Research News

Teen Drug Use Associated with Psychiatric Disorders Later in Life

Children who start to use alcohol, marijuana or other illicit drugs in their early teen years are more likely to experience psychiatric disorders, especially depression, in their late 20s. Although teens who started smoking at an early age were at increased risk for alcohol dependence and substance use disorders in their late 20s, they did not appear to be at an increased risk for depression or other psychiatric disorders. However, initiating tobacco use in late adolescence was associated with depression and other psychiatric disorders in the late
20s.

These findings are based on a 22-year study that tracked the self-reported substance abuse and health histories of 736 youths through their early-and mid-teen years into early adulthood. Scientists from the Mount Sinai School of Medicine and Columbia University started collecting data on the children in 1975, when the subjects were one through 10 years of age. Four follow-up interviews were conducted: in 1983, 1986, 1992, and 1997, when the average ages of the subjects were 14, 16, 22, and 27 years.

During mid to late adolescence, 18.8 percent of the subjects reported moderate to heavy tobacco use; 6.2 percent reported moderate to heavy alcohol use; 17.6 percent reported moderate to heavy marijuana use; and 3.4 percent reported moderate to heavy use of other illicit drugs. During young adulthood, these percentages increased to 35.4, 13.0, 18.4, and 3.7, respectively.

In 1997, when the subjects were in their late 20s, 8.3 percent qualified for a diagnosis of a major depressive disorder (MDD), 5.2 percent were alcohol dependent, and 6.1 percent had a substance use disorder. Heavy alcohol, marijuana, and other illicit drug use were significantly related to later psychiatric disorders. About 85 percent of the individuals diagnosed with MDD in their late 20s had used marijuana when they were younger and more than 66 percent had a prior history of alcohol and/or other illicit drug use.

• WHAT IT MEANS: This study adds to the growing body of knowledge about the complex relationship between drug abuse and psychiatric disorders. Such findings will be useful in efforts to develop more effective prevention and treatment interventions for individuals at risk for these co-occurring conditions.
  
  

Dr. David Brook and colleagues published the study, which was supported by the National Institute on Drug Abuse, in the November, 2002 issue of the Archives of General Psychiatry.

Study Finds Cocaine Use in Rats Affects Adolescents Differently than Adults

Many people who use drugs start during adolescence, a time when the brain is undergoing many neural changes. Now, researchers from the University of Miami School of Medicine have demonstrated in rats that repeated exposure to cocaine during adolescence may cause different neurochemical and behavioral effects than when exposure occurs during adulthood.

To study the behavioral effects of cocaine, Drs. Stephanie Collins and Sari Izenwasser administered either cocaine or a placebo to 12 adolescent rats and 16 adult rats daily for seven
days. Each day, the rats were placed in an enclosure with a photobeam array that recorded their activity. After 10 days during which the rats did not receive any substance, all of the rats were given cocaine and their activity was recorded.

Adult rats receiving cocaine for seven days showed a significantly higher daily increase in activity than the adult
group receiving the placebo. Ten days after cocaine administration stopped, the activity level of cocaine-exposed adult rats was greater when re-exposed to the drug than when they were initially exposed, indicating that they had developed a sensitivity to the behavioral effects of the drug.

Like cocaine-exposed adult rats, adolescent rats receiving cocaine had higher activity levels than the placebo
group. However, in contrast to the activity level of adult rats, the increase in activity level of adolescent rats receiving cocaine remained stable during the seven days of cocaine treatment. Further, the increase in activity after cocaine exposure 10 days later was no different than after their first exposure to the drug.

In a separate experiment to investigate the neurochemical effects of cocaine, either cocaine or placebo was administered to eight adolescent and eight adult rats daily for seven days. Ten days later, their brains were examined for changes in dopamine and serotonin receptors and transporters in the caudate putamen and the nucleus accumbens regions of the striatum.

Compared with adult rats in the placebo group, adult rats treated with cocaine showed significant increases in
dopamine transporter density in the caudate putamen. Serotonin transporter densities also were increased in the
caudate putamen and the nucleus accumbens. Adolescent rats showed no changes in dopamine or serotonin
transporter densities in either region.

• WHAT IT MEANS: Different behavioral and neurochemical adaptations to repeated cocaine administration maybe related to development factors and have implications for future directions in prevention and treatment interventions.
  
  

This study, funded by the National Institute on Drug Abuse, is published in the September 20, 2002 issue of Developmental Brain Research.

Scientists Identify Brain Regions Where Nicotine Affects Attention and Other Cognitive Skills

Nicotine administration in humans is known to sharpen attention and to slightly enhance memory. Now scientists, using functional magnetic resonance imaging (MRI), have identified those areas of the brain where nicotine exerts its effects on cognitive skills.

