[Congressional Record Volume 148, Number 137 (Thursday, October 17, 2002)]
[Senate]
[Pages S10655-S10658]
From the Congressional Record Online through the Government Publishing Office [www.gpo.gov]




                 FDA APPROVAL OF BUPRENORPHINE/NALOXONE

  Mr. LEVIN. Mr. President, last week, the fight against heroin 
addiction took a major leap forward after a decade of struggle. On 
October 8, 2002, the Food

[[Page S10656]]

and Drug Administration, FDA, announced the approval of a new anti-
addiction drug, buprenorphine/naloxone, which, followed with the 
directives of a new law I authored along with Senators Hatch and Biden, 
makes a dramatic change in the way America fights heroin addiction. 
This new anti-addiction drug, developed under a Cooperative Research 
and Development Agreement, CRADA, between the National Institute on 
Drug Abuse, NIDA, and a private pharmaceutical company, has been the 
subject of extensive successful research and clinical trials in the 
United States. The new law, the Drug Addition Treatment Act of 2000, 
permits, for the first time, such anti-addiction medications to be 
dispensed in the private office of qualified physicians, rather than in 
a centralized clinic. That change can have a revolutionary reduction in 
the number of addicts, the crimes some of them commit, and the heroin 
related deaths which have occurred.
  This newly approved anti-addiction medication has already been in use 
in France, where significant success has been achieved in getting 
patients off of heroin, reducing drug-related crime and reducing 
heroin-related deaths. For example, user crime in France and arrests 
are down by 57 percent and there has been an 80 percent decline in 
deaths by heroin overdose.
  It is estimated that there are approximately 1 million individuals in 
the U.S. who are addicted to heroin. The new office-based system is a 
revolutionary change and will make our communities better and safer 
places to live. It will open the door to tens of thousands of 
individuals to get rid of their addiction, but are now unable to or are 
reluctant to seek medical treatment at centralized methadone clinics, 
where their appearance amounts to an announcement of their addiction 
and which for many addicts are difficult to get to for their once or 
twice a day use. According to a report by the Department of Health and 
Human Services, many individuals who want to get rid of their addiction 
will not go to centralized clinics, ``. . . because of the stigma of 
being in methadone treatment. . . .'' The report went on to say that 
HHS was:

     . . . especially encouraged by the results of published 
     clinical studies of buprenorphine. Buprenorphine is a partial 
     mu opiate receptor agonist, in Schedule V of the Controlled 
     Substances Act, with unique properties which differentiate it 
     from full agonists such as methadone or LAAM. The 
     pharmacology of the combination tablet consisting of 
     buprenorhine and naloxone results in . . . low value and low 
     desirability for diversion on the street. Published clinical 
     studies suggest that it has very limited euphorigenic 
     affects, and has the ability to precipitate withdrawal in 
     individuals who are highly dependent upon other opioids. 
     Thus, buprenorphine and Buprenorphine/naloxone products are 
     expected to have low diversion potential . . . and should 
     incerase the amount of treatment capacity available and 
     expand the range of treatment options that can be used by 
     physicians.

  The compelling need for this new system of treatment is borne out in 
some astonishing data. A recent study by the U.S. Office of National 
Drug Control Policy, ONDCP, released in January of this year, shows 
that illegal drugs drain $160 billion a year from the American economy; 
and that the majority of these costs, $98.5 billion, stem from lost 
productivity due to drug-related illnesses and deaths, as well as 
incarcerations and work hours missed by victims of crime. The report 
found that illegal drug use cost the health-care industry $12.9 billion 
in 1998. Commenting on the release of the study, ONDCP Director John P. 
Walters said:

       Drugs are a direct threat to the economic security of the 
     United States . . . and results in lower productivity, more 
     workplace accidents, and higher health-care costs, all of 
     which constrain America's economic output. Reducing substance 
     abuse now would have an immediate, positive impact on our 
     economic vitality. When we talk about the toll that drugs 
     take on our country, especially on our young people, we 
     usually point to the human costs: lives ruined, potential 
     extinguished, and dreams derailed. This study provides some 
     grim accounting, putting a specific dollar figure on the 
     economic waste that illegal drugs represent.

