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Researchers Awarded $3.69M to Study Genetics Mediating Response to THC

They'll look to identify genetic differences in brain effector signaling pathways.

Megan Mulligan, PhD, and Bob Moore, PhD.
Megan Mulligan, PhD, and Bob Moore, PhD.
Courtesy UTHSC

Researchers at the University of Tennessee Health Science Center have received a five-year grant totaling $3.69 million from the National Institute on Drug Abuse to study how genetic differences influence behavioral and physiological responses to tetrahydrocannabinol (THC), the major psychoactive component in cannabis.

Increased legalization for medical and/or recreational use and more favorable public perspectives has led to an increased use of cannabis. At the same time, the amount of THC in cannabis and derived products has dramatically increased. Recognizing a current lack of research on how high levels of THC impact health and behavior, principal investigators Bob Moore, PhD, professor in the Department of Pharmaceutical Sciences, and Megan Mulligan, PhD, associate professor in the Department of Genetics, Genomics & Informatics (GGI), are conducting research to identify genetic differences in brain effector signaling pathways that mediate individual differences in response to THC.

Their research aims to identify genetic variation in cannabinoid receptor signaling pathways mediating the response to delta-9-tetrahydrocannabinol (THC). The team will use a pharmacogenomic screen in a recombinant inbred mouse population with different genetic backgrounds to help identify the specific genes and molecular signaling pathways responsible for variation in physiological response following exposure to a high dose of THC, similar to what may be present in current high-potency cannabis and derived products.

“This is the first screen for initial response to THC in a genetic population of any animals,” said Dr. Mulligan. “We are positive that we will be able to identify gene variants in cannabinoid receptor signaling and metabolic pathways that underlie differences in THC response in rodents, and we expect these responses and pathways to be similar in humans.”

The team, which includes co-investigators Byron Jones, PhD, professor in the Department of Genetics, Genomics and Informatics, and Xusheng Wang, PhD, associate professor in the Department of Genetics, Genomics and Informatics, hopes to make a significant impact in better understanding the genetic regulation of cannabinoid receptor signaling in the brain. The study’s findings will be important for future investigations into the impact of THC over the lifespan and in other biological systems beyond the brain.

“If the scientific community sees us having success in identifying how genetics regulates responses to THC, then this approach could be used as a screen to understand whole system effects of new drug candidates,” Dr. Moore said. “I hope it will bring a new approach to potentially identify unwanted side-effects of new therapies and guide medicinal chemists in the drug development effort.”

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