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NIDA Strategic Plan (Continued)
Strategy 2: Develop and Distribute Tools To Improve the Quality of Drug Abuse Treatment Nationwide
NIDA research has produced a number of effective medications and behavioral
treatments for addiction, though there is still much work to be done. Research
focused on the following areas will significantly improve how our Nation treats
addiction in future generations:
- Translating basic neurobiological and behavioral research
into new treatments;
- Ensuring that science-based treatments are translated for use
in community settings;
- Bringing scientific methods to the examination of traditional,
community-based treatments for addiction; identifying and
standardizing the "active ingredients" of those treatments;
- Understanding the medical consequences of drug abuse and
addiction and using that knowledge to develop new pharmacological
and behavioral strategies to deal with those consequences.
Scientific advances, particularly over the past decade, have catapulted both
our understanding of addiction and approaches to treating it. Research has, in
fact, come to define addiction as a chronic disease, for many people a recurring disease, characterized by compulsive drug-seeking and drug use that results from the prolonged effects of drugs on the brain. Both animal and human studies have demonstrated that chronic drug use changes the brain in fundamental ways that persist long after the drug use has stopped. By using advanced brain imaging technologies, we can see what we believe to be the biological core of addiction.
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The photo at left shows one example of how long-term drug abuse can dramatically alter the human brain. These PET (positron emission tomography)
images show levels of dopamine transporters in the brains of four different adults. Dopamine function is critical to emotional regulation, is involved in the normal experience of pleasure, and is involved in controlling an individual's motor function. The dopamine transporter is an important protein involved in the communication process among neurons that contain dopamine. In the images shown here, brighter areas reflect greater capacity for binding the dopamine transporter. The scan on the left is that of someone who uses no drugs; the next shows the brain of a chronic methamphetamine user who had been drug free for about 3 years when the scan was taken; the third is that of a chronic abuser of methcathinone (a drug of abuse similar to methamphetamine), who also had been drug free for about 3 years. The last image shows the brain of an individual newly diagnosed with Parkinson's disease, a disorder in which dopamine neuron degeneration is well documented. By comparing the control brain on the left with the other three, one can see the significant loss in the brain's ability to transport dopamine back into brain cells.
Data now suggest that every drug of abuse appears to increase the levels of
the neurotransmitter dopamine in the brain pathways that control pleasure.
It is this change in dopamine that we have come to believe is one fundamental
characteristic of all abusable substances and may be a central part of the
common essence or biological core of addiction.
This kind of fundamental knowledge, which NIDA-supported researchers
generate, gives us critical new insights into the long-term effects of drug
exposure on the human brain and can provide new targets and approaches
for the development of addiction medications.
It is of critical importance that we continue to expand our examination
of the brain processes involved in addiction. NIDA-supported research has
described in great detail some of the critical brain mechanisms involved in the
initial experiences of pleasure and reinforcement following drug use. Much of
that attention has been focused on one brain circuit at the base of the brain that runs from the ventral tegmentum to the nucleus accumbens. This circuit seems to be involved in the pleasurable experiences accompanying the use of all abusable drugs. In comparison, relatively little attention has been paid to the brain circuits and mechanisms involved in higher order cognitive and emotional processing of initial drug experiences, and little is known about the brain circuits subsuming the complex processes of addiction and, importantly, the transition process that underlies the conversion of a drug user from voluntary action to compulsive drug use. To effectively treat addiction and prevent relapse, we will need to have a better understanding of the cognitive factors and the corresponding brain circuits that are involved in addiction.
Given that the development of new and effective treatments for addiction is
both a national need and a NIDA priority, it is imperative that we capitalize
on recent research advances to rapidly bring new treatments to the clinical tool boxes of front-line clinicians who are treating addiction. Just like other chronic diseases such as hypertension, diabetes, and cancer, for which medications have been developed, drug addiction is a disease that merits medication for its treatment. We have already made great progress in bringing an array of useful tools to drug abuse professionals to treat addicted individuals, such as:
- the readily available nicotine addiction therapies;
- the most effective medications to date for heroin addiction, methadone
and LAAM (levo-alpha-acetyl-methadol, trademark ORLAAM);
- a new medication, buprenorphine, also to treat heroin addiction
(see box); and
- a number of notable standardized behavioral interventions, such as
cognitive behavioral therapies and contingency management, that
are effective in treating both adults and adolescents.
