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Changing mindsets | U.C. Davis Magazine


Accelerate drug development

One of the problems with developing new drugs based on psychedelics is how to weed out those that cause hallucinations before they go to human trials. The rodent head twitch test is considered a reliable predictor, but you can’t really ask a mouse if it’s hallucinating. This presents a bottleneck for the development of new drugs.

“We don’t have good ways to screen for neurological drugs on a large scale,” said Lin Tian, ​​professor of biochemistry and molecular medicine at UC Davis School of Medicine. Tests that could be performed in cell culture would allow faster screening.

Tian’s lab uses light-based technology to study chemical messengers and receptors that carry signals in the brain. After Olson gave a departmental seminar on drugs affecting the serotonin 2A receptor, the two labs began to collaborate.

Graduate students Jason Dong, Calvin Ly, and Lee Dunlap invented psychLight, a modified version of the serotonin 2A, or 5-HT2A, receptor with a fluorescent tag. When psychLight is engaged by a hallucinogenic drug, he changes shape slightly, causing his fluorescence to increase. Non-hallucinogenic compounds binding to psychLight cause a different fluorescence profile.

PsychLight can be used to rapidly screen large numbers of candidate molecules for the potential to cause hallucinations, in biochemical tests or in cell cultures. This approach can also be used to conduct basic research on brain signaling, which is fundamental to understanding the basis of psychiatric illnesses, Tian said.

“I’m very excited that drug discovery and basic science can be pushed by this technology,” she said.

Tian and former graduate student Grace Mizuno also founded a company, Seven Biosciences, which has an exclusive license from UC Davis to psychLight and related technology. Their goal is to accelerate drug discovery by creating a platform that pharmaceutical companies can use to rapidly screen compounds for their neurological effects.

Cannabis turns green

While Olson is working on analogs of psychedelic drugs, fellow chemistry professor Mark Mascal is working on analogs of cannabidiol, or CBD, one of the active components of cannabis.

Cannabis, like psychedelic drugs, is a Schedule 1 controlled substance under federal law, although its production, possession, and use are legal under California state law and some other states. CBD derived from the closely related hemp plant is legal under federal law if certain conditions are met.

A formulation of CBD, sold as epidiolex, is FDA-approved as a prescription treatment for severe seizures. CBD also has potential for treating metabolic syndrome, cognitive decline and muscle recovery after injury, Mascal said.