Congressional Justification
Authorizing Legislation: Section 301 of the Public Health Service Act, as amended. Reauthorizing legislation will be submitted.
| Budget Authority: | |||||
| FY 2001 Actual | FY 2002 Appropriation | FY 2002 Current Estimate | FY 2003 Estimate | Increase or Decrease | |
| Current Law BA | $789,010,000 | $888,105,000 | $887,733,000 | $964,613,000 | $76,880,000 |
| Accrued Costs | $2,962,000 | $3,205,000 | $3,205,000 | $3,285,000 | $80,000 |
| Proposed Law BA | $791,972,000 | $891,310,000 | $890,938,000 | $967,898,000 | $76,960,000 |
| FTE | 370 | 384 | 384 | 382 | -2 |
This document provides justification for the Fiscal Year 2003 activities of the National Institute on Drug Abuse (NIDA), including HIV/AIDS activities. A more detailed description of NIH-wide Fiscal Year 2003 HIV/AIDS activities can be found in the NIH section entitled "Office of AIDS Research (OAR)".
The President’s appropriations request of $967,898,000 for this account includes current law adjusted by assuming Congressional action on the proposed Managerial Flexibility Act of 2001.
Introduction
Americans continue to see illegal drugs as one of the top problems in the country and view it as one of the most important problems facing teenagers today (Harvard School of Public Health/Robert Wood Johnson Foundation, 2000). Fortunately, our Nation has a strong research foundation to help alleviate this complex public health problem. The National Institute on Drug Abuse (NIDA) supports a broad comprehensive research and research training portfolio that addresses all drugs of abuse, both legal and illegal. The ultimate aim of our Nation’s investment in drug abuse research is to enable society to prevent drug abuse and addiction, and to reduce the adverse individual, social, health, and economic consequences associated with drugs. Also, given that drug abuse is a major vector for the spread of HIV/AIDS and other blood-borne diseases, such as hepatitis, reducing the medical consequences associated with drug abuse remains a high priority for the Institute.
We have made much progress in this regard. Over the past several years, for example, powerful research tools and extraordinary science advances have allowed a core concept to evolve that continues to change our Nation’s approach to drug abuse and addiction. This core concept is the recognition of drug addiction as a brain disease that develops over time as result of the initially voluntary behavior of using a drug. This is now an accepted concept by most healthcare professionals, policy makers, and the majority of the American public. This biomedical model has significant implications for how we approach the prevention and treatment of drug abuse and addiction.
We now know more about how drugs act in the brain and body than at any time in history. We know that there are commonalities to all addictions. Whether someone becomes addicted to amphetamines, cocaine, nicotine, alcohol, or even food in the case of compulsive overeaters, the brain mechanisms that are affected appear to be similar. For example, numerous studies, including those where neuroimaging techniques are utilized, show that there is a spike or increase in the functional activity of the neurotransmitter dopamine. Dopamine is an important brain chemical that allows us to feel the sensation of pleasure. There are also persistent changes in cellular processes in the brain that appear common to all addictive substances.
Research in both animals and in humans has taught us that drugs can cause long-lasting injury to the human brain. Methamphetamine, for example, has been shown to be particularly damaging to the dopamine system. The reduction in dopamine transporters (DAT) that we can see with this drug is believed to be a result of neuronal toxicity. This loss, in turn, affects an individual’s emotional and cognitive functioning. But, there is now a body of research emerging that suggests that prolonged abstinence from drugs allows at least some aspects of brain function to recover from this damage. Chronic methamphetamine users who remained drug free for almost two years were able to regain DAT losses, however it is still unclear if the former users regain full cognitive function. These findings are providing us with renewed hope and new research opportunities.
We are also learning more about how an individual transitions from an occasional drug user to one who compulsively seeks and use drugs, despite the known detrimental consequences. Although over 2 million Americans used an illicit drug for the first time in 1999, (Summary of Findings from the 2000 National Household Survey on Drug Abuse, DHHS, SAMHSA, September 2001) only a very small percent of them will go on to become drug addicts. Why is this? What makes some individuals more vulnerable to addiction than others? Science is providing us with more insight into this perplexing question as well. Since the launch of our “transition to addiction” initiative last year, we have found that there are neuroadaptations occurring at all levels, including the cellular, molecular, and even at the synapse level. As we continue to learn about which genes and proteins are being turned on and off during drug exposure and how this relates to the transition to addiction, we are also finding out more about the important role that memory plays in the addiction phenomenon.
Memory has long been thought to play a role in causing relapse to addiction. For example, the mere mention or viewing of drug paraphernalia or places frequently visited by former drug addicts is enough to cause addicted individuals to report intense craving for drugs that have long been eliminated from their bodies. A new study has revealed some powerful data about the pivotal role that memory actually plays in drug abuse. Craving for drugs has been found to be associated with the same brain circuits involved in response to other non-drug stimuli. Through self-reports and functional magnetic resonance imaging, researchers found that regions of the brain that were activated during cocaine craving were the same regions activated by individuals watching sexually explicit videos suggesting that a person’s craving for drugs can override all other motivational priorities. The memory of drugs appears to be even more powerful than we originally thought.
All of these neuroscience advances are leading us to improved ways to treat addiction. The biological nature of this disease explains why addicts cannot just quit on their own and why treatment is so essential. The complexity of this disease also makes it clear that not just anything called treatment will do. These are just some of the reasons why NIDA established a science-based treatment infrastructure in this country, known as the National Drug Abuse Treatment Clinical Trials Network (CTN).
The CTN was designed to be the vehicle to improve the quality of drug addiction treatment nationwide, similar to the successful models employed by other NIH institutes for bringing new treatments for cancer and heart disease to the citizens of this Nation. The CTN allows us to bring the benefits of increasingly sophisticated scientific discovery to the American people more rapidly than ever before. It is designed to test promising innovative behavioral treatments and medications in real-life treatment settings. Since its inception barely two years ago, more than a dozen research protocols have been developed and are being systematically tested in communities throughout the Nation. From a research perspective, not only do we see the CTN benefitting the thousands of patients that are currently enrolled in its clinical trials, but we also see the momentous benefits to the researchers and practitioners involved in this endeavor as well. By having researchers and practitioners work side by side to develop and apply research findings in treatment settings, we are literally “blending” research and practice and making treatments even better for the patient. This “blending” initiative will continue to be a high priority for NIDA.
