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Name: David H. Overstreet Birth: August 4, 1943; Martinez, California. Education: PhD in Psychobiology, University of California at Irvine, 1972; AB in Psychology, University of California at Berkeley, 1965. Experience: Research Associate Professor, UNC Bowles Center for Alcohol Studies and Department of Psychiatry, University of North Carolina at Chapel Hill, 1990-present, 1989 (Visiting); Associate Professor, School of Biological Sciences, Flinders University, Australia, l984-1990; Visiting Scholar, Department of Psychiatry, University of California, San Diego, l984-l985; Visiting Associate Professor, Department of Pharmacology, University of California, Los Angeles, l984-l985; Senior Lecturer, School of Biological Sciences, Flinders University, Australia, l980-l983, l976-l978; l973-l975 (Lecturer); Visiting Associate Professor, Department of Pharmacology, University of Arizona, Tucson, l979; Visiting Associate Professor, Department of Pharmacology, University of California, Los Angeles, l979. Family: Married to Judy Overstreet, who works in the Department of Psychiatry. They have five children (ages 20-34) and 7 grandchildren.

From the stacks of scientific papers on his desk at his laboratories at the UNC Bowles Center for Alcohol Studies, to his white lab coat and deliberate, thorough manner of communicating, Dr. David Overstreet appears very much the traditional scientist. When visiting him at his laboratory to discuss his research in alcohol, one expects to hear about traditional scientific subjects, such as operant conditioning of alcohol drinking or the biochemistry of alcohol's effects in the brain. Instead, Dr. Overstreet opens the conversation by extolling the virtues of a Chinese herbal tea used as a hangover remedy and antidote for alcohol intoxication: "The Chinese have used this herbal tea, which they call the 'drunkenness dispeller,' for hundreds of years to reverse alcohol intoxication. We should not overlook such a wealth of experience as we seek in our laboratory to identify compounds that could counter alcohol's detrimental effects."

Dr. Overstreet is particularly interested in identifying compounds that lessen the craving for alcohol. Such medicines might one day prove useful in combating alcoholism by diminishing alcoholics' urge to drink. Working with Dr. Amir Rezvani, also of the UNC Bowles Center for Alcohol Studies, and Dr. David Lee of the Research Triangle Institute, Dr. Overstreet found that injections of the Chinese herbal preparation NPI-028the 'drunkenness dispeller' ingested as a tea by practitioners of Chinese herbal medicinereduced alcohol intake in rats genetically bred to prefer alcohol. Purified component extracts of NPI-028 exhibited the same effect. In one experiment, rats had continual access to food and water, but alcohol access was limited to 1 hour per day.

Dose-Dependent Effects of NPI-028 on Alcohol Intake in Fawn-Hooded Rats Maintained on a Limited Access (1 hr) Schedule. After rats were adapted to the protocol they received intraperitoneal one of the two doses in counterbalanced order. *p < 0.05; **P < 0.01, from baseline. Effects of NPI-028 (1 g/kg, ip) or Saline (1 mg/kg, ip [control]) on Blood Alcohol Levels. The rats received intraperitoneal injections of NPI-028 or saline 30 min prior to an ip injection of 2.5 g/kg ethanol. Blood was taken 1, 3, and 5 hr after the ethanol injection from the tip of the tail and analyzed by gas chromatography. There were no differences between the two groups at any time point.

A dose of 1.5 g/kg NPI-028, which does not affect heart rate or body temperature or cause behavioral depression, eliminated alcohol intake in animals that had consumed 0.6 g/kg/hr alcohol prior to administration of NPI-028 (See Figure 1 at left). NPI-028 reduced alcohol intake without affecting water intake and at much lower doses than those required to decrease food intake. Results suggest that the effects of therapeutic doses of NPI-028 are relatively specific to alcohol and do not extend to other liquids or foods.

Does NPI-028 simply affect the body's ability to metabolize alcohol, or does it act on the brain's circuitry to dampen alcohol-associated reward and, possibly, alcohol craving? Dr. Overstreet and his colleagues ruled out an effect of NPI-028 on alcohol metabolism by showing that blood levels of alcohol were virtually indistinguishable between rats given NPI-028 and those given an inactive control solution instead of NPI-028 before they were administered alcohol (See Figure 2 at left). They speculate that NPI-028 may act on the brain's serotonin system to affect alcohol craving. An effect of NPI-028 on alcohol craving is consistent with Dr. Overstreet's recent finding that NPI-028 reduces alcohol consumption even in alcohol-preferring rats whose alcohol "craving" was elevated due to alcohol deprivation.

