Mr. Chairman and Members of the Subcommittee, I am pleased to be here today to discuss
how science is providing us with unprecedented opportunities to develop more and improved
treatments for those suffering from the disease of addiction. The science I present
this morning will be particularly relevant to the Drug Addiction Treatment legislation
that is the topic of this hearing.
Given that drug abuse and addiction affects every American either directly or
indirectly with the economic burden alone for drug abuse estimated to exceed $109 billion
in the latest estimate, it is imperative that we utilize science to develop new and
improved approaches to alleviate the devastating effects of this disease.
Scientific advancs, particularly over the past decade, have catapulted both our
understanding and our approaches to addiction. Research has in fact come to define addiction as a chronic, and for many people reoccurring
disease characterized by compulsive drug seeking and use that results from the prolonged
effects of drugs on the brain. A variety of studies in both humans and animals have
demonstrated that chronic drug use does in fact change the brain in fundamental ways that
persist long after the individual has stopped taking drugs. By using advanced brain
imaging technologies we can see what we believe to be the biological core of addiction.
What you are seeing in this image (Figure 1) is dopamine
transporter binding in four different adults. Brighter colors reflect greater dopamine
binding capacity. The scan on the left is that of a non-drug user, the next is of a
chronic methamphetamine user who was drug free for about three years when this image was
taken, followed by a chronic methcathinone abuser who was also drug free for about three
years. The last image is of the brain of an individual newly diagnosed with Parkinson's Disease. When compared with
the control on the left, one can see the significant loss in the brain's ability to transport dopamine
back into brain cells. 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 data now
suggest that every drug of abuse --be it nicotine, heroin, cocaine, marijuana or
amphetamine--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 addictions and is at the biological core of
addiction.
This kind of fundamental knowledge which is generated by NIDA-supported researchers is
used by our Medications Development Program staff to develop new targets and approaches
for medications. For example, as reported just last week in the Journal Nature, NIDA-supported
scientists in collaboration with researchers from the Institut National De La Sante Et De
La Recherche Medicale in France applied basic research findings about dopamine and cocaine
addiction to develop and test a potential new compound for cocaine addiction. The
researchers have developed a compound, BP 897, that appears to reduce cocaine "craving" in animals. The selective
partial agonist BP 897 works on the D3 receptor, one of the known dopamine receptors found
on the surface of brain cells, that is thought to be involved in the reinforcing effects
of cocaine. The compound was found to reduce cocaine-seeking behavior in rats trained to
associate cocaine taking with a light. The light represents an environmental cue or
stimulus, which the rat learns to associate with cocaine administration, the same way that
the mere sight of drug paraphernalia can trigger craving in human cocaine addicts who have
been abstinent for years. The compound was found to block the cued response, thus bringing
us one step closer to having a medication for cocaine addiction.
Given that the development of new and effective medications for the treatment of
addiction is both a national need and a NIDA priority, it is imperative that we capitalize
on recent research advances like this to rapidly bring new medications to the clinical
toolboxes of front line clinicians who are treating addiction. Just as medications have
been developed for other chronic diseases, such as hypertension, diabetes, and cancer,
drug addiction is a disease that also merits medication for its treatment.
We have already made great progress in bringing quite 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), which I will discuss
in more detail shortly; as well as a number of notable
standardized behavioral interventions, such as cognitive behavioral therapies and
contingency management, that are effective in treating both adults and adolescents.
Although we are optimistic that science can help bring more effective treatments to the
Nation's forefront,
there is a tremendous national need to bring these medications to fruition at a quicker
pace and to increase access to treatment. When one takes into account that there are
approximately 810,000 persons in need of treatment for heroin addiction and only space in
the existing methadone clinic system for 180,000 patients, the need for expanding
treatment for this population takes on new light.