Research from throughout our portfolio is yielding important treatment advances. For example, the first large-scale study to evaluate treatment outcomes for adolescents found that community-based treatment programs that are specifically tailored to adolescents populations can be effective in reducing drug use, criminal activity, and improving school performance. Our behavioral treatment portfolio continues to provide us with further proof that therapies such as contingency management, where patients are provided with incentives to remain drug free, do in fact work. These efficacious therapies are being adapted to workplace and other community settings and are showing sustainable results that demonstrate the long-term outcomes achieved by behavioral therapies. Our medications development program also continues to bring new compounds and pharmacotherapies to the treatment pipeline. Promising medications for cocaine addiction, such as disulfiram and selegeline, will likely begin Phase III clinical trials this year.
Just as we are using science to improve the quality of addiction treatment nationwide, we plan to do the same in the prevention arena. Building on the successful implementation of our CTN and our Tobacco Transdisciplinary Use Research Centers, which we support with the National Cancer Institute and the Robert Wood Johnson Foundation, NIDA is about to change how we approach drug prevention in this country. As our Nation looks for the most effective and cost effective ways to prevent drug use, NIDA will bring the full power of science to bear on this challenging problem through the National Drug Abuse Prevention Research Initiative. Announced at our Prevention Conference in Fall 2001, the initiative will include a number of new activities, including the creation of Transdisciplinary Prevention Research Centers that will bring researchers and practitioners together to tackle unanswered research questions, such as how the adolescent decision-making process occurs and how we can use the media and other communication strategies to reach adolescents. As part of this initiative, NIDA will also rely on basic neurobiology to develop new directions for effective prevention efforts. For example, discoveries from the field of neuroscience may be used to facilitate the identification of biological mediators as targets for intervention. Additionally, NIDA plans to launch multi-site prevention trials that will test the effectiveness of drug abuse prevention programs in diverse populations across the country and encourage the local adoption of programs that are vigorously evaluated.
Additionally, NIDA will continue to keep its finger on the pulse of drug use in America and be ready to detect and use science to curtail any emerging drug or drug-related health consequences that may threaten the safety of our citizens. We take pride in our ability to rapidly disseminate our findings so that communities can mobilize a public health response. In the past year we have increased awareness and provided scientific knowledge about 3,4-methylenedioxymeth-amphetamine (MDMA), inhalants, steroids and the abuse of prescription drugs through a number of venues. By bringing together the world’s leading researchers in the Summer of 2001 for a scientific meeting on MDMA, for example, we were able to provide scientific evidence that demonstrates without a doubt that MDMA is anything but a benign drug. The meeting also provided a public venue to identify new research opportunities and to educate people about the science and the dangers of MDMA. We are also making an extra effort to provide teachers with science-based user friendly slide and CD-ROM teaching packets to use in classrooms as they educate their students about drugs of abuse, such as MDMA.
All in all, we have had a tremendous year of progress in understanding, preventing, and treating drug abuse and addiction.
New Initiatives
Reducing the Burden of Addiction by Bringing New and Improved Treatments to Clinical Trials.
Determining new ways to treat addiction will continue to be a high priority for NIDA. We will continue to develop a strong infrastructure for supporting clinical studies to ensure a mechanism is in place to investigate real-world effectiveness of drug addiction research. Clinical trials are the gold standard for testing whether a therapy or preventive measure really works, or works better than the best proven results. Toward this end, several addiction medications will likely enter Phase III trials this year, increasing the number of people who could potentially benefit from new medications. NIDA will begin Phase III studies this year on two medications (selegeline and disulfiram) that are showing great promise in treating cocaine addiction. Disulfiram, also known as Antabuse, is currently approved for treatment of alcoholism and has shown efficacy in reducing cocaine use in at least five outpatient studies. Selegeline, which has been approved as a treatment for Parkinson’s Disease, is also showing success in cocaine-addicted populations. Both of these drugs will also be explored as potential treatments for methamphetamine addiction.
A New Era of Prevention Research.
NIDA is ushering in a new era of prevention research that will bring together a broader array of scientific disciplines to reduce drug use in this country. By bringing together basic, clinical, and applied researchers who can tackle questions such as how do cognition and emotion affect adolescent decision-making, NIDA will be in a better position to develop and implement more effective preventive strategies at the individual, family and community levels. By expanding upon its National Prevention Research Initiative (NPRI), NIDA is continuing to set the stage for the establishment of new science-based approaches to prevention. The NPRI will include several complementary components. First, the Multi-Site Trials component will involve a number of partners that work together to test the effectiveness of new and existing science-based prevention approaches in different communities, while simultaneously studying how best to adapt the programs for local communities. Second, the Transdisciplinary Prevention Research Centers will foster collaborations between neuroscientists, behavioral scientists, cognitive scientists and drug abuse prevention researchers, with input from practitioners in the prevention community to address knowledge gap areas, such as the role that prevention messages and communications strategies can play in influencing adolescent behaviors relating to drug abuse, as well as how to approach the scientific questions in drug abuse prevention research in new ways. Thirdly, NIDA will encourage basic neuroscience and behavioral researchers to address fundamental questions that can lead to new and/or improved prevention strategies. By integrating the work of basic, clinical, and applied scientists, NIDA will gain a greater understanding of how best to use science to reduce the burden of drug abuse and addiction in this country.
Expanding the National Drug Abuse Treatment Clinical Trials Network (CTN).
This infrastructure, established in 1999, is now enabling us to move treatment research into practice. NIDA will continue to increase the number of research protocols and patients participating in the geographically dispersed research centers that comprise the CTN. In FY 03, NIDA plans to expand the reach of the CTN to new populations and regions underrepresented in the health care system, including individuals who have co-morbid mental illnesses, those suffering from HIV/AIDS or other infectious diseases, and court-diverted populations. NIDA also plans to establish CTN nodes into regions of the country that may not have easy access to quality treatment and/or are not currently part of the CTN structure. NIDA is especially interested in involving the private sector in CTN activities at a variety of levels, from helping disseminate the research findings, to getting private practitioners more involved and invested in drug addiction treatment. There are also plans to begin clinical trials in other countries who have expressed a desire to participate and have patient populations that may meet the protocol requirements.