  Another recent study, released in September of this year, determined 
that the majority of drug offenders in our State prisons have no 
history of violence or high-level drug dealing. The study found that of 
the estimated 250,000 drug offenders in state prisons, 58 percent are 
nonviolent offenders. The authors concluded that these nonviolent 
offenders ``. . .  represent a pool of appropriate candidates for 
diversion to treatment programs . . . .'' They went on to say that 
``The `war on drugs' has been overly punitive and costly and has 
diverted attention and resources from potentially more constructive 
approaches.''
  Of the juveniles who land behind bars in State institutions, more 
than 60 percent of them reported using drugs once a week or more, and 
over 40 percent reported being under the influence of drugs while 
committing crimes, according to a report from the Bureau of Justice 
Statistics. Drug-related incarcerations are up and we are building more 
jails and prisons to accommodate them, more than 1000 have been built 
over the past 20 years. According to the July 14, 1999 Office of 
National Drug Control Policy Update, ``Drug-related arrests are up from 
1.1 million arrests in 1988 to 1.6 million arrests in 1997--steady 
increases every year since 1991.''
  In a September 3, 2001 interview with the New York Times, then-Drug 
Enforcement Administration nominee Asa Hutchinson underscored the need 
for drug rehabilitation for nonviolent offenders, saying that we are 
``not going to arrest [our] way out of this problem.''
  I believe that the system that we have finally put in place will 
effectively put America on the right road to fighting and winning the 
heroin addiction war. It has been a long and difficult road for over a 
decade. First, in providing the resources to help speed the development 
and delivery of anti-addiction drugs that block the craving for illicit 
addictive substances. Second, authoring a law that would allow for such 
medications to be dispensed in an office-based setting rather than 
centralized clinics, by physicians who are certified in the treatment 
of addiction. In 1996, the Senate adopted my amendment to the budget 
resolution to steer $500 million over 6 years to the National Institute 
on Drug Abuse, which resulted in substantial increases in funding for 
research conducted by the National Institute on Drug Abuse. Then, in 
1997, when Senator Moynihan and Senator Bob Kerrey joined me in 
convening a panel of experts to present their expert views at a Drug 
Forum on Anti-addiction Research, in an effort to assess the level of 
progress and needed support to expedite new anti-addiction discoveries. 
In October, 2000, the Drug Addiction Treatment Act, was enacted into 
law. Today, we are taking a giant step forward with the Food and Drug 
Administration's approval of this new anti-addiction drug, which will 
allow for the appropriate and long awaited, conventional, office based 
approach to addiction treatment in this country.

  The protections in the new law against abuse are as follows: 
Physicians may not treat more than 30 patients in an office setting; 
appropriate counseling and other ancillary services must be offered. 
Under this legislation the Attorney General may terminate a physician's 
DEA registration if these conditions are violated and the program may 
be discontinued altogether if the Secretary of HHS and Attorney General 
determine that this new type of decentralized treatment has not proven 
to be an effective form of treatment.
  This great success would not have been possible without the 
scientific genius, leadership and steadfast support of many 
individuals, including, Dr. Alan Leshner, who, during his 7-year tenure 
as Director of NIDA, energetically led the government initiated 
partnership that produced buprenorphine/naloxone for the treatment of 
heroin addiction; Dr. Frank Vocci, a brilliant scientist who heads up 
Medications Development at NIDA and whose tutoring has led me to a 
better understanding of the science of addiction; Dr. Charles Schuster 
of Wayne State University, a past director of NIDA who has conducted 
clinical trials on buprenorphine/naloxone, the results of which have 
been presented in testimony before Congress. Dr. Schuster has been my 
resource and my guide on this issue from the very beginning and his 
advice and expertise continues today; Dr. James H. Woods, Director of 
Drug Addiction Research Projects at the University of Michigan, has 
long been a progressive force in the area of addiction research, and 
has been an effective voice in the formulation of legislative policy in 
the area of addiction

