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Novel Clinical Treatments for Addiction
With the new-found wealth of information about the molecular machinery underlying addiction
and withdrawal in various age groups, Farber scientists are now taking the research
to the next level: treatments for real people suffering from substance abuse.
One of the biggest needs is for novel detoxification regimens. Currently, an addict who
goes to a clinic for help quitting is typically given methadone, which is associated with a
high rate of relapse. As an alternative, Van Bockstaele’s team is investigating the use of
low doses of a drug (naltrexone) that blocks opioid receptors in the brain. While naltrexone
normally precipitates withdrawal, making it unappealing to addicts, very low doses
seem to act in an opposite way.
Van Bockstaele’s team has done a series of studies on an animal model of opiate addiction
to test the effects of the low-dose naltrexone regimen, and have seen withdrawal
signs decrease by 60 percent in the treated animals. The team has also measured
changes in receptors, signaling pathways and gene expression in the locus coeruleus neurons
that they are targeting.
“At the cellular level, we want to understand if this very low dose of naltrexone can diminish
the over-activation of locus coeruleus cells thought to underlie withdrawal. We have
preliminary evidence that it is somehow providing a protective effect,” says Van
Bockstaele. The work has direct clinical applications, she adds, because the drug is currently
on the market, and human clinical trials could begin soon. In fact, Jefferson’s department
of psychiatry and human behavior is presently working toward this goal.
“We’re hoping an addict on this regimen would not be so compelled to keep taking the
drug because he would no longer have the biological changes occurring in the brain that>
are associated with the negative symptoms of withdrawal,” Van Bockstaele says. “If the
addict doesn’t feel as badly, maybe he won’t go and seek the drug as much.”
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