Exploring the Link Between Stress and Drug Abuse.
As our Nation continues to recover from the terrorist attacks that occurred in September 2001 and to cope with the fear of ongoing threats against our country, NIDA will expand its research portfolio to further examine the role that stress plays in the initiation and reinstatement of drug use. At the basic research level, NIDA will examine the role that both acute and chronic stress play in changing circuitry in the brain that in turn affects behavior. Other areas of NIDA’s research portfolio will also focus on this issue of stress. For example, epidemiologists, ethnographers, and prevention researchers will be looking more closely at drug use prevalence rates following the September attacks. Researchers with expertise in treating individuals who have drug abuse problems will team with health service delivery experts to determine which science-based interventions would be most useful to populations that appear to be more vulnerable to drug use. NIDA’s medications development program will pursue the development of corticotropin releasing factor antagonists as potential addiction medications. Finally, NIDA will continue to educate the public and health care providers about this topic.
Using Advances in Genetics to Identify “the Switch.”
An array of new technologies, such as microarrays, which can simultaneously analyze the activity of thousands of genes, are allowing researchers to better elucidate the molecular and cellular mechanisms by which voluntary drug use can evolve over time into addiction. The utilization of microarrays will make it possible to find the genes that are involved in addiction, help determine their role in cellular processing, and determine how they may be involved in an individual’s transition from a drug user to a drug addict. In addition, the growing field of proteomics will help us determine how these genes are working to mediate this transition. NIDA will participate in NIH’s newly formed Proteomics Interest Group to ensure that state-of the-art knowledge is used to advance the field.
Reducing the Burden of Tobacco-Related Diseases By Fighting the Addiction.
Because addiction to the drug nicotine drives the continued use of tobacco in this country and abroad, NIDA’s comprehensive research portfolio will help enhance National efforts to reverse the tide of tobacco-related diseases, including cancer. Recognizing that smoking cessation remains among the most cost-effective approaches to reducing cancer risk, in the upcoming fiscal year, NIDA will work with the National Cancer Institute to accelerate the identification of new treatments for nicotine addiction. A NCI/NIDA Working Group on Pharmacologic Approaches to Nicotine Addiction has recently been established and progress is being made in identifying promising new compounds that can be developed and tested in clinical trial settings. In addition to enhancing NIDA’s nicotine treatment portfolio, NIDA will utilize research findings from its entire portfolio to prevent and treat addiction to nicotine. For example, NIDA will utilize new findings from its genetic research portfolio to better tailor treatments to an individual’s genetic makeup. NIDA will work to develop treatment interventions for adolescents. NIDA will also continue to collaborate with NCI and the Robert Wood Johnson Foundation to support the research that is underway at the 7 Transdisciplinary Tobacco Use Research Centers across the country.
Employing New Mechanisms to Support Innovative Research.
NIDA is employing a number of new mechanisms to foster innovative research and research opportunities for new investigators that will more rapidly advance our understanding of drug abuse and addiction. For example, NIDA’s “Cutting Edge Basic Research Awards (CEBRA)” is allowing NIDA to fund research that is high risk and potentially high-impact and that is underrepresented or not included in NIDA’s current portfolio. Another new award mechanism will be created that more rapidly funds new investigators who want to work in the neuroimaging arena. This new mechanism, known as “I-START: Rapid Funding for New Investigators in Brain Imaging” will stimulate growth in the cutting edge field of neuroimaging, I-START, like its model predecessor the Behavioral Science Track Award for Rapid Transition program, can expedite the entry of newly independent investigators into the drug addiction research field by offering small one-year grants to jump start their research careers.
Improving Care for Chronic Drug Users to Reduce the Spread of HIV and other Blood-borne Diseases.
A complex relationship exists between drug abuse and addiction and the transmission and progression of HIV/AIDS and other blood-borne diseases. NIDA will increase its research focus on the epidemiology and prevention of HIV and other blood-borne infections in drug-using populations. Since engagement and retention of drug users in drug abuse treatment are part of effective HIV/AIDS prevention strategies, NIDA will also encourage research in these areas. New research that shows adolescents are willing to enter treatment and learn about their HIV serostatus will encourage treatment providers to develop new approaches or adapt existing approaches that more effectively meet the needs of adolescent populations. The special needs and concerns of HIV-infected clients and the importance of HIV prevention have led to new initiatives in drug abuse treatment and the modification of existing drug abuse treatment practices. Given that injection drug users (IDUs) have a pivotal role in the epidemics of blood-borne diseases, such as hepatitis and HIV/AIDS, NIDA will continue to work with communities and other leading public health agencies to implement a comprehensive prevention and treatment approach toward this population. This approach takes the life circumstances of IDUs, as well as their cultures and languages, behaviors, and readiness to change into account.
Finally, NIDA will support research on the relationships between larger contextual factors and risks of disease, particularly among drug-using populations, such as socioeconomic status, social capital, characteristics of the community, violence, environmental factors, and healthcare and other institutions. Research findings will inform the development of new approaches to prevent drug abuse and the spread of new infections, particularly in adolescent populations. NIDA will also support research on drug-drug interactions among various antiretroviral medications and those used in the treatment of drug addiction.
Addressing Health Disparities.
NIDA research shows that, contrary to a common stereotype, overall rates of drug abuse among racial and ethnic minorities are similar to rates in the general population, although some aspects of drug abuse may differ. We also know that some populations suffer disproportionately from the consequences of drug abuse. NIDA will continue to make a concerted effort to better understand and address the drug abuse and addiction research needs of racial/ethnic minority populations, focusing on areas where there are significant gaps in knowledge and clear disparities in prevention, treatment, and health services in these communities. NIDA will implement the strategies outlined in its “Strategic Plan on Reducing Health Disparities” and will work toward implementing research gap areas identified at its national conference in September 2001, “Bridging Science and Culture to Improve Drug Abuse Research in Minority Communities.” NIDA’s Health Disparities Initiative will focus on four major research areas: epidemiology, prevention, treatment, and basic and clinical research. In some cases, these efforts will represent an expanded commitment to existing programs, but the initiative also will include important new activities. For example, NIDA will expand training opportunities to increase the capacity of minority institutions – and the number of minority scientists – involved in drug abuse research. NIDA will also encourage more research on studies that foster cross-disciplinary biomedical, epidemiological, developmental, and social science research to develop more effective interventions to reduce the impact of HIV/AIDS and other disease consequences of drug abuse in minority populations.