Dr. Overstreet and his colleagues recently found that NPI-028 given either orally or as an intramuscular injection reduced alcohol intake in alcohol-preferring African green monkeys. The discovery of a suppressant effect of NPI-028 on alcohol drinking in this primate species increased the researchers' confidence that NPI-028 will also reduce drinking in alcohol-dependent humans. Like the encouraging results with the African green monkeys, the vast human experience with NPI-028 as an herbal treatment for alcohol-related maladies points to its promise in fighting alcohol addiction. The tea's use in Chinese medicine is restricted primarily to reducing the intoxicating effects of alcohol and to alleviating hangover symptoms; in Chinese medicine, the herbal tea is not used to prevent or decrease alcohol drinking. Whether or not NPI-028 actually reduces alcohol drinking in alcoholics awaits confirmation in clinical trials, which may start as early as next year.

Dr. Overstreet hypothesizes that an herbal approach to combating the urge to drink may be more likely to succeed in some alcoholic patients than the traditional medical approach of administering pills or injections. "Scientific research has shown us that alcoholism is a disease," says Dr. Overstreet. "Whether we like it or not, though, many peopleincluding some suffering from alcoholismresist the characterization of alcoholism as a disease and may not like the idea of treating it by taking an injection or a pill. An herbal remedy such as the 'drunkenness dispeller' tea may be more acceptable to some people." In addition, herbal remedies may produce fewer noxious side effects than some of the Western medicinal treatments being developed for or currently used to treat alcoholism. For example, naltrexone (ReVia), the only medication approved to date by the US Food and Drug Administration for the treatment of alcoholism, causes nausea in many patients.

NPI-028 appears, based on the rat and monkey data, to possess characteristics not shared by other compounds that show promise in treating alcoholism. First, NPI-028 is extremely well-tolerated in rats and monkeys, and even very high doses do not cause toxic effects in animals. Second, repeated use of NPI-028 does not appear to lead to tolerance, in which the response to the drug diminishes with chronic or repeated administration. NPI-028 maintains its effectiveness in reducing alcohol intake even after it has been used repeatedly.

Dr. David Overstreet (left) of the Center for Alcohol Studies was recently awarded a prize for his research into herbal medicines. Edzart Ernst, Professor of Complementary Medicine at Exeter University and Chairman of the Competition, presented Dr. Overstreet with the 1997 Annual Scientific Award in Complementary Medicine at a ceremony in December held at the Rougemont Hotel in Exeter, England.

Dr. Overstreet and his colleagues are now isolating individual herbs comprising the herbal mixture of NPI-028 in an attempt to characterize the effects of the individual herbs on alcohol consumption. They hope to gain insight about the mechanism by which NPI-028 and its components affect alcohol drinking in order to develop more effective treatments for alcoholism. For example, administration of a combination of substances that affect alcohol-related behavior through distinct mechanisms might produce a more profound reduction in alcohol craving than either substance alone. A combination remedy comprised of naltrexone, which affects the brain opioid system, and NPI-028 or its components, hypothesized to affect the brain serotonin system, may act synergistically to treat alcoholism more effectively than naltrexone or NPI-028 administered alone.

Dr. Overstreet's work with NPI-028 has been honored with the 1997 Annual Scientific Award in Complementary Medicine, presented at a ceremony held in Exeter, England, by Edzart Ernst, Professor of Complementary Medicine at and traditional Western science. His work has advanced the state of knowledge regarding compounds potentially of huge therapeutic value. "What is especially exciting about the Chinese herbal research," says Dr. Overstreet, "is that the use of these substances in alcoholics is possible in the near future. Right now, an investigator in Boston is conducting clinical trials with kudzu, one of the major plants comprising NPI-028. And the Minnesota Center for Addiction and Alternative Medicine Research may soon be conducting trials on NPI-028. Thus, it may be possible to work with the same groups to test the pure compounds we have isolated from NPI-028."