Alcoholism and Addictive Disorders

In the 10 years since arriving at Baylor, Dr. Kosten and his research group have brought extensive resources to the College to address the problem of addiction. These include a unique, NIH-funded research center, multiple grants and contracts from the Veteran’s Administration, and a Department of Defense (DOD) National Consortium for developing medications for substance abuse that now links 11 medical schools and four active military bases across the United States.

Dr. Kosten has also recruited six new faculty members to the addictions program and built clinical research in depression, post-traumatic stress disorder and traumatic brain injury (TBI) at the Michael E DeBakey Veterans Affairs Medical Center (MEDVAMC). The TBI center has been markedly enhanced through Dr. Stuart Yudofsky’s faculty recruits in the new Division of Neuropsychiatry, which extends well beyond the MEDVAMC.

In addition, through his role as co-director of the Duncan Institute of Clinical and Translational Research (ICTR) and as a member of the Baylor College of Medicine Comprehensive Cancer Center, Dr. Kosten focuses attention on nicotine addiction, the most preventable cause of a wide range of cancers whose rates are still growing, especially among minority populations.

Recent funding challenges to basic science research and international clinical research in addictions have been partially met by strong collaborations with the University of Houston, University of Texas in Houston, MD Anderson Cancer Center, and Rice University. Financial support has come from the State of Texas through CPRIT, and from others, including the Helis Foundation and individual donors such as the Toomim, Hackett, Robertson, Orson, Hankamer and Waggoner families.

Much remains to be learned about addiction, including the following:

• What makes an individual susceptible?

• Why will one sibling never be tempted by alcohol while another struggles daily with addiction? What is the family connection?

• Are the underlying causes of addictions the same or are there significant differences associated with each?

Baylor investigators work diligently to find answers to these and other scientific questions, as well as developing new medication treatments. The division’s goals for the next five years are to:

• Become the world’s leading center in addiction treatment and research

• Support and build the faculty base needed to continue its world-class research and discovery process to a higher level, and

• Train the next generation of clinical innovators in addictions through fellowship, visiting scholar, and lectureship programs. We graduate seven trainees each year, many of whom have gone into successful academic careers in addictions.

To accomplish these goals, and to improve the quality of life for countless people affected by addiction, the division is focused on the following activities.

Vaccines – Dr. Kosten works closely with his wife, Therese Kosten, Ph.D., a Yale-trained psychologist and neuroscientist now on the faculty at the University of Houston. Her role there enhances an important partnership and enables their joint pre-clinical activity to move forward at a faster pace. Together, the Drs. Kosten have been involved in several treatment innovations. As a result of a large national clinical study with an earlier vaccine developed by the Kostens and conducted with Baylor as the lead site, they have now developed a new and much improved cocaine vaccine that will move forward into human studies here at Baylor. In collaborations with Baylor researchers including Frank Orson, M.D., Daryl Shorter, M.D., and scientists from several biotechnology companies, two new vaccines for amphetamines and heroin have also been developed for use in the United States and potentially world-wide. These vaccines are critical for international public health because they are effective and can be produced relatively inexpensively compared to other treatments. Cost-effective strategies are imperative in parts of the world where AIDS is spreading through drug dependency. A new recruit to our addiction program from Harvard, Xue Zhang, M.D., Ph.D. will be working in our vaccine program and potentially in our collaborations with China under Xiang Zhang, M.D., Ph.D. Dr. Xue Zhang has experience in neuro-AIDS and neuro-immunology, a rapidly developing field that will enhance our addiction vaccine work. The amphetamine vaccine should move to human studies before the end of this year and these studies will include Dr. Xue Zhang. The Chinese government has also expressed substantial interest in this new vaccine and has been working with Dr. Kosten through his position as distinguished professor of psychiatry at Peking University and advisor to the Chinese National Institute on Drug Dependence. He has held these positions in China for more than 20 years.

Human Pharmacology and Neuroimaging – The division’s human laboratory research serves to screen candidate pharmacotherapies for safety and for potential efficacy as treatments for cocaine, methamphetamine, opiate, nicotine, and alcohol dependence. Effects produced by relatively small doses of these abused drugs administered in laboratory studies can be extrapolated to provide estimates of the effects produced when patients use larger doses outside research contexts. Similarly, the results of potential treatments on the cardiovascular, subjective, and behavioral or reinforcing effects of the abused drugs in laboratory studies can be predictive for subsequent large outpatient clinical studies. These laboratory studies also allow the Kosten team to select the most appropriate and safe medication dosages for larger outpatient studies, and sometimes to identify the patients most likely to respond to these new medications based on human genetics. The team, which currently includes Thomas Newton, M.D., Richard De La Garza, Ph.D., Colin Haile, M.D., Ph.D., Chris Verrico, Ph.D., Luba Yammine, FNP, Ph.D. and Jin Yoon, Ph.D., has screened almost 50 medications over the past 20 years and discovered successful therapies for cocaine, opiates, nicotine, and alcohol use. At Baylor, we have also added human neuroimaging to our technologies for discovering and screening new medications for addictions treatment through the leadership of Ramiro Salas, Ph.D. This multidisciplinary approach has been extremely efficient and time-saving and is the team’s major mechanism for translating discoveries in animal studies into new treatments for humans.

Human Genetics and Neuroimaging – Many psychiatric conditions, including vulnerability to drug addiction, response to addiction pharmacotherapy, and potential for recovery, have substantial genetic influences. The Toomim Psychiatric Genetics Laboratory studies the genetics and epigenetic components of these diseases and processes. Studies are underway to find the pharmacogenetic components that may modulate the therapeutic response of several drugs for the treatment of cocaine, methamphetamine, opiate, alcohol and nicotine addiction, as well as the genetic components of the vulnerability to develop alcohol, cocaine, and other addictions. The team also is studying epigenetics of heroin use, sex differences in the vulnerability to cocaine addiction, and cocaine-associated abnormalities in brain structure and function using functional MRI. The Psychiatric Genetics Laboratory is under the direction of David Nielsen, Ph.D., an established researcher in the fields of genetics of addiction vulnerability and epigenetics, and the neuroimaging is under the direction of Ramiro Salas, Ph.D., one of the most productive investigators at the Baylor Core for Advanced Magnetic Resonance Imaging (CAMRI).

International Studies – Our international studies are located in Russia as well as China. The Russian studies in collaboration with the Pavlov Institute and University in St. Petersburg address two areas. The first is intravenous heroin addicts’ use of the implantable opiate blocker, naltrexone. These studies are critical in preventing the spread of AIDS through drug use and include the second area of other medications to control sexually transmitted HIV. Our heroin vaccine is highly relevant to these epidemics in Russia and is under development with international commercial collaborators. In China we not only have the pending amphetamine vaccine studies, but also under Xiang Zhang, M.D., Ph.D. (different from Dr. Xue Zhang above) we currently focus on nicotine dependence among those with severe mental illness such as schizophrenia. These studies have resulted in over one hundred publications and grant support not only from USA based foundations and the NIH, but also from the Chinese National Academy of Sciences, which typically matches any funds that we bring to China for research studies. These international collaborations offer great promise for spreading the Baylor footprint throughout the world perhaps through formal affiliations with these highly prestigious medical centers in China and Russia, where Dr. Kosten currently has a strong foundation for building.

Education and Training - Training in addictions spans the whole medical school curriculum from first to fourth year, the four years of the psychiatry residency and several special fellowship programs jointly supported by NIH, the VA and Harris Health. For all trainees we provide didactic training under Daryl Shorter, M.D. and a department-wide Grand Rounds program. These special programs now support up to seven advanced fellows who have completed residency training. Since fully half of psychiatric patients have significant substance use disorders, this training addresses a critical need.

In addition to Dr. Kosten, the Menninger Department of Psychiatry and Behavioral Sciences has successfully recruited other scientists from nationally known institutions to join the program of translational research and education in addiction. They include Tom Newton, M.D. and Richard De La Garza, Ph.D. from UCLA, David Nielsen, Ph.D. from Rockefeller University and the NIH, Colin Haile M.D., Ph.D. from Yale, and most recently Xue Zhang M.D., Ph.D. from Harvard.

In the future, we hope to continue to attract the very best scientists to Houston. Baylor and the division have special appeal for up-and-coming scientists who want to further their training in alcoholism and addiction under the guidance of a remarkable group of experts.

The continued robust development of the Division for Alcoholism and Addictive Disorders will greatly strengthen the Menninger Clinic’s capacity to advance psychiatric treatment locally, nationally, and internationally. The partnership between the Menninger Clinic and Baylor College of Medicine will speed the translation of research findings from the laboratory bench to the patient’s bedside, ultimately improving the lives of people touched by addiction in Houston and around the world.