Story of Discovery - From Concept to Clinical Trials: Improving the Quality of Drug Addiction Treatment Through Research
“Sometimes it takes years for research results to affect treatment delivery,” (IOM, 1998). To shorten this lag time and to bridge the gap between scientific discovery and clinical practice, the National Institute on Drug Abuse (NIDA) has established a new infrastructure that brings drug abuse researchers and real world treatment providers together to dramatically improve the quality of drug addiction treatment in this country.
In recent years, NIDA research has produced an array of pharmacological and behavioral interventions that show great promise for improving drug abuse treatment. Treatments such as cognitive behavioral therapies; motivational enhancement strategies; contingency management; and medications such as buprenorphine for detoxification have been shown to reduce drug abuse among patients in research settings. Until very recently there was no true outlet for these evidence-based treatments to flourish. With the establishment of the National Drug Abuse Treatment Clinical Trials Network (CTN) in the fall of 1999, this was about to change.
Behavioral, pharmacological, and integrated behavioral and pharmacological treatment interventions that were shown to be effective in restricted patient populations could now undergo rigorous review in multisite clinical trials. Diversified patient populations across the country could now have access to quality treatments. And importantly, researchers and practitioner would be accomplishing this together. By having researchers and practitioners working together to ask and answer the right questions relevant to clinical practice and by having them jointly commit to the successful implementation of new treatments is a good idea that is quickly becoming a reality in the field of drug abuse.
The idea of developing meaningful collaborations that contribute to effective responses to social and clinical problems has been around since Kurt Lewin developed the concept of “action research” in the late 1940s. Although Lewin and his colleagues were not specifically studying treatment programs for alcohol and drug addiction, their findings, which demonstrated the feasibility of conducting research in real life settings remains applicable today. The National Cancer Institute’s Community Clinical Oncology Program, which has effectively linked cancer research and treatment for almost two decades (since 1983), shows how a collaborative model can be adapted to the biomedical arena. By involving community oncologists and community-based primary care physicians in NCI-approved clinical trials, state-of-the-art cancer treatment and prevention is being brought to local communities. The gap between policy, research, and treatment is being bridged in the cancer arena. NIDA wanted to do the same for people who suffer from drug addiction.
It was with the cancer model in mind, that the principle recommendation from the 1998 Institute of Medicine Report “Bridging the Gap Between Research and Practice” emerged calling for NIDA to support the development of an infrastructure to facilitate research within a network of community-based treatment programs. This recommendation also coincided with the science. NIDA’s science, especially in the treatment arena, had matured to a point where it was ready to be taken to the next level, in this case to multi-site clinical trials. Both the timing and the science was right. An array of treatments that were shown to be effective under carefully controlled conditions were now ready to be adapted and applied effectively with diverse patient populations in a variety of treatment settings.
With a large pipeline of behavioral and pharmacological science-based treatments, a budget that could support an effort of this magnitude, and a willing group of staff, researchers and community treatment program providers and practitioners, in tow, NIDA began to change how we approach addiction in this country. NIDA based the design of the CTN infrastructure on other successful clinical trials models used at NIH. The CTN was to become a national network comprised of geographically diverse, Regional Research Nodes working collaboratively with NIDA staff and community-based treatment providers. Through collaborations between the researchers and treatment providers, science-based treatments would be tested and adapted for suitable implementation in real life settings. This is in fact what is happening.
Since awarding the first five grants in September 1999, the CTN has grown to include 14 CTN centers that are spread across the country. Each CTN center consists of a “node” typically located at an academic center that is partnering with up to 10 community treatment programs in the region. We now have more than 90 community-based treatment providers participating in this research venture that currently enrolled more than 3,600 patients in the trials.
The full involvement of both scientists and practitioners in all aspects of the CTN’s work, especially the development of protocols, is the hallmark of the CTN. The six treatment protocols currently accruing patients in the CTN and the six that are about to begin enrolling patients, were all developed jointly by both researchers and community-treatment providers. This collaborative venture ensures that all protocols run in the CTN retain the science base of new treatments, while also ensuring that they are applicable in the clinic. This, in turn will directly benefit the patients seeking addiction treatment. It also brings us one step closer to putting addiction treatments on a more equal par with other diseases. The more than 4 million people in need of drug addiction treatment (National Drug Control Strategy: 2001 Annual Report, Office of National Drug Control Policy) in this country deserve quality treatments and the CTN is making that a reality.
NIDA Science Advances
Drugs, Food, and Gambling: Is there a Commonality?
In recent years, research has demonstrated that all drugs of abuse, be it cocaine, heroin, methamphetamine or nicotine, are able to increase levels of the neurotransmitter dopamine in the brain circuits that have been shown to mediate reward and reinforcement. Now, two studies are showing that some of these same mechanisms also appear to be involved in gambling and obesity. In a study of men participating in a monetary game of chance, functional magnetic resonance imaging (fMRI) was used to map brain activity during the game. The pattern of brain activity observed during the “expectancy” and “outcome” phases of the game is strikingly similar to the responses to cocaine administered to cocaine addicts in previous studies suggesting that these brain circuits mediate the response to diverse and highly rewarding stimuli. Another study of pathologically obese (body mass index (BMI) greater than 50) individuals, found that pathological over-eating seems to be associated with reduced dopamine function. The two studies suggest that the brain circuits that may account for some of these behaviors are the same ones reported to be involved in drug addiction. These potential commonalities among addictions, whether it be food, gambling, or drugs, support the idea that dysfunction of brain processes crucial to decision-making and behavior may contribute to a broad range of problems
New Evidence Suggests that the Brain May Have the Capacity to Recover From Long-term Exposure to Methamphetamine After Prolonged Abstinence.
