendy Haight, the Illinois social work professor who is leading the research.

Despite the spread of methamphetamine use since the late 1980s, and in Illinois for at least a decade, this study may be the first to look at the culture and family dynamics it creates, especially in rural areas, and the effect of that on the children of users, Haight said. “Even though our study is rooted in a particular community, it has wider implications in terms of how we approach this problem, looking at the unique rural context,” she said.

Everyone dealing with the problem, from social workers to teachers to police, “is grasping at straws,” according to Linda Kingery, a social work graduate student and one of the project researchers, as well as a child-welfare worker in the counties studied. Everyone is looking for answers, she said, “and that’s why this research is so relevant.”

The study found situations of profound neglect and abuse, physical danger resulting from in-house manufacture of the drug, and parents teaching their children criminal behavior and a paranoid distrust of authority.

The same rural isolation that makes it easier to hide the manufacture of the drug also makes it easier to hide evidence of child abuse and neglect, the researchers noted.

They heard stories of 10-year-old children becoming surrogate parents to younger siblings, as their parents went through days-long highs, often accompanied by psychotic symptoms, followed by crashes and days of sleep. Parents making the drug in their homes exposed their children to toxic fumes and the danger of explosions or fires. Some asked their children to steal items needed for making the drug or to stand guard, armed with a gun, looking out for police or other authorities.

One positive found in the research was the response of the community. “What we’ve seen is that in the rural community, the community steps up,” Kingery said. “When you have a small community, they know who’s doing what, and what these kids are going through, and the schools just constantly step up to the plate.”

Educators with suspicions about what is going on in a child’s family will make allowances for them staying after school, or providing for basic necessities, and the children often are eligible for free breakfast and lunch programs. “All of that may be completely up for grabs when they get home,” Haight said.

Haight and her research colleagues interviewed 35 people who had regular contact with children of methamphetamine-abusing parents, including 18 child-welfare workers, seven foster-caregivers, six counselors, a state’s attorney, a police officer, and an elementary school principal.

They also reviewed relevant local records and conducted about 90 hours of field work over six months, including 17 mornings or afternoons shadowing a child-welfare investigator on visits to rural homes. They also interviewed 12 children in foster care whose parents had abused methamphetamine.

The study was done in collaboration with the Charleston field office of the Illinois Department of Children and Family Services (DCFS), which covers the counties of Clark, Coles, Cumberland, Douglas, Edgar, Moultrie and Shelby.

The Charleston field office handles about 100 hotline reports of child maltreatment per month, and about a quarter involve parent methamphetamine abuse.

An article on their study, “In These Bleak Days: Parent Methamphetamine Abuse and Child Welfare in the Rural Midwest,” will be published in an upcoming issue of the journal Children and Youth Services Review.

Co-authors with Haight are Teresa Jacobsen, also a professor in the School of Social Work; James Black, a psychiatrist with Methodist Medical Center in Peoria and an adjunct professor in the university’s College of Medicine; Kingery, a child-welfare worker in the Charleston field office of DCFS; and Kathryn Sheridan and Cray Mulder, graduate students in social work.

Controversial Drug Shown To Act On Brain Protein To Cut Alcohol Use

 A naturally occurring hallucinogen advocated by some clinicians as a potent anti-addiction drug has been rigorously studied for the first time, confirming its ability to block alcohol craving in rodents, and clarifying how it works in the brain. The new research findings about the drug Ibogaine open the way for development of other drugs to reverse addiction without Ibogaine's side effects, potentially adding to the small arsenal of drugs that effectively combat addiction.

Derived from a West African shrub, Ibogaine has been championed for years by a cadre of clinicians and drug treatment advocates impressed with its ability to reverse withdrawal symptoms and craving for alcohol and various drugs of abuse. It has been used outside of the U.S. to treat addiction by American and other clinicians. But its side effects, including hallucinations, which made it popular in the 1960s drug culture, and evidence of toxicity to certain nerve cells in rodent studies have discouraged careful studies of its clinical potential against drug and alcohol addiction. The FDA has not approved use of Ibogaine in the U.S.

