Sensor Tool Lights the Way for Non-Hallucinogenic Drug Development
Last week researchers at the University of California, Davis, published a study about a genetically encoded sensor called “PsychLight,” capable of detecting hallucinogenic compounds in the brains of mice and how those compounds bind to receptors.
“The most shocking thing was the fact that it worked, they didn’t think it would work the way they designed the sensor, but it was able to differentiate hallucinogens from non-hallucinogens based on the sensor,” said researcher David Olson, assistant professor in the Department of Chemistry and Biochemistry at UC Davis.
Olson said neuropsychiatry is moving away from traditions that once involved rectifying chemical balances in the brain and towards trying to modify neural circuits in the brain region in a specific way.
Hallucinogens hold the promise to treat disorders like depression, post-traumatic stress and substance abuse, and even others like dementia, traumatic brain injury and potentially headache disorders. However, they also contain hallucinogenic properties whose effects are not entirely understood.
“We can actually visualize the effects of drugs administered to rodents,” said Olson.
Before the PsychLight sensor was created, the best test for understanding the compounds that do and do not create hallucinogenic experiences in animals was for researchers to monitor rodent head twitch responses.
A rodent would rotate its head rapidly for 20-30 minutes after drug consumption and researchers were able to measure the hallucinogenic potential by marking the number of head twitches.
However, these studies were often time-consuming and the rodent studies looked largely at behavioral changes from the drug, not how well it binds to the receptor.
Olson said when the team put the PsychLight sensor in the brain of a rodent, they could watch it bind and activate in vivo, or in living behaving animals, and the sensor turned on at the same time that the rodent twitched its head.
“We wanted to be able to demo we could activate the sensor in an awake behaving animal and by correlating behavior effects with sensor activation how long the drugs take effect,” said Olson.
“It’s a very fast process, you can get an answer in a matter of minutes as opposed to days for a couple of compounds for mice,” he continued.
The confirmation educed by hallucinogens and non-hallucinogens, known as direct optimal read out of 5HT confirmation, can provide researchers insight into the potential behavioral effects of these binders for more than psychedelics, as a lot of important non-hallucinogenic drugs bind to this receptor.
The PsychLight tool is currently being used by academics and companies in the discovery process of identifying non-hallucinogenic compounds and for understanding serotonin biology, new medicines for brain disorders and non-hallucinogenic medicines.
One of those companies using PsychLight is Olson’s own biotech company which he co-founded, called Delix Therapeutics, which is creating hallucinogenic plasticity genetic compounds and non-hallucinogenic plasticity genetic compounds.
“Do you need the hallucinogenic effects, no, you can decouple the two, and I’ve been making chemical modifications to the structure of hallucinogenics to make them non-hallucinogenic, but still provide those therapeutic effects,” said Olson.
Olson said these new drugs could be like a new anti-psychotic or replace often unfavorable treatments like Selective Serotonin Reuptake Inhibitors, which are only effective for a small number of people as studies show a third of people won’t respond to these treatments.
“Now that we understand the pathophysiology better, we might actually be able to design therapeutic treatments and democratize this type of treatment so you can have a drug safe enough to put in your medicine cabinet,” said Olson.
Olson said the drugs would be more cost-effective than current mental health therapies, as they would be cheaper than paying for three days of therapy and multiple physicians. Current hallucinogenic therapies, such as psilocybin treatment, are offered at relatively few treatment centers, require lengthy days at the clinic and very few clinicians are properly trained to provide psilocybin assisted therapy. These factors could also exacerbate health inequities.
COVID-19 raised awareness for finding new medicines to treat mental health disorders, as there has been a rise in mental health conditions following the pandemic. Olson said about 20% of the population lives with mental disorders in the U.S., emphasizing the need to innovate and move the needle for new and better treatments.
Delix has been talking to larger pharmaceutical companies about potential partnerships and licensing opportunities, and Olsen said some are interested in this space and everyone is trying to figure out what the best bet would be going forward.
“We are unique in this space because the Delix approach does not require drastic change to healthcare infrastructure and would be able to prescribe a Delix drug like SSRI.” Olsen said the non-hallucinogenic compound will be tested in humans within the next year or so and should be in clinics soon after that.
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