The stimulant methamphetamine continues to be abused throughout the world. Not only is methamphetamine highly addictive, but it has been shown in both animals and in humans to impair dopamine neurons as indicated by decreases in the number of dopamine transporters (DAT) in the brain. Neural changes have been found to persist several weeks, months, and years following the last drug exposure. A new neuroimaging study provides the first evidence in humans that the dopamine transporter losses which are thought to reflect actual loss of dopamine containing neurons known to occur from chronic methamphetamine exposure can recover significantly with long term abstinence. However neuropsychological function did not recover with protracted abstinence, suggesting that although there is recovery of DAT levels there is not a parallel improvement in function. This finding has tremendous implications not only for drug addiction researchers, but those studying other neurodegenerative disorders such as Parkinson’s and Alzheimer’s.
Effects of Cocaine on the Developing Brain.
In a series of non-human studies, a team of researchers found that prenatal cocaine exposure interferes with nerve cell production and leads to a significant increase in cell death in the developing cerebral cortex. The team developed a non-human primate model by investigating the dosage and route of cocaine administration for studies in pregnant monkeys that is most relevant to humans. Using this model, the researchers looked at cocaine’s effect on nerve cells in the offspring’s cerebral cortex. They gave pregnant monkeys cocaine during their second trimester and allowed them to deliver on time. When the offspring were three years old, the researchers examined each brain and found that the cerebral cortex lacked its normal, multi-layered, highly organized structure and contained nearly 50 percent fewer neuronal cells than the cortex of a non-drug-treated monkey. They also found a significant increase in the number of cells below the cortex in the white matter of the brains. Finally, they examined the cerebral cortex in monkeys exposed to cocaine during the first, second, or third trimester of pregnancy, and found that the cortex was affected only in monkeys exposed to cocaine during the second trimester. Although these studies can not directly be applied to humans, the results provide important insight on the effects of prenatal cocaine exposure on the developing brain.
HIV Testing of Youth in Substance Abuse Treatment Can Potentially Reduce the Burden of the Disease.
Researchers found that HIV testing is feasible and acceptable for hard to reach young adults and adolescents in substance abuse treatment and is especially effective if the results can be presented while the individual is still in treatment. Researchers offered HIV testing to 204 inpatients, ages 18 to 25. The researchers discovered that of 204 participants offered HIV testing, 74 percent accepted. All inpatients accepting testing chose the oral test (vs. a serum-based test). Almost 65 percent of patients received their results while still in the facility. Less than 10 percent of those requiring a return-appointment to receive their results followed through with results-disclosure, suggesting that rapid HIV testing with same day results could significantly increase the proportion of youth at highest risk for HIV who learn their serostatus.
MDMA Use During Pregnancy Can Impair Memory and Learning In Offspring.
Researchers have found the first evidence that prenatal use of MDMA or “Ecstacy,” may cause memory loss and other impairments in offspring. Newborn rats were given MDMA on days 1-10 or 11-20 (time frames similar to brain and central nervous system development in humans during the early and late third trimester). The subjects ability to perform in learning and memory tasks were observed. The subjects had no difficulty learning a cued version of a swimming maze. However, when the subjects were faced with spatial learning and probe or memory trials, memory and learning deficiencies were detected in the subjects exposed to MDMA on days 11-20. The findings suggest that MDMA has selective effects on cognitive development during the CNS development cycle. The learning deficits were found to be long-term, meaning they were seen in the offsrping as adults.
Despite Lower Initial HIV Blood Levels in Women, Men and Women Develop AIDS at Similar Rates.
Researchers discovered that although during the first years of HIV infection women have significantly lower amounts of HIV in their blood than men, both men and women had a similar risk of developing AIDS. The team found that the median initial viral load of the 15 women who progressed to AIDS was about 4.5 times lower than that of the 29 men who progressed to AIDS. Yet, the men and women experienced a similarly swift rate of loss of their CD4+ T cells, the immune cells that decrease as a result of HIV infection. Previous studies in men show that initial viral load can be used to gauge their likelihood of progression to AIDS, but these data confirm that the initial viral load is much lower in women than in men and consequently not as predictive for women. The investigators found that the women who developed AIDS had an average initial viral load of 17,149 copies of virus per milliliter (ml) of blood versus men who progressed to AIDS whose average was 77,822 copies/ml. Even men in the group who never developed AIDS had a higher median initial viral load of 40,634 copies/ml of blood.
Even a Single Exposure to Cocaine Can Alter Brain Function.
Scientists have recently identified changes in the brain that occur with only a single exposure to cocaine. In this study, researchers studied the brains of rodents who were given either one dose of cocaine or saline as a control. They found that neural connections in a part of the brain known at the ventral tegmental area (VTA) were altered by just a single dose of cocaine. The VTA is involved in the rewarding aspects of cocaine, as well as certain aspects of learning and memory. This study also demonstrated that the changes that occurred in the VTA were still present five days after the single dose of cocaine, indicating that even a single exposure to cocaine can cause long-term changes in the brain. These findings indicate that just one use of a drug such as cocaine may be enough to cause brain changes that, in some individuals, could trigger compulsive use – perhaps flipping the proverbial “switch” for addiction.
Public Service Announcements Geared to Address Teens’ Specific Motivation to Use Drugs Can Reduce Drug Use.
Researchers recently reported that they could reduce marijuana use among a targeted group of teens by focusing on their specific underlying emotional styles. By developing anti-marijuana PSAs that appeal to high sensation seeking adolescents and placing them in programs likely watched by these teens, the researchers found that marijuana use among this group was reduced by about 26 percent. Sensation seeking is a personality trait associated with the willingness to take risks to obtain intense stimulation and has been shown to be correlated with the use of a variety of drugs and use at an earlier age. An average of 777 paid spots and 1,160 unpaid spots were aired in 3 similar communities in Kentucky and Tennessee. At least 70 percent of the targeted age group was exposed to a minimum of three PSAs a week. The campaigns were successful in reversing the usual trend of more teens beginning to use marijuana as they get older. In one community, effects of the campaign still were evident several months after its conclusion. There, the estimated drop in the relative proportion of high sensation seekers using marijuana was 26.7 percent. The campaigns had no effect on teens characterized as low sensation seekers, a group that already exhibited low levels of marijuana use.