Scientists at UCSF's Ernest Gallo Clinic and Research Center have now shown definitively in experiments with mice and rats that Ibogaine does reduce alcohol consumption, and they have determined that it does so by increasing the level of a brain protein known as glial cell line-derived neurotrophic factor, or GDNF. In a separate study, they demonstrated that GDNF by itself decreases alcohol consumption.

The research is being published in the January 19 issue of The Journal of Neuroscience.

"By identifying the brain protein that Ibogaine regulates to reduce alcohol consumption in rats, we have established a link between GDNF and reversal of addiction — knowledge of a molecular mechanism that should allow development of a new class of drugs to treat addiction without Ibogaine's side effects," said Dorit Ron, PhD, UCSF associate professor of neurology and also principal investigator at the Gallo Center. Ron is co-senior author of the paper with Patricia Janak, PhD, UCSF assistant professor of neurology and also principal investigator at the Gallo Center.

In their research, the scientists first carried out classic behavioral studies showing that Ibogaine reduced alcohol consumption. They induced the rats to consume alcohol in daily drinking sessions and then demonstrated that their drinking declined precipitously when they received Ibogaine. The drug was administered either by injection or directly into the same brain region where GDNF levels were shown to increase.

The research also showed that Ibogaine was quite effective in preventing relapse, or "falling off the wagon" — the vulnerability of recovered alcoholics or addicts to return to uncontrolled drinking or drug use when exposed to the drug of abuse months or even years after breaking the habit.

In this analysis, the researchers provided alcohol to rats until they had become "experienced" daily drinkers. They then withheld alcohol for two weeks, which normally leads to greatly increased drinking when when alcohol is again available. When they administered Ibogaine, they found that the heightened craving and consumption was significantly reduced.

"The discovery that Ibogaine reduced binge drinking after a period of abstinence was an exciting finding for us because this is the type of behavior in alcoholics for which very few effective drugs exist," Janak said.

The scientists confirmed in a cell model that Ibogaine stimulated GDNF activity. Finally, they showed that a known inhibitor of GDNF blocked Ibogaine's ability to decrease alcohol craving in the rats, suggesting a direct link between Ibogaine's desirable actions and GDNF.

"If we can alter the GDNF pathway, we may well have a new treatment against alcohol and drug addiction without the unwanted side effects of Ibogaine," Ron said.

Colleagues in the research and coauthors on the paper are postdoctoral fellows Dao-Yao He, PhD, Nancy N.H. McGough, PhHD; Ajay Ravindranathan, PhD; Jerome Jeanblanc, PhD; Marian Logrip, BA, UCSF neurology graduate student; and Khanhky Phamluong, BA, research associate, all at the Gallo Center.

The research is supported by funds provided by the State of California through UCSF for medical research on alcohol and substance abuse, and by the Department of Defense.

Is It Ethical To Use Enhancement Technologies To Make Us Better Than Well?

— A variety of biomedical technologies are being developed that can be used for purposes other than treating disease. Such "enhancement technologies" can be used to improve our appearance and regulate our emotions, with the goal of feeling "better than well." While these technologies can help people adapt to their rapidly changing lifestyles, their use raises important ethical issues.

In a provocative debate in this month's PLoS Medicine, the premier open-access medical journal, two of America's foremost medical ethicists, Arthur Caplan and Carl Elliott, lay out the pros and cons respectively of these new enhancement technologies.

Caplan, who chairs the Department of Medical Ethics at the University of Pennsylvania School Of Medicine, says that "nobody is perfect–but why not try to be better?" He argues that it is in our human nature to strive for self-improvement and he sees real value in using technology to "enhance our vision, memory, learning skills, immunity, or metabolism." What's more, says Caplan, "putting the brakes on biologically driven human betterment would have real consequences for science. Some lines of research would be slowed or restricted." There is no reason why we "should not try to improve the biological design with which we are endowed."