Their findings suggest that nicotine improves attention in smokers by enhancing activation in the posterior cortical and subcortical regions of the brain—areas traditionally associated with visual attention, arousal, and motor activation. This study provides the first evidence that nicotine-induced enhancement of parietal cortex activation is associated with improved attention.

The investigators used functional MRI to visualize nicotine’s effects on the brain during a rapid visual informationprocessing (RVIP) task -- a task that requires sustained attention and working memory. Fifteen smokers with and without a 21- mg transdermal nicotine patch performed the RVIP task while undergoing MRI screening. The subjects performed the RVIP task twice—once with a placebo patch and once with a nicotine patch—and were scanned during each session. They smoked their last cigarette 15 minutes before performing the RVIP task.

When smokers were given a placebo patch for the first scan and a nicotine patch for the second scan, there was improvement in task performance between the two scans. When smokers were given a nicotine patch for the first scan and a placebo patch for the second scan, there was no difference in their performance, suggesting that nicotine and practice interact.

Study findings also suggest that nicotine helps focus attention on task demands by shifting cognitive resources
from less “used” parts of the brain to regions required for task performance.

• WHAT IT MEANS: This study adds to the understanding of the effects of nicotine on the brain. Such understanding helps explain both nicotine’s addictive properties and potential therapeutic applications.
  
  

Dr. Elliot A. Stein, Neuroimaging Research Branch, Intramural Research Program, NIDA, and colleagues from the Medical College of Wisconsin and the Institute of Psychiatry in London published the study in the October 24, 2002 issue of Neuron.

Sigma Receptors Play Role in Mediating the Behavioral and Toxic Effects of Cocaine

Cocaine is traditionally thought to exert its effects on behavior by interacting with dopamine transporters. However, recent research, cofunded by NIDA, has shown that other mechanisms may also mediate the behavioral effects of the drug. The research team led by Dr. Rae Matsumoto from the University of Oklahoma Health Sciences Center has demonstrated that interfering with cocaine’s access to sigma receptors can block the behavioral and toxic effects of the drug.

Sigma receptors are unique proteins located in many areas of the body, including the brain and the heart, which are target organs for the actions of cocaine. The research team interfered with cocaine’s access to sigma receptors by treating mice with antagonists or antisense oligodeoxynucleotides. An antagonist is a chemical compound that competes with drugs such as cocaine for occupancy of the receptor. Antisense oligodeoxynucleotides reduce the number of receptors in the body by decreasing the formation of new receptors. When old receptors are degraded, they are not replaced.

The researchers showed that when mice were treated with sigma receptor antagonists and then exposed to cocaine, they were less likely to experience the toxic effects of the drug. The effectiveness of the antagonists in preventing the toxic effects of cocaine appears related to their ability to interact with sigma receptors, rather than dopamine transporters. Additionally, the hyperactivity produced by cocaine was reduced in mice when they received antagonist treatments, showing a reduced sensitivity to the stimulant effects of cocaine.

When the researchers treated mice with antisense oligodeoxynucleotides to reduce the number of sigma receptors in the brain, the animals were much less responsive to cocaine. When exposed to cocaine, antisense-treated mice exhibited behaviors similar to placeboexposed mice, instead of toxic or locomotor stimulant effects.

The result with either strategy (antagonist or antisense oligodeoxynucleotide) is a reduction in sites in the body through which cocaine can produce its actions.

A similar relationship between cocaine and sigma receptors was demonstrated in a separate study in which mice were administered a series of rimcazole analogs that were synthesized in the laboratory of Dr. Amy Newman at the National Institute on Drug Abuse Intramural Research Program. After cocaine exposure, mice were observed for the loss of the ability to right themselves and to control movements. The compounds were shown to attenuate the effects of cocaine through sigma receptors. When the compounds were ranked according to their effectiveness, there was a significant correlation between their protective effects and their affinities for sigma receptors, rather than dopamine transporters.

• WHAT IT MEANS: These findings indicate that sigma receptors may mediate some of the toxic and behavioral effects of cocaine. Sigma receptor antagonists may be possible pharmacotherapeutic agents for treating cocaine abuse.
  
  

These studies were published by Dr. Matsumoto and colleagues in the June 2002 and the November 2001 issues of Neuropharmacology.

Bupropion May Help Schizophrenic Patients Quit Smoking

Smokers diagnosed with schizophrenia had higher smoking cessation rates when treated with bupropion than with a placebo, according to a study led by Dr. Tony George at Yale University. Bupropion is a medication used to help people quit smoking and to treat depression.

