SCIENTISTS SEARCH BRAIN FOR CHANGES
FROM ADDICTION

September 27, 1994
Media Contact:Michael Purdy
Phone: (410) 955-8725
E-mail: mpurdy@welchlink.welch.jhu.edu

Scientists at The Johns Hopkins Medical Institutions and the National Institute on Drug Abuse (NIDA) are creating a first sketchy map of the places where addiction resides in the brain.

The map will improve scientists' understanding of the many psychological and biochemical changes brought about by drug addiction, perhaps opening new approaches to treatments for this complex problem.

To explore the changes drugs create in the brain, NIDA and Hopkins scientist Edythe London, Ph.D., showed volunteers who actively abuse cocaine pictures of items associated with drug use. London used positron emission tomography (PET) scans to monitor the subjects' brain activity during these exposures, hoping to observe changes that would indicate areas involved in drug craving.

Her preliminary studies show changes in the limbic system of the brain, a portion of the brain that is involved in emotion, learning and memory.

London presented her findings September 27 at a seminar on addiction for science writers. Among other presenters at the seminar:

George Uhl, M.D., Ph.D., also a Hopkins and NIDA researcher, whose research team has identified the molecular receptor sites that allow morphine, heroin and cocaine to stimulate the brain. They are working to develop ways to close off these receptors from drugs of abuse while still allowing the chemicals to continue to serve their regular functions.

Uhl also described a new mouse model for cocaine addiction. When the researchers inserted additional copies of the genes for the molecular receptors that cocaine targets, they observed changes in the behavior of the mice.

"We appear to have increased their interest in cocaine and possibly their potential for addictive behavior," says Uhl.

Mark E. Molliver, M.D. and Elizabeth O'Hearn, M.D. of Hopkins described their findings about the drug ibogaine, an hallucinogenic compound derived from the roots of an African shrub. Ibogaine has been touted anecdotally for its ability to curb cocaine addiction for months, easing withdrawal and eliminating drug craving.

Molliver and O'Hearn studied ibogaine's effects in animals to determine what parts of the brain this drug affects and whether it may be toxic. Their results show that, in the rat, ibogaine activates several regions of the brain, especially the cerebellum, an area of the brain thought to be involved in coordination, balance, posture, learning and habitual behaviors.

However, they also found that ibogaine kills a small percentage of nerve cells in the cerebellum - - a sign of neurotoxicity. The drug is still being considered for treatment since the brain appears to cope with a small amount of cell death. Researchers believe that other cells can sometimes compensate for the functions of cells that have died.

Undesired drug effects in man are difficult to predict based on animals. Studies of ibogaine in other species are underway to determine whether there is a safe and efficacious dose in humans.

To help balance ibogaine's potential effects on brain cells and its allegedly potent advantages as an addiction treatment, Molliver and O'Hearn are currently working on strategies to protect against the toxic effects of ibogaine.

Jack Henningfield, Ph.D., a researcher at NIDA and Hopkins, has developed methods for scientifically assessing the physical and psychological cravings felt by drug addicts.

Some craving, Henningfield explains, relates to the physical withdrawal symptoms created by a drug's effects on the body's biochemistry.

"Other cravings that have only recently become objectively measurable through our work relate to the positive mood states drug users expect to experience while using their drugs," says Henningfield.

Being able to objectively compare the cravings created by different addictions may help scientists learn more about those addictions and the best methods for treating them.


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