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NIDA funds $3.69m study on role of genetics in response to THC

The study is the first to explore how genetic differences affect individual responses to THC.



Megan Mulligan, PhD, and Bob Moore, PhD are leading the study. Photo: Courtesy UTHSC
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Researchers have received a $3.69 million grant from the National Institute on Drug Abuse (NIDA) to study how genetic differences influence behavioural and physiological responses to tetrahydrocannabinol (THC).

Increased legalisation of medical and/or recreational cannabis and more favourable public perspectives has led to an increase in its use. At the same time, the amount of THC in cannabis and derived products has dramatically increased. 

Recognising a current lack of research on how high levels of THC impact health and behaviour, scientists at the University of Tennessee Health Science Center are hoping to identify genetic differences in brain effector signalling pathways that mediate individual differences in response to THC.

The team will use a pharmacogenomic test in mice with different genetic backgrounds to help identify the specific genes and molecular signalling 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 Megan Mulligan, PhD, associate professor in the Department of Genetics, Genomics & Informatics (GGI).

“We are positive that we will be able to identify gene variants in cannabinoid receptor signalling and metabolic pathways that underlie differences in THC response in rodents, and we expect these responses and pathways to be similar in humans.”

READ MORE: How does THC work in the body? Researchers share new scientific insights

The team hopes to make a significant impact in better understanding the genetic regulation of cannabinoid receptor signalling 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.

Principal investigators Bob Moore, PhD, professor in the Department of Pharmaceutical Sciences, added: “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.

“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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