The need to bridge the treatment gap by developing new treatments that are accessible
to those in need is a point articulated strongly by the Institute of Medicine, as well as
the National Institutes of Health''s November 1997 Consensus Development Conference on the Effective Medical
Treatment of Heroin Addiction, among others. Methadone, the medication that has been shown
to have the most favorable impact on mortality, morbidity and the interruption of
drug-seeking behaviors is still inaccessible to many. An abundance of studies have also
consistently shown that methadone is highly effective in retaining in treatment a large
proportion of patients, reducing their intravenous drug use and criminal activity and
enhancing their social productivity. Despite the clinical success of medications such as
methadone, pharmacotherapy for the treatment of drug addiction has received far too little
attention, particularly from the pharmaceutical industry.
In an effort to stimulate the availability of medications to treat drug addiction,
Congress authorized (P.L. 99-570) a drug discovery and development program within NIDA. To
work with industry to perform the research and development necessary to secure FDA
marketing approval for new medications to treat drug addiction, NIDA established its own
Medications Development Division (MDD) in 1990, which is headed by my colleague, Dr. Frank
Vocci.
By funding research at every step of the complex medications development process; from
the chemical syntheses, and the biochemical, behavioral, pharmacological, and
toxicological testing, to the clinical trials that evaluate the safety and efficacy of
potential medications, NIDA offers pharmaceutical firms and academia the resources and the
technical assistance to perform the necessary next steps to bring a medication to market.
MDD also aggressively pursues ways to facilitate and accelerate the medications
development process. An additional economic incentive for anti-addiction medication
development can come from the Food and Drug Administration under the Orphan Drug Act
It was NIDA's MDD that shepherded through the final development of the Nation's most recent tool to combat
heroin addiction, LAAM. LAAM, like the better known medication methadone, stabilizes the
brains of heroin addicts by ameliorating craving for heroin and preventing withdrawal
symptoms. Treatment with methadone requires daily dosing, whereas LAAM is effective for up
to three days.
LAAM was approved by the Food and Drug Administration (FDA) in 1993 after an extensive
research cycle that began with the 1968 discovery that the analgesic LAAM might be a
potential treatment for heroin addiction. Clinical research on LAAM continued
intermittently throughout the 1970s, and 1980s. As LAAM was "off patent" for more than 20 years, no
private sector entity attempted to develop LAAM when it was determined that additional
clinical trials would be required. NIDA advertised and awarded a contract to a small U.S.
company, Biometrics Research Institute, to develop and submit a New Drug Application for
LAAM. This contract eventually resulted in the approval of LAAM by the FDA. Once the drug
was approved in July 1993, there were still many barriers to overcome. For example, LAAM
can only be distributed to clinics and hospitals that operate licensed narcotic treatment
programs. Clinics had to receive approval to dispense LAAM from Federal, State and some
local authorities. Also, to permit LAAM to be distributed to treatment programs, states
first had to schedule or reschedule the medication into a Schedule II status, allowing use
in existing treatment settings. States also had to develop treatment regulations that in
some cases took over four years to receive the necessary approvals. Given these factors,
it is not difficult to understand why, as of May 21, 1999 according to the FDA, of the 934
outpatient Narcotic Treatment Programs in the nation approved for maintenance and
detoxification treatment only 376 are approved to dispense LAAM. We estimate that 5000 to
6000 patients are currently receiving LAAM.
This short case scenario of the financial and time consuming challenges that were
overcome to bring LAAM to the market exemplifies why pharmaceutical companies do not want
to invest in anti-addiction medications. There are virtually no market incentives for
pharmaceutical companies to develop medications for drug addiction. In fact the
congressionally mandated 1995 Institute of Medicine Report, "The Development of Medications
for the Treatment of Opiate and Cocaine Addictions," states that the disincentives
for the pharmaceutical industry to become involved in anti-addiction medications far
outweigh the incentives. The cost of bringing any new drug to market is enormous,
according to the Pharmaceutical Research and Manufacturers Association. It costs anywhere
from $350 to $600 million, and generally requires 10 or more years of a company's investment, with only one in
ten candidate medications eventually being brought to market. Not only are pharmaceutical
companies hesitant to develop medications for market and financial reasons, but they are
fearful of the stigma that society will attach to them or their drugs if they were to
develop a compound for drug addiction, especially if the compound has other medical uses.