Marijuana Use in Early Adolescence Can Lead to Psychiatric Problems as an Adult.
There’s an age old question in the addiction and mental health arena: Which comes first - - the drug use or the psychiatric disorder? In both clinical and general population samples of adolescents and adults, psychiatric disorders have been found to be related to psychiatric disorders. A recent study investigating the link between marijuana use, depressive symptoms, anxiety, and interpersonal aggression was conducted using two sets of interviews two years apart with over 2,200 Colombian teens between the ages of 12 and 17. Trained interviewers talked to adolescents in their homes in three Colombian cities, obtaining information about frequency of marijuana use and symptoms of anxiety and depression. They then performed two sets of analysis. Unlike other studies, this study did not find that anxiety and depression led to increased marijuana use. Instead, the researchers found that marijuana use in early adolescence is associated with higher levels of anxiety, depressive symptoms, and interpersonal aggression in late adolescence all of which may persist into adulthood. Leading to the conclusion that development of drug use preceded psychiatric symptoms in the studied population, suggesting that at certain stages of adolescent development, drug use should be considered a risk factor for the later development of psychiatric disorders and problem behaviors, as well as the inability to assume adult roles in society.
Reducing Women’s Concern About Weight Gain Improves Smoking Cessation Rates.
Stopping smoking is rarely easy. Research shows that it is often more difficult for women to quit than it is for men. One of the reasons for this is that women may be more concerned about the weight gain that often accompanies a quit attempt than men. Researchers found that treatment for addiction to nicotine that focused on reducing concerns about weight gain can significantly improve smoking cessation in women. Investigators randomly assigned 219 women smokers who wanted to stop smoking, but were worried about gaining weight, to one of three smoking cessation groups. One group received standard smoking cessation therapy, where weight gain was not explicitly addressed. Another received the same smoking cessation program plus diet advice. The third group received the standard program plus cognitive behavioral therapy to reduce concern about gaining weight, but dieting was discouraged. One year after treatment, 21 percent of the women who received the third therapy, which was the smoking cessation program plus cognitive therapy to reduce concerns about weight gain, had completely quit smoking (with no relapses), compared to 13 percent of the group that was dieting, and 9 percent of the standard therapy group. Surprisingly, the women in the group receiving cognitive therapy to alleviate weight gain concerns fared best in terms of preventing weight gain. One year after treatment they gained less than the other two groups. On average, they gained about 5.5 pounds, whereas women in the dieting group and the standard therapy groups gained 11.9 pounds and 16.9 pounds, respectively.
Addiction Treatment Programs Specifically Tailored to Adolescents Can Be Effective in Reducing Drug Use, Criminal Activity, and Improving School Performance.
To determine if adolescent treatment programs offered in four major cities were showing positive outcomes after treatment was completed (reduced drug use, reduced criminal activity, improved school performance), NIDA-supported researchers designed the Drug Abuse Treatment Outcome Studies for Adolescents (DATOS-A). This two-year study of 1167 adolescents who ranged in age from 11 to 18 showed that when comparisons were made between the year prior to enrollment to treatment to a year following treatment, significant improvements were made in drug and alcohol use, school performance, and criminal activity. Weekly or frequent marijuana use dropped from about 80 percent to just over 43 percent. Heavy drinking dropped from nearly 34 percent to 20 percent, and criminal activities dropped from just over 75 percent to about 53 percent. Attendance and performance in school also improved following treatment. The researchers also concluded that similar to adult populations, the longer an individual stays in treatment the better the outcomes.
Initiation of Smoking: Genes Plan An Important Role.
The development of tobacco addiction involves many phases including initiation of smoking and the development of nicotine dependence. Research suggests that genetic factors may play a key role in smoking initiation and the progression to nicotine addiction. One candidate gene is the tryptophan hydroxylase (TPH) gene. The TPH gene is critical to the biosynthesis of serotonin, a neurotransmitter whose function is often altered in addiction. Thus, researchers investigated two TPH gene markers in a large population-based study to determine if there is an association between the gene and initiation of smoking or progression to nicotine dependence. The study looked at three groups, those who had never smoked, those who were regular smokers but had low scores on a test for dependence, and regular smokers with high dependence scores. In comparing lifetime nonsmokers with regular smokers, scientists found significantly different allele, genotype, and haplotype frequencies in the TPH gene markers suggesting an association between smoking initiation and the gene. But no significant differences in the TPH gene markers were seen when comparing the two groups of regular smokers. Thus, the gene may not be associated with progression to nicotine addiction.
Potential New Target for the Treatment of HIV.
Successful retroviral infection requires the integration of the viral genome into the host cell DNA. Using genetic knockout technology to delete the enzyme poly(ADP-ribose) polymerase-1 (PARP-1) scientists have discovered that HIV-1 infection can be prevented in mice lacking this nuclear enzyme. Because PARP-1 appears to mediate the integration of the viral genome into the host genome, medications that inhibit this enzyme may be effective in the treatment of HIV.
Morphine Can Alter Immune System Function: The Role of Substance P.
Substance P (SP) is a neuropeptide that communicates between the central nervous system and the immune system, the body’s line of defense against disease, modulating immune and inflammatory responses. Opiates, such as morphine, also modulate the function of the immune system, and now research shows that there is an important connection between morphine and SP. Researchers investigating the effects of morphine on the production of SP and its receptor found that morphine increases the production of SP and its receptor in key human immune cells – mononuclear phagocytes and lymphocytes. Since SP regulates inflammation of the central nervous system and other immunologic events, these results suggest that morphine-induced SP expression in immune system cells may be of importance in the development of immune system related diseases, such as AIDS.
Hepatitis C Risk Is Not Limited to Those Who Inject.