But Elliot, Associate Professor at the Center for Bioethics at the University of Minnesota, and author of the book Better Than Well, worries "about the larger social effects of embracing medical enhancement technologies too enthusiastically." For example, athletes taking steroids may improve their own ability but they set off "a steroid arms race" that could destroy their sport. Manufacturers of enhancement technologies "will usually exploit the blurry line between enhancement and treatment in order to sell drugs." Citing the story of the diet drug Fen-Phen, Elliot says that "an alarming number of supposedly risk-free enhancements have later been associated with unanticipated side effects."

Proposed Addiction Treatment Successful, Safe In Second Small Trial

A second, small clinical trial of a proposed addiction treatment led by investigators at NYU School of Medicine and the U.S. Department of Energy's Brookhaven National Laboratory has produced favorable results in the treatment of long-term addiction to methamphetamine and/or cocaine, with no visual side effects in any of the 30 patients enrolled.

This latest research on GVG (gamma-vinyl GABA), led by Jonathan Brodie, M.D., Ph.D., the Marvin Stern Professor of Psychiatry at NYU School of Medicine and the study's lead author, and Stephen Dewey, Ph.D., of Brookhaven National Laboratory, was conducted at a national addiction treatment center in Mexicali, Mexico. The results are published in the February 2005 issue of Synapse, now available online.

"The fact that this drug appears to be effective in treating addiction to both cocaine and methamphetamine is particularly promising, given that methamphetamine abuse is one of the fastest growing drug problems in this country," said Dr. Brodie.

"We are unaware of any pharmacologic strategy that has been useful in treating methamphetamine dependence, making these findings with GVG unique both in terms of safety and efficacy," said Dr. Brodie. "We expect that the small clinical trials of GVG will lead to larger, placebo-controlled studies of this promising treatment."

Drs. Dewy and Brodie have conducted extensive brain-imaging and behavioral studies on animals showing that GVG attenuates and, in some cases, blocks neurological and behavioral changes associated with drug addiction. Last fall, Drs. Brodie and Dewey published results from the first small-scale human clinical trial of GVG to assess its effects on drug abusers, and showed that it can block cocaine craving in addicts.

GVG is approved for the treatment of epilepsy in many countries, including Mexico, but it is not approved for any indication in the United States in part because some epilepsy patients who have taken cumulative doses in excess of 1500 grams have experienced a reduction in their field of vision. The current study was designed to look for such visual side effects while testing the efficacy of a relatively low GVG dose.

In response to word-of-mouth and newspaper-ad recruitment, 30 patients enrolled in the study. All had abused methamphetamine and/or cocaine daily for a mean duration of 12 years. The experimental design was "open-label," that is, the subjects knew they were getting GVG, an experimental treatment for drug addiction.

Of the 30 volunteers, 18 stayed in the study for the nine-week duration. Of those, 16 were methamphetamine- and cocaine-free for more than four consecutive weeks while two continued using but in reduced amounts. Twelve of the 16 remained free of methamphetamine and cocaine through the end of the study. No subject, whether they completed the trial or not, developed defects in visual fields or acuity.

"Due to the open-label nature of this study and the lack of a control group, we cannot conclude that these subjects' ability to abstain from drug use was a direct result of being given GVG," said Dr. Dewey. "However, in a group of heavy users where none had stayed 'clean' for more than several consecutive days in the past year, it is remarkable that 16 of 30 avoided using these highly addictive drugs for approximately four consecutive weeks while on GVG," said Dr. Dewey.

"Of course, the conclusive demonstration of treatment efficacy can only be provided by an appropriately blinded randomized study, where some patients are given GVG and others a placebo, and neither the researchers nor the subjects know which is which until after the results are analyzed," noted Dr. Brodie.

With the lack of visual side effects observed for the doses used in this study – a factor that has been viewed as an impediment to getting GVG approved in the United States – the scientists hope to see a large-scale study conducted soon.

This research was funded by the Biochemical Psychiatry Fund at the NYU School of Medicine; Catalyst Pharmaceutical Partners (CPP) of Coral Gables, Florida; the National Institute on Drug Abuse; and the Office of Biological and Environmental Research within the U.S. Department of Energy's Office of Science.

In October 2002, CPP received an exclusive worldwide license from Brookhaven Science Associates, operator of Brookhaven Lab, for the use of GVG for its application in treating drug addiction.