Buprenorphine: A New Treatment Option for Heroin Addiction
A substantial body of NIDA-funded research has laid out the
neurochemical details of how opiates, including heroin, produce their
analgesic and behavioral effects. Perhaps the most important work in this
area has characterized the receptors that opiate drugs bind to in various
parts of the brain, for this endeavor has led directly to the development
of buprenorphine, which may soon become the latest pharmacological
treatment for opiate addiction. While the ultimate decision about safety
and efficacy rests with the U.S. Food and Drug Administration, many
NIDA-funded studies support the safety and efficacy of this new agent
for treating opiate addiction.
NIDA-supported research has shown that the so-called mu opiate receptor
is responsible for the effects associated with morphine: analgesia, euphoria,
sedation, and respiratory depression. Buprenorphine has the ability to
bind to this particular receptor, but does not activate the receptor to the
same extent as the opiates do. Thus it is classed as a partial agonist. As a
partial agonist, buprenorphine does not produce the same high as heroin,
for example, and is less likely to cause respiratory depression, the major
toxic effect of opiate drugs. At the same time, buprenorphine leaves
the mu receptor unusually slowly, so its effects last much longer than
those of other opiates (methadone, for example). These properties
make buprenorphine a valuable addition to the clinical tool box for
the treatment of opiate addiction.
NIDA and its commercial partners are also developing the buprenorphine-naloxone combination tablet. As a partial mu agonist, buprenorphine has some potential for misuse. The combination of buprenorphine with the opiate antagonist naloxone would significantly reduce the potential of
this medication for abuse. In fact, if a heroin addict attempted to abuse
the combination product by dissolving and intravenously injecting it,
the individual would experience unpleasant withdrawal effects induced
by the naloxone. However, naloxone taken orally would not produce
these effects. The safety and effectiveness profiles for buprenorphine
and the buprenorphine-naloxone combination suggest they will be
valuable new tools for the treatment of opiate addiction, likely
administered through normal medical practice settings like
physicians' offices.
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What this new view of drug abuse means is that drug addiction, like heart disease, can be a serious, life-threatening disease that is both preventable through proper education and treatable with a combination of medications and behavioral treatments. And research has clearly shown that drug abuse treatment can reduce drug use. In addition, treatment can reduce drug-related criminal
behavior and the health and social costs of drug use and addiction.
When their input was solicited for this Strategic Plan, NIDA's constituents
recommended specifically that the Institute expand its efforts to push proven
advances in treatment into as many environments as possible across the Nation.
A major part of this effort will involve the National Drug Abuse Treatment
Clinical Trials Network, which is placing special emphasis on testing new
therapies (behavioral, pharmacological, and combination therapies) in a broad
range of environments to facilitate the widespread use of any therapies found
to be effective in clinical trials. NIDA envisions that, when fully implemented, the CTN will consist of 30 to 40 Regional Research and Training Coordinating Centers based in university medical and research centers, and that each Center will be linked in partnership with at least 10 community treatment providers that represent a variety of treatment settings and patient populations available in the region. Such diverse populations would include adolescents, patients with dual diagnoses, minority groups disproportionately affected by particular drugs, and patients in the criminal justice system. The CTN also will enable researchers to look at gender and racial differences in treatment efficacy, drug interactions in abusers of multiple substances, and the long-term efficacy of many treatment approaches.
To disseminate information as widely as possible, each Center, working with
its partner community treatment providers, will establish specially designed
clinical research training programs and clinical education programs for local
treatment providers. Because of the scope of the CTN, NIDA is confident that
it will create a new paradigm that will enable the quickest implementation of
new therapies and intervention strategies possible across the entire Nation.
In addition, technology transfer should be bi-directional; that is, seemingly
effective treatments already in use in the community should be scientifically
tested and standardized. The CTN can be an effective vehicle for this transfer.
The majority of research on drug abuse and addiction has focused on
understanding the factors that lead to drug use, on preventing initial use,
and on the development and treatment of the illness of addiction. In addition,
much has been learned about the ways in which behaviors and patterns of drug
abuse contribute to other public health consequences, particularly the spread
of infectious diseases such as HIV/AIDS, tuberculosis, and hepatitis. However,
in marked contrast to other addictions, particularly nicotine addiction and alcoholism, relatively little is known about the medical and health consequences for the individual who has been abusing illicit drugs over a prolonged time. At minimum, prolonged drug abuse is associated with poor nutrition, inadequate housing, and only occasional health care. Moreover, there are extensive data from animal studies suggesting that various drugs of abuse alter immune system functioning. Yet, little attention has been focused on what happens to people who use drugs for many years. In order to truly reduce the health consequences of drug abuse and addiction in this country, we need to address this research need. NIDA's CTN will offer outstanding opportunities both for conducting this research and for developing approaches to treat the medical consequences of drug abuse.
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