Hepatitis C virus (HCV) infection is a major health problem in the United States. According to the Centers for Disease Control and Prevention and other sources, an estimated 4 million Americans – about 2 percent of the population – are infected and an average of 30,000 new infections occur annually (McQuillan et al.,1997; CDC 1998; Alter et.al,1999). Sixty percent of all new cases of acute HCV infection are attributed to syringe and needle-sharing, thus prevalence of HCV is particularly high among injecting drug users. But researchers conducting a study of the prevalence of HCV infection among New York City drug users found a higher than expected HCV infection rate among non-injecting drug users. Of 107 women and 251 men from the Lower East Side of Manhattan who reported never injecting, 14 percent of the women and 18 percent of the men were found to be infected with HCV. Of 171 women in East Harlem who reported no history of injection drug use, 17 percent were found to be infected. Although these rates were lower than for those with a history of injection drug use (from 54 to 61 percent), they were higher than the general population. The findings may indicate that use of needles and syringes is not the only drug-related risk factor for HCV infection. Thus, research into other routes of HCV transmission among non-injecting drug-users is needed.
New Compound Blocks Marijuana’s High.
Neurobiological studies have discovered that _-9-tetrahydrocannabinol (THC), the primary psychoactive ingredient in marijuana, acts at two receptor subtypes to produce its many effects. THC produces its behavioral, cardiovascular, analgesic, psychomotor, and cognitive effects through interactions primarily with the CB1 cannabinoid receptor. SR141716 is a new compound that blocks the ability of THC to recognize the CB1 receptor. It was tested for its ability to block marijuana’s behavioral and cardiovascular effects in healthy men with a history of marijuana use. In a randomized, placebo controlled, double-blind study, increasing doses of SR141716 were found to attenuate the acute psychological and physiological effects of smoked marijuana. The 90 mg dose of SR141716 (the highest dose tested) produced an almost 50 percent reduction compared to placebo controls in the high produced by a smoked marijuana cigarette. An almost 60 percent reduction in heart rate was also found. SR141716 also appears to be a safe medication in that it produced no significant physiological or behavioral effects and was well tolerated by the subjects.
Researchers Develop Antibodies that Recognize Hepatitis C Virus.
One of the critical problems in controlling hepatitis C virus (HCV) infection is the variability of the virus with more than nine distinct types of virus known. A further complication is the added variability of HCV envelope proteins, E1 and E2. These proteins, especially E2, enable the virus to bind to human immune cells leading to the spread of the disease within the body. In an effort to characterize the HCV envelope proteins and look for ways to prevent binding of the virus to immune cells, particularly T cells, researchers developed several HCV-specific, monoclonal antibodies from a person infected with HCV. The researchers found that not only did several of the antibodies recognize a variety of E2 formations, but several also prevented the binding of E2 to T cells that display a receptor called CD81. The demonstration of broadly effective antibodies in an individual with apparently controlled HCV infection suggests the usefulness of the strategy in characterizing and then producing antibodies that may be useful as therapy for the disease.
Families Can Provide a Shield Against A Child’s Initial Drug Use.
To investigate how various risk and resiliency factors interact with gender and ethnicity to impact substance use, researchers surveyed 609 students in the southwest United States. The risk factors studied were: family stress, unsafe neighborhoods, and parental substance use. The resiliency factors included: good family relations, a family that is not permissive, and high religiosity. The researchers found that a lack of resiliency factors were highly predictive of past month substance use, having received a drug offer, and acceptance of the offer. Both risk and resiliency factors affected age of initiation and the lifetime number of drug offers, with low resiliency Mexican-American females, African-American males, and European-American males receiving the most drug offers. Not surprisingly, those with low resiliency and high risk were likely to have started using drugs at earlier ages. Among males, risk factors were directly connected with substance use and the effect of resiliency factors was mediated by age of first use, whereas for females resiliency factors played a much greater role. These results suggest that for maximum effect substance use prevention efforts should focus on building resiliency prior to first drug use, particularly for males.
Drug Users in Communities with Low HIV Rates More Likely to Engage in High-risk Behaviors.
Researchers compared HIV-related risk behaviors among more than 12,000 intravenous drug users (IDUs) in 22 communities with various HIV seroprevalence (percent of people who test positive for HIV) rates. The researchers found that drug users living in low seroprevalence (5 percent or less) communities were more likely to engage in risky injection and sex-related behaviors than those living in communities with higher rates of HIV infection (moderate: 6 to19 percent, or high: 20 percent or more). IDUs living in sites with lower seroprevalence rates had the highest rates of having sex with another IDU during the past 30 days, and reported the highest level, 85 percent, of unprotected sexual acts. Rates of injection were about 2.5 times higher in high seroprevalence communities than in the low or moderate communities, yet more than 50 percent of drug users in low seroprevalence communities reported using syringes belonging to other people compared to the other sites. These findings highlight the importance of employing prevention methods in all communities, not just those with the highest rates of HIV infection, as drug use is now the major risk factor identified in new cases of AIDS in the United States.
Some Adolescent Smokers May Be Self-medicating.
Understanding why children begin to smoke may be key in developing effective prevention and treatment approaches. A recent study of adolescent smokers in a treatment program assessed inattention and hyperactivity symptoms and their relationship to smoking behaviors. The researchers found that adolescent smokers with frequent symptoms of inattention were using nicotine as a stimulant drug to help manage their symptoms.
Incentive to Work Helps to Keep Addicts Drug Free.
An experimental program has been successful in helping drug-abusing women stay free of drugs by paying them a salary to attend a work/training program. In the Therapeutic Workplace, women in drug treatment are hired and paid to either perform assigned jobs or to participate in job training. To link salary to drug abstinence, patients are required to provide drug-free urine samples to gain daily access to the workplace. Program participation nearly doubled the patients’ abstinence from opiates and cocaine, as determined by urine samples collected three times a week during the six-month study. Over the course of the program, 59 percent of the urine samples from the workplace women were drug-free, compared to 33 percent of the samples from a control group of women. Forty percent of the Therapeutic Workplace participants had drug-free urine samples on at least 75 percent of testing occasions; in contrast, only 10 percent of the control participants did so. This project confirms the results of many years of previous research that demonstrate that incentive-based treatment programs do result in decreased drug use. This program also exemplifies how research findings can be applied in real-world settings.