Long Thought Inflexible, Personality Disorders Show Evidence Of Change

— Personality disorder symptoms are supposed to be stable, enduring, and persistent across the lifespan, however researchers at Binghamton University, State University of New York, and Harvard report evidence that such disabling psychiatric conditions are flexible and appreciable change over time is possible.

One of the cardinal assumptions in psychiatry and psychology has long been that individuals who have personality disorders will be the way they are for their lifetime and that treatment offers little real hope of change. In fact, the official diagnostic nomenclature used in modern psychiatry (the DSM-IV of the American Psychiatric Association), describes these disorders as "inflexible" and "stable over time." Results from a landmark longitudinal study, which has followed a large number of young adults over time, now call into question the assumption that personality disorders never change.

The Longitudinal Study of Personality Disorders, under the direction of Professor Mark F. Lenzenweger at Binghamton University, State University of New York, has recently discovered that individuals who have personality disorder symptoms will show significant declines in their symptoms with the passage of time. "On average, our subjects showed a decline of 1.4 personality disorder features per year," noted Lenzenweger.

What is particularly fascinating about this finding is that the change is not explained by exposure to conventional treatments or the presence of another form of mental disorder, such as anxiety, depression, or other illnesses. The subjects in the study were examined carefully for personality disorder features at three time points over a four year period and a complex statistical procedure known as growth curve analysis helped to detect the changes that were happening in the subjects. The nature of the study design helped to assure that any observed change in the personality disorder features was not due to artifacts or shortcomings that plague other studies.

Personality disorders are conditions that reflect serious disturbances in social and occupational functioning and the nature of the disturbance is part and parcel of a person's personality. The personality disorders do not represent episodic disturbances, unlike other forms of mental illness such as schizophrenia, bipolar illness, or major depression. They are relatively common among the public, with approximately 10% of the population affected (a fact also discovered previoulsy in Lenzenweger's laboratory), and they make up a large proportion of those individuals seen for treatment by practicing mental health professionals. "Although the disorders are common, with 1 in 10 people affected, the good news is that we now know the disorders can change with time," states Lenzenweger. The recent emergence of specialized treatments for the personality disorders coupled with these new findings creates new hope for those affected with the conditions.

Common personality disorders are borderline personality disorder, which is characterized by unstable personal relations as well as self-destructive and impulsive behavior. Narcissistic personality disorder is characterized by grandiose self-importance and disregard for others. There are ten well-defined personality disorders according to the American Psychiatric Association.

The report by Lenzenweger and his colleagues, Matthew Johnson (Binghamton University) and John B. Willett (Harvard), will appear in this month's Archives of General Psychiatry. The study was sponsored, in part, by the National Institute of Mental Health (NIMH).

Ecstasy Affects Memory, New International Study Shows

— People who take the recreational drug ecstasy risk impairing their memory, according to an international study which surveyed users in places including the USA, UK, other European countries and Australia.

The study, which also surveyed non-drug users, found that those who regularly took ecstasy suffered from mainly long-term memory difficulties, and that they were 23 per cent more likely to report problems with remembering things than non-users.

The British research team, led by the University of Newcastle upon Tyne, also questioned volunteers about their use of other recreational drugs. It found those who regularly used cannabis reported up to 20 per cent more memory problems than non-users. Their short-term memory was mainly affected.

Because evidence has shown ecstasy users are likely to use other drugs, including cannabis, the researchers say they are vulnerable to a myriad of memory afflictions which may represent a 'time bomb' of cognitive problems for later life.

Results of the study are published in the current edition of the Journal of Psychopharmacology.

Use of ecstasy, otherwise known as 3,4-methylenedioxymethamphetamine, or MDMA, is on the increase, with up to two million tablets being consumed every weekend in the UK.

Until now, little has been known about the impact of ecstasy and other drug use on everyday and long-term memory.

Researchers from the Universities of Newcastle upon Tyne, Northumbria, Westminster, Teesside and East London surveyed drug users via a web-based questionnaire.

