Dr. Frank wins R21 award

The $429,000 award from NIDA advances the Frank lab’s ongoing work

James Frank, Ph.D., in July 2025 was awarded $429,000 from the National Institute on Drug Abuse for the project, “Illuminating tetrahydrocannabinol signaling in the brain’s reward circuitry with in vivo photopharmacology.”

The project will build on the Frank lab’s ongoing work, validating the ability of photoswitchable THC analogs (azo-THC) and derivatives that can be localized in cells or tissue using protein tags (PORTL-THC) to reversibly manipulate CBR signaling in cultured neurons and in vivo.

Dr. Frank previously developed a photo-switchable THC analog azo-THC that can be isomerized between active and inactive configurations using two different colors of light. This allows THC activity to be turned ON and OFF in a reversible manner. To enhance azo-THC’s spatial precision, they also developed THC photoswitch that can be targeted to specific cells or membranes using genetically encoded PORTL-THC. Preliminary results demonstrate the feasibility of these tools to reversibly control THC activity with light; however, their application has so far been limited to CBR-overexpressing cell lines. This project will validate the utility of these optical tools to modulate THC activity in neurons, and then map the local effects of THC in the mesolimbic circuit during behavior.