Story of Discovery - Understanding the Cannabinoid System
Marijuana is a drug that has been used for thousands of years, though it has not been until recently that we have begun to understand how it produces its many effects. In fact, it was not until the latter half of the 20th century that scientists discovered the active chemical component of marijuana and began to unravel the way in which this chemical works in the human body. The fact that marijuana is the most widely abused illicit drug with over 200,000 marijuana users seeking treatment for their marijuana addiction last year, is one of the major reasons why we need to continue to understand its allure, its consequences, and to determine the most effective ways to prevent and treat its use.
The quest for understanding how marijuana works began in the 1800s. During this era there was a trend in chemical research to seek out and assess active natural products. Plant extracts such as “morphine, cocaine, strychnine, and many others were purified and used in medicine.” (Mechoulam, Chemistry and Physics of Lipids, 2000) Cannabis, because of its use in India and China, was also investigated, but unlike many extracts from other plants, the structure of marijuana’s active ingredient made it extremely difficult to isolate. Through the 19th and first half of the 20th century there were numerous extracts reported, but the active ingredient of marijuana proved elusive.
It would not be until 1964 that marijuana’s active ingredient, delta-9-tetrahydrocannabinol (THC), was finally isolated in pure form. It would take another three years to determine THC’s exact chemical structure. It was this discovery that opened the door for numerous researchers to begin exploring how marijuana works in the brain to produce its psychoactive effects as well as to begin understanding how it produces its known detrimental effects which include disruptions in memory processes and the development of dependence.
Initially, it was believed by some that THC exerted its effects in the body because it is lipophilic, or fat soluble, which enables it to easily penetrate cellular membranes and enter cells. The idea was that the drug entered brain cells directly and once inside the cell was able to disrupt the cell’s normal activities. This was an unconventional idea because it was known that many other drugs of abuse, such as morphine and nicotine acted in the brain through their ability to attach to and activate naturally occurring receptor proteins on the surface of nerve cells. In 1988, this debate was settled with the discovery of a marijuana, or cannabinoid, receptor in the brain, “CB1.”
With this discovery, scientists were faced with answering the question of why the brain produces its own THC receptor? The presence of a naturally occurring cannabinoid receptor implies that the brain must produce endogenous cannabinoid-like chemicals, and if so, what do these chemicals do in the brain? Researchers were able to begin answering these questions in 1992 when they discovered anandamide, a chemical naturally produced by the body that has many similarities to THC. The discovery of this first endogenous cannabinoid was followed in 1993 by the identification of a second cannabinoid receptor, CB2, which is found predominantly on immune system cells.
With the identification of the CB1 and CB2 receptors and anandamide a previously unknown receptor/neurotransmitter system in the brain had been discovered. With these breakthroughs, research has been advancing at a rapid pace. Scientists have discovered interesting parallels between the cannabinoid receptor system and the well-studied, opiate receptor system. Research is revealing that the natural cannabinoid system has more far reaching effects than previously recognized as it is involved in cognition, memory, motor coordination, and pain. The presence of this newly discovered receptor system in the brain circuitry controlling learning and memory is yielding new insights into how marijuana disrupts memory traces. Additionally, recent research shows that there are connections between the cannabinoid system and the neuronal processes connected with relapse to cocaine abuse, lending further support to the commonality in the brain processes mediating addiction.
The discovery and characterizations of the cannabinoid receptors has also allowed scientists to begin to develop potential medications to treat those individuals addicted to marijuana. In 1994, researchers produced the first cannabinoid antagonist, SR141716A, which is able to block THC’s ability to activate the CB1 receptor. Preclinical and clinical research is suggesting that SR141716A blocks the high elicited by marijuana and may also be useful in preventing relapse to drug use. Further, this compound also shows indications of being able to prevent relapse to cocaine use.
Today marijuana-related research continues yielding valuable insights into the effects of THC on critical brain functions, such as cognition and memory, the role of the drug’s receptor system in addiction and relapse, as well as insights into the treatment of marijuana addiction. In addition, research regarding our own endogenous cannabinoids is providing us with a sense of the scope of their effects in our bodies and insight into the possible use of medications based on these chemicals for the treatment of pain, particularly types of pain which do not respond well to treatment with opiates. Finally, these insights are leading us to an overall greater understanding of neurobiology, memory, and immunity. They also provide us with proven strategies that can be employed to help us elucidate other systems.
In FY 2003 NIDA will expand its collaboration with the Substance Abuse and Mental Health Services Administration in developing its health services research portfolio to enable a more rapid translation of research findings into the delivery of substance abuse treatment and prevention services.
NIDA Budget Policy
The Fiscal Year 2003 budget request for the NIDA is $967,898,000, including AIDS, an increase of $77,960,000 and 8.6 percent over the FY 2002 level.
A five year history of FTEs and Funding Levels for NIDA are shown in the graphs below. Note that Fiscal Years 2000 and 1999 are not comparable for the Managerial Flexibility Act of 2001 legislative proposal.
One of NIH’s highest priorities is the funding of medical research through research project grants (RPGs). Support for RPGs allows NIH to sustain the scientific momentum of investigator-initiated research while providing new research opportunities. The Fiscal Year 2003 request provides average cost increases for competing RPGs equal to the Biomedical Research and Development Price Index (BRDPI), estimated at 4.0 percent. Noncompeting RPGs will be funded at committed levels which include increases of 3 percent on average for recurring direct costs.
Future promises for advancement in medical research rest in part with new investigators with new ideas. In the Fiscal Year 2003 request, NIDA will support 502 pre-and postdoctoral trainees in full-time training positions, the same number as in FY 2002. Stipend levels for NRSA trainees will increase by 4 percent over Fiscal Year 2002 levels.
The Fiscal Year 2003 request includes funding for 37 research centers, 289 other research grants, including 233 clinical career awards, and 137 R&D contracts. The R&D contracts mechanism also includes support for 17 contracts for the Extramural Clinical and Pediatric Loan Repayment Programs. Intramural Research and Research Management and Support receive increases of 11 and 9 percent respectively over FY 2002.
The mechanism distribution by dollars and percent change are displayed below:
