March 5, 2008
HOUSTON - The Department of Veterans Affairs has awarded a research grant to Frank Orson, M.D., Medical Care Line staff physician and principal investigator, Therese Kosten, Ph.D., Research Service Line co-investigator, and Thomas Kosten, M.D., senior advisor on Substance Abuse based in the Mental Health Care Line at the Michael E. DeBakey VA Medical Center (MEDVAMC) to develop an improved cocaine vaccine.
Substance abuse and addiction cause enormous problems on a global scale; impacting livelihoods and relationships, reducing productivity, increasing medical costs, and causing economic losses, health problems, and injuries. Statistics reveal one in eight human beings is likely to suffer from substance abuse or addiction at some time in their lives. Many more lives are ruined by the bystander impact of drug abuse on family members and friends. Increased violence, despair, loss of income, emotional trauma, and the destruction of family relationships are all consequences of drug abuse.
While substance abuse affects society as a whole, veterans and their families are particularly hard hit by this health problem. Military service, particularly in times of war, can increase the frequency of post-traumatic stress disorder (PTSD) and with this increase, come increased problems with substance abuse. In a 2002 survey, at least six percent of the total veteran population was found to have utilized illicit drugs in the previous year. This was predominantly among the younger age groups: 18 to 25 (30 percent) were more likely to have used an illicit drug in the past year than veterans aged 26 to 54 (12 percent) and veterans aged 55 or older (two percent).
“Development of the vaccines proposed by this research could have significant positive impact for our nation’s veterans. Acute withdrawal typically lasts a week or less for most drugs of abuse, but protracted withdrawal symptoms last months, and these protracted symptoms include sleep problems, mild depression, anxiety, irritability, and inability to concentrate,” said Orson. “Relapse to drug dependence most commonly occurs during the first several months after completing withdrawal treatment. During this time, there is a marked increase in drug craving can occur from even a single exposure to the abused drug. An effective vaccine will induce antibodies that bind to the drug of interest. Because antibodies do not cross the blood-brain barrier, the antibodies inhibit drug entry into the brain by retaining it in the circulation. As a result, the antibodies can block the induction of drug craving and reduce the likelihood of relapse to substance abuse.”
Also an associate professor in the Departments of Medicine-Clinical Immunology, and Immunology at Baylor College of Medicine, Orson received his medical degree from Baylor College of Medicine. His research interests also include genetic immunization for infectious disease (HIV and influenza) and for allergic inflammation.
The goal of this research is to develop safe and effective vaccines for drug addictions, specifically cocaine, but the results of this work may be directly applicable to other addictions, such as nicotine, methamphetamine, and heroin.
“Ideally, when a vaccinated individual uses the drug, the characteristic increase in drug cravings called drug reinforcement will be diminished or completely blocked by the antibody,” said Therese Kosten. “This decrease in the drug’s reinforcing effects may discourage patients from trying the drug again.
Therese Kosten is also an associate professor at Baylor College of Medicine. She received a received a doctorate in Psychology from Yale University. Her clinical and research interests focus on the neural and pharmacological bases of addiction with specific emphasis on dopamine and norepinephrine in the mesolimbic area; the role of stress, particularly early life stress, in vulnerability to addiction and post-traumatic stress disorder; sex differences in stress and addiction; and strain differences in stress and addiction.
Previous studies have demonstrated promising effects in human subjects. However, only about 30 percent of the subjects achieved levels of antibody sufficient to block the physiological effects of the absorbed doses. This research effort is designed to improve the quantity and quality of responses to such vaccines.
This study brings together a group of investigators with substantial experience in substance abuse, vaccine development, and medication development in a focused effort to utilize this promising preliminary data to generate truly effective vaccines. Collaborating investigators include Berma M. Kinsey, Ph.D., assistant professor in the Department of Medicine at Baylor College of Medicine; Rana Singh, Ph.D. assistant professor in the Department of Neurology at Baylor College of Medicine; and David Jackson, Ph.D., principal research fellow in the Department of Microbiology and Immunology at the University of Melbourne.
“This is a very exciting new era of prevention just now opening up to VA health care professionals to help our veterans to avoid addiction problems,” said Thomas Kosten. “A new nicotine vaccine would particularly be useful in reducing smoking in the veteran population and in proactively treating long term health problems.”
Thomas Kosten is also the Jay H. Waggoner professor of psychiatry and behavioral sciences in the Menninger Department of Psychiatry at Baylor College of Medicine and research director of the Veteran Affairs National Substance Use Disorders Quality Enhancement Research Initiative. His work in the field of addiction has resulted in a series of ground-breaking vaccines and technologies.
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