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Research Provides Further Evidence for the Mechanism of Action Underlying Hythiam’s Prometa Treatment Program

PROMETA Reverses GABA Receptor Dysregulation in Methamphetamine Dependent Rats with Increased Anxiety During Withdrawal

LOS ANGELES--(BUSINESS WIRE)--Hythiam, Inc. (NASDAQ:HYTM), announced today the presentation of data further supporting a mechanism of action underlying the company’s PROMETA Treatment Program. Dr. Sheryl Smith, a leading researcher in the field of neurosteroids, presented her findings earlier this week at the 2008 Society for Neuroscience annual meeting taking place in Washington, D.C. through November 19th. The study focused on methamphetamine dependent rats and highlighted a methamphetamine induced increase in the alpha-4 and delta subunit expression of the GABAA receptor that has been associated with states of hyper-excitability and anxiety. Receptor dysregulation of the alpha-4 subunit has previously been associated with alcohol, methamphetamine and neurosteroid withdrawal. The current study shows that a component of the PROMETA Treatment Program (PROMETA) reverses the increase in both alpha-4 and delta subunit expression in chronic methamphetamine treated rats.

The study included the acoustic startle behavioral response evaluation. The acoustic startle is an involuntary, reflexive whole body movement triggered by a loud noise that reflects increased anxiety. An exaggerated startle response, occurring during methamphetamine withdrawal, was also reversed.

Sheryl S. Smith, Ph.D. has published over 50 papers in peer-reviewed journals and 12 reviews/chapters, and has presented her work at 30 national and international meetings. Her work has been funded by NIH, National Institutes on Alcohol Abuse and Alcoholism, and the United States Air Force as well as by pharmaceutical companies such as Astra-Zeneca, Merck, and Lundbeck.

“Craving, anxiety, and stress are associated with substance dependence and relapse,” said Gary Ingenito, M.D., Ph.D. and Hythiam’s Senior Vice President of Scientific Affairs. “Withdrawal is a trigger for one or all of these. The current data from Dr. Smith builds upon her previous findings, and the literature regarding the structural changes that occur in the GABAA receptor with substance abuse and withdrawal. We now have both electrophysiological and behavioral evidence showing that a component of PROMETA reverses the increased expression of alpha-4 and delta subunits of GABAA receptors, and relieves increased anxiety associated with methamphetamine withdrawal. The ability to translate findings at the cellular level into behavioral effects validates the mechanism of action for PROMETA, as well as the potential therapeutic value.

“Dr. Smith’s work also provides additional insight into the use and efficacy of PROMETA as it relates to Dr. Raymond Anton’s recently completed double-blind, placebo controlled study in humans with alcohol dependence. Results showed that patients demonstrating relatively more symptoms of substance dependence withdrawal had a superior response to PROMETA. This is consistent with the current findings from Dr. Smith’s presentation since withdrawal, stress, anxiety and craving increase dysregulation of the GABAA receptor, which is a key target of PROMETA. Alleviating cravings during the early treatment of substance dependence can allow the patient to be more engaged in psychosocial therapy, a critical requirement for long-term abstinence,” Dr. Ingenito concluded.

Sheryl S. Smith, Ph.D., is a Professor of Physiology and Pharmacology at the State University of New York Medical Center, in New York City. She is a member of the Neuroscience Society and serves as an ad hoc grant reviewer on various National Institutes of Health (NIH) study sections. She is currently a manuscript reviewer for numerous journals, including the Journal of Neuroscience, the Journal of Physiology, and Neuropharmacology. She has recently received special recognition with an award for innovation from the State of New York Research Foundation. Her current research interest is the role of chronic neurosteroid exposure in altering the inhibition in the brain with emphasis on plasticity of the GABAA receptor. She also teaches endocrinology and medical neuroscience at SUNY Medical Center in New York City.

About the PROMETA® Treatment Program

Hythiam's PROMETA Treatment Program is designed for use by health care providers seeking to treat individuals diagnosed with dependencies to alcohol, cocaine or methamphetamine, as well as combinations of these drugs. The PROMETA Treatment Program includes nutritional supplements, FDA-approved oral and IV medications used off-label and separately administered in a unique dosing algorithm, as well as psychosocial or other recovery-oriented therapy chosen by the patient and his or her treatment provider. As a result, PROMETA represents an innovative approach to managing alcohol, cocaine, or methamphetamine dependence that is designed to address physiological, nutritional, and psychosocial aspects of the disease, and is thereby intended to offer patients an opportunity to achieve sustained recovery. To learn more, please visit

About Hythiam®

Hythiam, Inc. provides through its CatasysTM offering, behavioral health management services to health plans, employers and unions through a network of licensed and company managed healthcare providers. Catasys offers integrated substance dependence solutions built around the patented PROMETA Treatment Program for alcoholism and stimulant dependence. The PROMETA Treatment Program, which integrates behavioral, nutritional, and medical components, is also available on a private-pay basis through licensed treatment providers and company managed treatment centers. Hythiam also researches, develops, licenses and commercializes innovative and proprietary physiological, nutritional, and behavioral treatment programs. Hythiam does not practice medicine or manufacture, distribute, or sell any medications and has no relationship with any manufacturers or distributors of medications used in the PROMETA Treatment Program. For further information, please visit

Forward-Looking Statements

Except for statements of historical fact, the matters discussed in this press release are forward looking and made pursuant to the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect numerous assumptions and involve a variety of risks and uncertainties, many of which are beyond the company's control that may cause actual results to differ materially from stated expectations. These risk factors include, among others, limited operating history and lack of statistically significant formal research studies, the risk that treatment protocols might not be effective, difficulty in developing, exploiting and protecting proprietary technologies, intense competition and substantial regulation in the healthcare industry; and additional risks factors as discussed in the reports filed by the company with the Securities and Exchange Commission, which are available on its website at

Hythiam, Inc.
Investor Relations:
Hasmik Bulujian, 310-444-4333
Dan Klores Communications
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Tim Sullivan, 212-981-5234


Posted: November 2008