[[Page S10657]]

both at home and abroad. Dr. Herbert Kleber, Professor of Psychiatry at 
Columbia University and one of the Nation's foremost experts on drug 
addiction and treatment, provided invaluable assistance to me in 
putting together this new system of treatment. Dr. Chris-Ellyn 
Johanson, President-elect of the College on Problems of Drug Dependence 
and Professor in the Department of Psychiatry and Behavioral 
Neuroscience at Wayne State University, has made major contributions to 
understanding the basis of the buprenorphine therapeutic effects in the 
treatment of heroin abuse and dependence; and Dr. Stephanie Meyers 
Schim, former president of the Michigan Public Health Association, who 
has helped us to understand that drug addiction is a public health 
problem that is in crisis and that our health policies should reflect 
this reality.
  In closing, I would like to thank those who too often go unnoticed, 
the Senate staff members who kept this legislation on track despite the 
many twists and turns and the unforeseen challenges along the way. My 
Deputy Legislative Director Jackie Parker, whose commitment and 
diligence in moving this issue was characteristically unwavering. Bruce 
Artim, who serves Senator Hatch on the Judiciary Committee and Marcia 
Lee of Chairman Biden's Subcommittee on Crime and Drugs were undeterred 
in their resolve to move all obstacles that came in the way of making 
this new system of treatment a reality.
  Finally, I ask unanimous consent that the remarks of Dr. James H. 
Woods of the University of Michigan, Dr. Chris-Ellyn Johanson and Dr. 
Charles R. Schuster of Wayne State University, and Dr. Herbert Kleber 
of the New York State Psychiatric Institute, along with a list of 
participants, be printed in the Record.
  There being no objection, the material was ordered to be printed in 
the Record, as follows:

 Dr. James H. Woods, University of Michigan, Press Conference on Food 
   and Drug Administration (FDA) Approval of Buprenorphine/nx (BUP), 
                            October 9, 2002

       There are a variety of reasons for the scientific and 
     medical excitement today celebrating the approval of 
     buprenorphine for the pharmacotherapy of narcotic abuse. It 
     fits in what I hope will be a succession of new therapies for 
     drug abuse that will be employed under The Drug Addiction 
     Treatment Act to change the way we view addictions and how 
     they may be treated.
       There are, of course, many different groups of individuals 
     who are responsible for this important day. We need to show 
     our considerable appreciation to Senators Levin, Hatch, and 
     Biden for their support for The Drug Addiction Treatment Act. 
     Having worked most with Sen. Levin, I know that he has been 
     long interested in the important problem of drug abuse. He 
     has visited us at the University to see firsthand what we 
     were up to in evaluating different, novel approaches to 
     pharmacotherapy of drug abuse. He has kept the problems of 
     developing these therapies in mind and has worked long and 
     hard to bring this legislation into being. I know the Senator 
     believes fervently that buprenorphine's approval is going to 
     produce some major changes in the treatment of narcotic abuse 
     because of the ways that it will be used in conjunction with 
     The Drug Addiction Treatment Act. I wholeheartedly agree and 
     I hope what we are seeing today with buprenorphine will be 
     replicated with increasing frequency in the future.
       In my opinion, we will see the individual physician taking 
     an increasingly important role in dealing with narcotic 
     addiction in a different way. They will be dealing with 
     individuals who would not otherwise present themselves for 
     the kinds of treatment currently available. Those who prefer 
     the privacy of individual physician treatment can be allowed 
     that privilege with this new medication for it is very, very 
     safe. When we consider that 5 of 6 narcotic abusers are not 
     in treatment, it is clear that this new approach to therapy 
     is sorely needed.
       We need to show our appreciation to the National Institute 
     on Drug Abuse and their efforts toward medications 
     development. Were it not for their support in developing 
     buprenorphine, we would not be having this meeting today. 
     They have supported strongly both the effort to move 
     buprenorphine along towards this drug abuse indication, and 
     related research toward the development of other much needed 
     therapies in the field of drug abuse. Thus, knowing a bit 
     about what they have in mind for the future, I think we will 
     be seeing more of these meetings.
       We need to thank the firm, Reckitt Benckiser, for 
     sponsoring buprenorphine. It was clear early in the study of 
     buprenorphine that it might have potential as a 
     pharmacotherapy. This has been demonstrated quite well. The 
     drug has been fascinating to opioid pharmacologists ever 
     since it was made public, and its interesting pharmacological 
     properties were described. Though some of its pharmacology 
     remains elusive to us, it is clear that we may have happened 
     upon just the right molecule for opioid abuse treatment. Our 
     Narcotic Center Grant at the University, funded by NIDA for 
     some 30 years, has had the objective of improving upon some 
     of the effects of buprenorphine. We have made and studied 
     extensively hundreds of chemical relatives and found many 
     compounds comparable to buprenorphine, but none superior to 
     it in safety or duration of action. Thus, we believe that 
     buprenorphine is a substance that will be the best of its 
     kind for this type of therapy.
       I appreciate the concert of effort that it takes to bring 
     this new type of attention to the problem of drug abuse. It 
     is only with the combined legislative, governmental, 
     pharmaceutical, and scientific efforts that these problems 
     will be dealt with effectively.
                                  ____


 Dr. Chris-Ellyn Johanson, Wayne State University, Press Conference on 
 Food and Drug Administration (FDA) Approval of Buprenorphine/nx (BUP)

       My name is Chris-Ellyn Johanson and I am a professor in the 
     Department of Psychiatry and Behavioral Neurosciences at 
     Wayne State University and the incoming president of the 
     College of Problems of Drug Dependence. When I joined the 
     Wayne State faculty in 1995, I was fortunate enough to become 
     a part of a research center at the University of Michigan, 
     headed by Dr. James Woods and funded by the National 
     Institute on Drug Abuse. This center is devoted to the 
     development of safer and better opiate drugs and has been 
     continuously funded by the National Institute on Drug Abuse 
     for over 30 years. My research has focused on trying to 
     understand how buprenorphine exerts its therapeutic effects 
     in the treatment of heroin abuse and dependence.
       I have been fortunate to work in collaboration with Jon-Kar 
     Zubieta, also from the University of Michigan, using state-
     of-the-art neuroimaging techniques in conjunction with 
     behavioral measures to understand the biobehavioral basis of 
     the therapeutic efficacy of buprenorphine. Our studies have 
     clearly demonstrated that because buprenorphine's unique 
     pharmacology as a partial mu agonist, it can block the 
     dependence-related effects of heroin-like drugs and in many 
     ways combines the characteristics of the agonist treatment 
     agent methadone and the antagonist treatment, naltrexone. 
     Further, its pharmacology makes it a drug with a long 
     duration of action and a remarkable margin of safety.
       So I am very pleased to be here today to welcome 
     buprenorphine into the armamentaria for the treatment of 
     heroin addiction. Not only will buprenorphine allow the 
     expansion of treatment options for clinicians, but because of 
     the legislation sponsored by Senator Levin to allow office-
     based practice for drugs such as buprenorphine, this option 
     will be available to an increased number of opiate-dependent 
     patients. I want to personally thank Senator Levin and his 
     staff for their efforts in promoting more rationale treatment 
     for heroin addiction. The Drug Abuse Treatment Act of 2000, 
     which allows qualified physicians to treat opiate addicts in 
     their office, brings the treatment of heroin addiction into 
     mainstream medicine. This will not only increase the 
     availability of treatment but will as well destigmatize it. 
     Without this legislation, buprenorphine's unique advantages 
     could not be effectively utilized.
       I would also like to thank Senator Levin and his staff on 
     behalf of the College on Problems of Drug Dependence. One of 
     the major goals of this scientific organization, which has 
     been in existence since 1929, is the development of safer and 
     more useful medications for the treatment of addiction, 
     including heroin dependence. Most of the scientists who have 
     been responsible for the development of buprenorphine are 
     members of this organization and have presented their 
     findings with buprenorphine at its annual scientific meeting. 
     Because of this, CPDD has been very involved in pushing for 
     the approval of buprenorphine and has been appreciative of 
     the help of Senator Levin in getting approval.
                                  ____


            Dr. Charles R. Schuster, Wayne State University

       My name is Charles R. Schuster and I am a Professor of 
     Psychiatry and Behavioral Neuroscience at the Wayne State 
     University School of Medicine.
       I am extremely excited by the news that the Food and Drug 
     Administration has approved the marketing of two 
     buprenorphine preparations, Subutex and Suboxone, for the 
     treatment of opiate dependence. These products are the first 
     to be available in a new model of office-based treatment of 
     opiate dependence allowed under the Drug Abuse Treatment Act 
     of 2000. We can thank Senator Levin for his incredible 
     thoughtfulness and tenacity in fighting to get this 
     legislation through Congress.
       One of the major advances that has been made in the past 
     several years by a joint effort between Reckitt-Benckiser 
     Pharmaceutical company and the National Institutes on Drug 
     Abuse/NIH is the development of buprenorphine for the 
     treatment of opiate addition. I am privileged to have had a 
     role in the development of this safe, effective treatment 
     both during my tenure as the Director of NIDA and 
     subsequently as a NIDA

[[Page S10658]]

     grantee. Under the auspices of a NIDA funded treatment 
     research project I have utilized buprenorphine as a 
     maintenance therapy and have been very impressed not only 
     with its effectiveness in curtailing heroin use, but as well 
     with its acceptance by patients who would not have considered 
     treatment with methadone. Thus this medication may reach 
     opiate addicts who currently are resistant to enrollment in 
     opiate maintenance programs that use ORLAAM and methadone. I 
     have letters on my desk from patients whose lives have been 
     turned around by the buprenorphine maintenance treatment we 
     have provided them. I have even more letters from opiate 
     addicted people who are asking where they can find such 
     treatment. Because of the approval by the FDA of two 
     buprenorphine preparations and the passage of the Drug Abuse 
     Treatment Act of 2000, it is now possible to give the answer. 
     Find a qualified physician in your area of the country and be 
     seen as a regular patient in their office receiving a 
     prescription for buprenorphine. Tragically, I see young 
     people every day who are in need of medications to ease their 
     need for heroin so that they can become invested in 
     rehabilitation activities that can return their life 
     trajectory to a normal, productive and fulfilling course. 
     Currently the available medications, methadone and ORLAAM, 
     are extremely useful but ensnared in regulations that grossly 
     limit their potential effectiveness. Having a safe, effective 
     narcotic preparation like buprenorphine that can be used by 
     qualified physicians for the treatment of opiate addition 
     that is unfettered by the methadone regulations is a major 
     advance in our ability to provide badly needed services in a 
     cost effective manner.
       I am very proud as a resident of the state of Michigan to 
     have Senator Levin as my representative in the United States 
     Senate. He and his staff have worked tirelessly to secure the 
     passage of the Drug Abuse Treatment Act of 2000. This 
     landmark legislation represents a major shift in policy in 
     how we view and treat the problem of opiate addition. This 
     advance in our policies regarding the treatment of opiate 
     addition has been a long time in coming. But thanks to the 
     efforts of Senator Levin, it has finally arrived. I join in 
     celebrating this achievement which has the potential for 
     providing significant help to those attempting to overcome 
     the ravages of opiate addition. Individuals seeking help for 
     their opiate addition do not have much political power and 
     are rarely heard in drug abuse policy debates. Fortunately 
     for them they have a compassionate and steadfast advocate in 
     Senator Levin.
                                  ____


 Remarks of Dr. Herbert Kleber at Press Conference on FDA Approval of 
                            Buprenorphine/NX

