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Thomas Bannister, an assistant professor in the Department of Chemistry and associate scientific director in the Translational Research Institute at Scripps Florida, has been awarded more than $700,000 by the National Institute on Drug Abuse (NIDA). Bannister is the principal investigator for the five-year study to optimize newly discovered compounds to combat cocaine addiction. Chemists in the Bannister group discovered the compounds as part of an effort to find new classes of molecules capable of treating brain disorders.

“Long-term drug addiction can cause biochemical changes in the brain of the drug user,” said Bannister. “Unfortunately the changes can reinforce the addiction, making it much more difficult to resist the urge to relapse. Animal studies suggest that there may be ways to normalize the brain chemistry of long-term drug users and raise the odds for a successful recovery.”

The Bannister lab’s hypothesis is that drugs capable of selective interactions with a brain protein called the NOP receptor will be beneficial in addiction therapy. The main hurdle in testing this hypothesis has been that drugs known to interact with the NOP receptor also interact with opioid receptors, where drugs such as morphine, Oxycontin®, and Vicoden® act to provide both pain relief and unwanted addictive effects. Thus if these drugs were used for treating cocaine addiction, they could simply cause a different addiction, a trade-off that wouldn’t be particularly useful.

The key finding prompting the grant application was new chemistry that gave molecules increased selectivity for the NOP receptor over the opioid receptors.

“We found molecules that were biologically specific, acting only at the NOP receptor and having no opiate effects,” said Bannister. “We made these advances while receiving funding from a NIH/NIDA one-year “economic stimulus” grant, in collaboration with Claes Wahlestedt and co-workers at the University of Miami. Claes’s group used studies with mice to show that our selective new compounds were not addictive. They also found that drug-adapted mice, after taking one of our best lead molecules, consumed less cocaine than untreated mice.”

While many more studies are needed to see if such therapy can work in humans, the new grant represents a major step toward that objective.

“This grant will allow us to optimize the chemical and biological properties of these molecules and to extensively study their effects in the brain,” said Bannister. “The long-term goal is to develop an entirely new and effective method for treating cocaine addiction.”

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