Temple Times Online Edition
    JANUARY 19 , 2006
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Temple center awarded new $4.7M grant from NIH to study drug abuse

While environment and psychology play important roles in drug abuse, understanding the little-known biological effects of marijuana, opiates and cocaine at a cellular and physiological level is just as — if not more — important in developing promising new treatments and prevention strategies, according to investigators at the Center for Substance Abuse and Research at the School of Medicine.

As one of only a few centers specializing in the basic science of drugs of abuse, CSAR recently received a $4.7 million grant from the National Institute of Drug Abuse to continue its groundbreaking work on mechanisms of addiction and how addictive substances interact with the nervous and immune systems.

“Eventually, as in the case of marijuana or morphine, the hope is to block the negative effects of the drugs while enhancing the positive, such as pain management,” said Martin Adler, Laura H. Carnell Professor of Pharmacology and director of CSAR.

Many of the center’s current investigations turn on how multiple drugs taken simultaneously affect the body, since addicts rarely ingest a single drug. Instead, by combining everything from alcohol to heroin to cocaine, often in a short period, they set off myriad complex internal biological changes, which can include immunosuppression — a reduced immune response, problems in regulating body temperature and shifts in the body’s perception of pain.

One novel explanation about why these reactions occur lies with chemokines, small signaling proteins that are produced by the brain and the immune system. CSAR scientists are studying how chemokines affect the activities of drugs in the nervous and immune systems, significantly altering the body’s natural responses.

In one example of this process, CSAR researchers are examining the role of opioids and their interaction with chemokines to understand why one-third of those infected with HIV are also intravenous drug users.

“We asked ourselves whether the coincidence is due solely to use of contaminated needles, or whether the drugs themselves are also to blame,” said Toby Eisenstein, co-director of CSAR.

“Findings by CSAR scientists Thomas Rogers, Lee Liu-Chen and Earl Henderson show that the drugs alter the chemokine receptors for the HIV/AIDS virus, and in some conditions, enhance HIV replication.

Other work by the Temple researchers has shown that certain chemokines can block the pain-relieving effects of morphine on the body. These findings provide clues as to how scientists might eventually fine-tune drugs, modifying both pleasurable and problematic effects of legal and illegal drugs.

Other ongoing CSAR studies are measuring the impact of drug withdrawal on the human immune response.

“We want to see whether symptoms during an addict’s withdrawal — such as chills or shakes — might actually be connected to immunosuppression, which leaves the immune system more vulnerable to illness and disease,” Eisenstein said. Examining this brain-immune system connection may help doctors to anticipate and better treat symptoms of withdrawal from abused drugs.

The uptick in interest in chemokines as a link between the brain and immune system has led Adler to theorize that the proteins will eventually be considered on a par with neurotransmitters, the discovery of which revolutionized treatment for depression.

“Much of this is brand-new research,” he said. “In many ways, we’re just at the beginning. Perhaps in seven to eight years we will understand the connections. But I think we’re onto something big.”

- By Ilene Raymond