Researchers randomly assigned 32 schizophrenic cigarette smokers, who were clinically stable on antipsychotic
medications and with a strong desire to quit smoking, to receive bupropion or placebo for 10 weeks. During the study, participants were periodically evaluated for smoking urges, depression, and symptoms of schizophrenia. They also attended weekly smoking cessation group therapy that included motivational enhancement therapy, social skills training, and relapse-prevention strategies.

At the end of the study, 50 percent of the participants who received bupropion reported that they had quit smoking, compared with about 12 percent who received a placebo. Smoking abstinence was objectively verified with breath carbon monoxide levels. Further, more than 37 percent of those who received bupropion and less than 13 percent of those who received a placebo remained abstinent from smoking during the last four weeks of the study. Bupropion significantly reduced the negative symptoms of schizophrenia—poor motivation, lack of emotional expression, and inability to form appropriate social relationships. It had no effect, however, on cravings for tobacco or depression.

Patients treated with the newer atypical antipsychotic medications, rather than traditional antipsychotic medications, had better smoking cessation outcomes with bupropion.

• WHAT IT MEANS: The findings of this study indicate that bupropion may be a safe and effective treatment for nicotine addiction in schizophrenic patients.
  
  

This study, funded in part by the National Institute on Drug Abuse, is published in the July, 2002 issue of Biological Psychiatry.

Publication News

Issue of Journal of Substance Abuse Treatment Focuses on NIDA Blending Conference

The September 2002 issue of the Journal of Substance Abuse Treatment was comprised of papers emanating from the November 2000 National Institute on Drug Abuse (NIDA) conference entitled “Blending Clinical Practice and Research: Forging Partnerships To Enhance Drug Addiction Treatment.”

The conference, held in Los Angeles, California, was a forum for researchers and practitioners to come together to exchange information, ideas, and perspectives about treating drug addiction. The event attracted more than 850 participants, including drug addiction researchers and drug treatment professionals from the Los Angeles area. Other participants included researchers and community treatment providers from NIDA’s National Drug Abuse Treatment Clinical Trials Network (CTN), a research infrastructure then comprising 14 research centers dedicated to testing the effectiveness of drug treatment interventions with diverse populations in real-life community settings.

Conference presentations helped set the “blending” theme by highlighting the importance of creating synergy between substance abuse research and practice.

The articles contained in the Journal of Substance Abuse Treatment highlight several topics addressed at the conference. They include advances in pharmacological and behavioral therapies for drug addiction, treatment approaches in response to recent trends in drug abuse, updates on existing therapies, and interventions tailored to special populations, such as adolescents, women, and men who have sex with men.

The conference was cosponsored by NIDA, The Robert Wood Johnson Foundation, the University of California at Los Angeles, the Matrix Institute on Addictions, and the Los Angeles County Alcohol and Drug Programs Office.

Funding News

NIDA Grant to the University of Washington Establishes Center to Study Hepatitis-Induced Liver Disease

NIDA has awarded a $9 million grant to the University of Washington (UW) to establish a new Center for Functional Genomics and Hepatitis C Virus-Associated Liver Disease.

The primary goal of the center will be to gain a detailed understanding of the molecular mechanisms underlying the progression from chronic hepatitis C virus (HCV) infection to end-stage liver disease, including cirrhosis and liver cancer. Modern genomics, protein studies and computational technologies will be utilized in this endeavor.
Hepatitis C has emerged as the most important cause of advanced liver disease, cirrhosis and cancer of the liver in the United States. HCV is going to be the major public health crisis of the 21st century-—larger than HIV. The greatest number of new cases is from intravenous drug use.

Dr. Glen Hanson, Acting NIDA Director, says “Among the questions researchers at this new center hope to answer is why some individuals can harbor the hepatitis C virus for years without apparent liver damage while others develop progressive scarring of the liver resulting in cirrhosis and even death.”

The center, directed by Dr. Michael Katze, UW professor of microbiology, includes a diverse group of NIH-funded investigators, including experts from the UW, the Institute for Systems Biology (ISB) and other institutions.

“A distinctive aspect of this center is that we have gathered many of the world’s experts in viral hepatitis, liver disease and transplantation, global gene expression analysis, proteomics, and advanced information technologies in one center to study liver disease,” says Dr. Katze. “The collaboration with the UW transplant team provides access to HCV-infected liver samples that will allow us to study the disease in patient tissues. Historically, HCV has been difficult to culture in a laboratory setting, so patient samples will provide a wealth of information that cannot be obtained any other way.”

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 further information on NIDA research can be found on the NIDA web site at http://www.drugabuse.gov.