Volunteers were posed questions about their everyday and long-term memory and asked to rank the probability of scenarios such as finding a television story difficult to follow and forgetting to pass a message onto somebody.

The research team based their findings on responses from 763 participants but they also looked closely at a sub-group of 81 'typical' ecstasy users who had taken the drug at least ten times.

As well as analysing volunteers' responses to the memory tests, the team recorded the number of mistakes made when filling in the questionnaire.

They found the group of 'typical users' reported their long-term memory to be 14 per cent worse than the 480 people who had never taken ecstasy and 23 per cent worse than the 242 non-drug users.

In addition, this group made 21 per cent more errors on the questionnaire form than non-ecstasy users and 29 per cent more mistakes than people who did not take drugs at all.

Lead researcher Dr. Jacqui Rodgers, of Newcastle University, said: "We all know of cases where people have suffered acutely from the use of ecstasy, such as the teenager Leah Betts, but relatively little is known about the more subtle effects on the increasing number of regular users worldwide.

"Users may think that ecstasy is fun and that it feels fairly harmless at the time. However, our results show slight but measurable impairments to memory as a result of use, which is worrying.

"It's equally concerning that we don't really know what the long-term effects of ecstasy use will be, as it is still a poorly understood drug. The results indicate that users are potentially creating a time bomb of potential cognitive difficulties in later life.

"The findings also suggest that ecstasy users who take cannabis are suffering from a 'double whammy' where both their long-term and short-term memory is being impaired."

Dr. Rodgers, of the School of Neurology, Neurobiology & Psychiatry, added that the results could inform drug therapy techniques: "The findings may help drug services in the UK and elsewhere to explain the potential consequences of use so that people can make an informed decision as to whether to take ecstasy or not."

The study also found no significant differences between results from male and female participants.

New Study Suggests Methamphetamine Withdrawal Is Associated With Brain Changes Similar To Those Seen In Depression And Anxiety

Results of a new study indicate that people who have recently stopped abusing the powerfully addictive drug methamphetamine may have brain abnormalities similar to those seen in people with mood disorders. The findings suggest practitioners could improve success rates for methamphetamine users receiving addiction treatment by also providing therapy for depression and anxiety in appropriate individuals. The study is published in the January 2004 issue of the journal Archives of General Psychiatry.

“Methamphetamine abuse is a grave problem that can lead to serious health conditions including brain damage, memory loss, psychotic-like behavior, heart damage, hepatitis, and HIV transmission,” says Dr. Nora D. Volkow, director of the National Institute on Drug Abuse (NIDA), National Institutes of Health, which funded the study. “Currently, no medication exists to treat abuse or addiction to amphetamines or amphetamine-like compounds; however, drug counselors and other health professionals have successfully used behavioral interventions to treat addiction. Treatment outcomes may improve if associated mental conditions are addressed concurrently with addiction.”

Dr. Edythe London and her colleagues at the University of California Los Angeles, the University of California Irvine, and NIDA’s Intramural Research Program used positron emission tomography — PET, a technology to image brain activity — to compare glucose metabolism in the brains of 17 methamphetamine abusers who had stopped using the drug 4–7 days before their participation in the study, and 18 nonabusers. The methamphetamine abusers averaged a 10-year history of drug abuse that included consuming an average of 4 grams of methamphetamine per week. They said they had used the drug at least 18 of the preceding 30 days.

All participants responded to questions about their drug use, and underwent a PET scan to measure how their brains used glucose while they performed an attention task. On the day of the scan, participants rated their symptoms of depression and anxiety. The methamphetamine abusers also rated their cravings for the drug within 48 hours of the scan. The scientists found that methamphetamine abusers reported higher ratings of depression and anxiety than nonabusers.

The PET scans showed that the two groups exhibited significant differences in glucose metabolism in specific brain regions. In methamphetamine abusers, glucose metabolism was lower in brain regions linked to depressive disorders, depressed mood, and sadness. It was higher in brain regions linked to anxiety and drug cravings.

“Improving our awareness of substance abuse as a condition that does not exist in isolation will contribute to more effective prevention and treatment interventions,” says Dr. Volkow.

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.