For example, methadone was first developed as an analgesic. When it was approved for
treatment of opiate addiction it became subject to additional layers of regulation and
became stigmatized. As a result, sales dramatically plummeted. The industry is well aware
of the problems encountered by medications such as methadone and LAAM. They want an
adequate return on their investment before deciding to enter a new area of drug
development. Unfortunately the majority of the factors they look at, including the size of
the market, the nature of third party reimbursement for drug abuse, the regulatory
requirements for development and approval, the clinical trials that need to be conducted,
and the regulatory barriers concerning how the product may be administered among others,
are seen as problematic to the company. The bottom line is, if we want pharmaceutical
companies to invest in anti-addiction medications, incentives must be provided to them to
stimulate their interest.
For our part, NIDA will continue supporting basic research, as well as researching and
developing the most effective treatments for the populations we are treating. We have
learned a lot about treating opiate addicts from the methadone and LAAM experience. We
have learned, for example that medications that are full agonists such as methadone and
LAAM are very effective in treating heroin addiction. They are also effective in helping
to reduce the spread of infectious diseases, such as HIV, and hepatitis through reduction
of injection practices. Research has also taught us that we need to develop medications
that will be readily used and accepted by the populations we are treating. These are some
of the reasons that we are working to bring other medications to the Nation's forefront - buprenorphine and
buprenorphine combined with naloxone.
Buprenorphine is a partial mu opiate receptor agonist with unique properties which
differentiate it from full agonists such as methadone or LAAM. Partial agonists exhibit
ceiling effects, meaning increasing the dose only has effects to a certain level, so it
will be well tolerated by addicts and have low value and desirability for sale on the
street. Naloxone has been added to buprenorphine to minimize its abuse potential,
particularly with respect to parenteral (intravenous) abuse. These factors make this
medication a prime candidate to be administered in less traditional environments, thus
potentially expanding treatment to populations who either do not have access to methadone
programs or are unsuited to them, such as adolescents. Just next month we will be
enrolling patients in a buprenorphine/naloxone office based treatment trial that will help
us better refine and establish best practices for administering this medication.
Buprenorphine and buprenorphine/naloxone (bup/nx) would not be a replacement for
methadone or LAAM, but yet another treatment option for both physicians and patients. Both
methadone and LAAM would continue to remain an important part of the treatment continuum.
Buprenorphine and bup/nx, however, could help reach new groups of opiate addicts, such as
those in the seven states that do not currently have methadone programs; those who may be
reluctant to enter a methadone program; and adolescents and new heroin addicts who are
unsuited to methadone. As in all forms of medicine, it is critically important to allow
physicians and patients to have access to as many forms of treatment as may be available,
and to chose the best match for each individual.
It is also important that physicians are knowledgeable about addiction and the
comprehensive approach required for treatment to be effective. As noted in the November
1997 National Institutes of Health Consensus Development Statement, non-pharmacological
supportive services are pivotal to successful treatment. Ongoing substance abuse
counseling and other psychosocial therapies, vocational rehabilitation, and other needed
medical and social services are essential for program retention and positive outcome.
NIDA will continue to work with health care professionals and to conduct trials of
buprenorphine products in varied environments, such as primary care and mental health
clinics, to expand treatment availability and to ensure the effectiveness of these
medications in real world settings. It should be noted, however, that neither of these
products have yet been approved by the FDA to treat narcotic addiction.
As with all medical conditions, science will continue to provide us with the best hope.
It is science that will help us develop even more novel approaches to treat addiction. Our
only other hope is that when these new treatments are developed and tested, they will
rapidly be provided to those who need them most.
Thank you for the opportunity to testify before this Subcommittee. My colleague and I
will be happy to respond to any questions.
