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 brain 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 potential 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, and 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 not just for 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 Inhibitor (SSRI), 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 treatments, which 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, which could potentially 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 big Pharma companies about potential partnerships and licensing opportunities, and Olsen said big Pharma is interested in this space and everyone is trying to figure out what the best bet would be going forward.
“We are unique 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.
In The News
LOS ANGELES — Winners have been announced in the $5 million carbon removal student competition award program launched by XPRIZE... Read More
LOS ANGELES — Winners have been announced in the $5 million carbon removal student competition award program launched by XPRIZE with support from the Musk Foundation, to fund early-stage concepts and remove barriers of entry for carbon emission removal innovations. Teams led by enrolled student competitors... Read More
This article is by Prachi Patel and was originally published by Anthropocene magazine. Wood seems to be the gift that keeps on giving.... Read More
This article is by Prachi Patel and was originally published by Anthropocene magazine. Wood seems to be the gift that keeps on giving. Researchers have tinkered with its chemistry and physical structure to make it transparent, squishy, strong as steel, filter water, and turned it into bioplastic and Styrofoam-like... Read More
WASHINGTON — Senate Majority Leader Chuck Schumer, D-N.Y., announced Tuesday that Democrats have reached a deal on legislation to lower... Read More
WASHINGTON — Senate Majority Leader Chuck Schumer, D-N.Y., announced Tuesday that Democrats have reached a deal on legislation to lower prescription drug prices. "It's not everything we all wanted. Many of us would have wanted to go much further, but it's a big step in helping... Read More
Scientists temporarily attached a pig's kidney to a human body and watched it begin to work, a small step in... Read More
Scientists temporarily attached a pig's kidney to a human body and watched it begin to work, a small step in the decades-long quest to one day use animal organs for life-saving transplants. Pigs have been the most recent research focus to address the organ shortage, but... Read More
WASHINGTON -- The foundations of what could prove to be the next great innovations in climate change prevention technology were... Read More
WASHINGTON -- The foundations of what could prove to be the next great innovations in climate change prevention technology were laid out and dissected during a Brookings Institution webinar this week. Sanjay Patnaik, director of Brookings Center on Regulation and Markets, hosted a virtual discussion on... Read More
WASHINGTON — New data presented by researchers from Editas Medicine, a leading genome editing company, reveals that gene editing treatments... Read More
WASHINGTON — New data presented by researchers from Editas Medicine, a leading genome editing company, reveals that gene editing treatments are not only safe in humans, but may hold promise of treating a rare retinal disease that leads to blindness. “We believe these findings validate the... Read More