       Today marks an important milestone in the treatment of 
     substance dependence disorders. Buprenorphine, both in the 
     combined form with antagonist naloxone and in the mono-form, 
     have just been approved by the Food and Drug Administration, 
     the first therapies approved for in-office prescribing under 
     the Federal Drug Addiction Treatment Act of 2000. The path 
     has been a long and at times torturous one but a careful one. 
     It can hardly be described as a rush to market: my first 
     research paper on buprenorphine was published in 1988 and 
     colleagues had published earlier. During this decade and a 
     half we have learned much about this agent and it's potential 
     for the treatment of narcotic addition. I am very grateful 
     for the help from certain key senators, both in passing the 
     Drug Addition Treatment Act and for their continued 
     encouragement during this long and difficult process. Senator 
     Carl Levin of Michigan has been a special stalwart in this 
     process but the effort has truly been a bipartisan one with 
     Senators Orrin Hatch of Utah and Joseph Biden of Delaware 
     both playing active roles along with Senator Levin.
       The importance of this day, however, is much more than the 
     particular medications involved. Buprenorphine to be sure 
     should help in combating opioid dependence in formerly 
     underserved communities. It is estimated that there are up to 
     1 million opioid dependent individuals in the United States 
     of whom less than 200,000 are in treatment. The annual cost 
     to society of opioid addiction is more than 20 billion 
     dollars. Buprenorphine may increase the likelihood of people 
     who have not currently sought out treatment to do so, thus 
     reducing the enormous toll, both in health and in crime, that 
     addiction takes on society. Injecting drug users and their 
     sexual partners, for example, have become the largest new 
     group of individuals becoming HIV positive. While 
     buprenorphine is neither a panacea nor a magic bullet, it 
     has major advantages in terms of safety, duration of 
     action, and ease of withdrawal in comparison to existing 
     medications on the market. That plus the ability to be 
     treated in the privacy of the doctor's office are all 
     important advances.
       The major importance of the FDA approval and the Drug Abuse 
     Treatment Act, however, go well beyond the particular 
     medications and instead to how we think about addiction. 
     Papers by myself and my colleagues have emphasized that 
     opioid dependence as with other addictions is a chronic 
     relapsing disorder, not a character flaw, failure of will, or 
     lack of self-control. These drugs change our brains, changes 
     that can persist long after the individual has stopped taking 
     the drug and lead frequently to relapse. When a patient who 
     cannot stop smoking on his own seeks help from his physician, 
     he is seen as a patient who needs help and the physician will 
     respond with a variety of medications and behavioral 
     interventions. Likewise, it is my hope that with the advent 
     of these medications the treatment of opioid dependence will 
     be able to be mainstreamed. Individuals who are dependent 
     either on street opioids like heroin or on prescription 
     opioids will be able to receive help in doctors' offices and 
     medical clinics. They will hopefully one day be treated with 
     the same dignity with which we treat the patient trying to 
     give up smoking or the diabetic or the hypertensive, all 
     individuals that have chronic relapsing disorders involving 
     both physical and behavioral components.
       Addiction is initiated by a voluntary act but this initial 
     voluntary behavior is in many cases shaped by pre-existing 
     genetic factors and there are early brain changes, which may 
     evolve into compulsive drug taking less subject to voluntary 
     control. It is important to recognize, however, that drug 
     dependence erodes but does not erase a dependent individual's 
     responsibility for control of their behavior. Many patients 
     with other chronic illnesses fail to see the importance of 
     their symptoms and thus may ignore physician's advice, fail 
     to comply with medication, and engage in behaviors that 
     exacerbate their illnesses. While such patients may not be as 
     disruptive, demanding, or manipulative as alcohol or drug 
     dependent patients, the patterns of denial of symptoms, 
     failure to comply with medical care and subsequent relapse 
     are not particular to addiction. One thing, however, that 
     does separate addiction from other illnesses is the waiting 
     list for treatment throughout the United States which 
     contradicts assertions that addicted persons do not want 
     help.
       Compassion or sympathy is not the basis for the argument 
     that physicians should treat addicted individuals. Medically 
     oriented treatments can be quite effective. In addition, 
     addiction treatments have been effectively combined with 
     legal sanctions such as drug courts and court-mandated 
     treatments. Medical interventions should be taught in medical 
     schools and primary care residencies. If physicians develop 
     and apply the skills available to diagnose, treat, monitor, 
     and refer patients in the early stages of substance 
     dependence, there will be fewer late-stage cases.
       I have been involved in treatment and research with 
     substance dependent individuals for over 35 years, initially 
     at Yale University and the last decade at Columbia 
     University. In between I spent approximately 2\1/2\ years as 
     the Deputy Director of the Office of National Drug Control 
     Policy under Bill Bennett and the first President Bush. The 
     new era in office-based treatment of opioid dependence is a 
     worthy successor to efforts made by our Office back in the 
     early 1990's to expand the number of individuals in treatment 
     with substance dependence. My appreciation--and that of many 
     future patients--to the legislators and federal agencies that 
     made this possible.
       Thank you.
                                  ____


Press Conference Participants, FDA Approval of Buprenorphine/Naloxone, 
                        October 9, 2002, SR 236

       Senator Carl Levin.
       Senator Orrin Hatch.
       Dr. Frank Vocci, Director of the Division of Treatment 
     Research and Development, National Institute on Drug Abuse.
       Dr. Steven K. Galson, Deputy Director, Food and Drug 
     Administration's Center for Drug Evaluation and Research.
       Dr. Wesley Clark, Director, Center for Substance Abuse 
     Treatment, Substance Abuse and Mental Health Services 
     Administration.
       Dr. Herbert D. Kleber, Professor of Psychiatry and 
     Director, Division of Substance Abuse, Columbia University.
       Dr. James H. Wood, Professor, Department of Psychology and 
     Pharmacology and Director of Drug Addiction Research 
     Projects, University of Michigan.
       Dr. Chris-Ellyn Johanson, Professor of Psychiatry and 
     Associate Director of Substance Abuse Research, Wayne State 
     University.
       Dr. Charles Schuster, Professor of Psychiatry and 
     Behavioral Neuroscience, Wayne State University.

                          ____________________