Psilera: No Trip Approach To Mental Health & Dementia

“We consider ourselves a biotech company primarily focused on therapeutics. While we started in a space associated with psychedelic molecules, our compounds are non-psychedelic. Our identity is rooted in being a biotech company exploring innovative solutions for various conditions, including mental health, neurodegeneration, and addiction.”

-Chris Witowski, PhD, CEO of Psilera

Psilera was founded in 2019 by two PhD natural products chemists with a focus on identifying and designing molecules, influenced by those found in the natural world, for treating neurological conditions.

While Psilera frequently references the inspiration they find in nature, they aren’t content to simply work with what our Earth provides. Instead, they seek to enhance molecules through a proprietary screening platform which identifies opportunities for improvement – such as making slight tweaks to the molecule so that it binds better to a receptor, or to a different receptor to reduce side effects.

This process led to the development of PSIL-006, Psilera’s lead clinical compound.

“Getting you there without the trip”. That’s a hell of an intro.

 

About PSIL-006

“PSIL-006 exhibits a novel mechanism of action, distinct from both existing therapeutics and first-generation psychedelics.” – Chris Witowski, PhD, CEO of Psilera

PSIL-006 is Psilera’s lead clinical candidate. It’s a non-hallucinogenic serotonin-6 receptor  (5-HT₆) and 2A (5-HT2_A) dual agonist.

There are several different serotonin receptors. Targeting 5-HT2_A is considered an essential action of classic psychedelic drugs. But targeting this receptor is also linked to hallucinations.

5-HT₆ is among the most recently discovered serotonin receptors. From a drug development standpoint, it’s an attractive target because it’s the only serotonin receptor found exclusively in the central nervous system (CNS). And, 5-HT6 is associated with learning and memory – making it an attractive target for treating cognitive problems.

According to Dr. Witowski, researchers at Psilera are developing PSIL-006 to avoid hallucinations by staying “below a certain receptor occupancy” for 5-HT2_A – in other words, structuring the molecule in a manner that PSIL-006 still targets 5-HT2_A, but not to the full extent possible.

In a previous article, we compared psilocybin with selective serotonin reuptake inhibitors (SSRIs). SSRIs can affect serotonin in areas beyond the brain. And based on an animal study, SSRI treatment failure may be the result of overexpression of a certain serotonin receptor in the brain, leading to a negative feedback loop and a decrease in serotonin levels.

Think of PSIL-006 as psilocybin without hallucinogenic properties. If it’seffective for treating depression, PTSD, neurodegeneration, or other conditions, PSIL-006 could be taken at home without need for supervision. This could greatly scale the number of people who could receive treatment. According to Dr. Witowski, “Pairing it (PSIL-006) with therapy may indeed prove more beneficial, but we’re exploring the potential of dosing PSIL-006 as a drug independently”. The lack of hallucinating properties also opens the door for pairing PSIL-006 with virtual therapy. This would greatly increase the number of patients who could access treatment.

 

Trials

In terms of the drug development process, PSIL-006 is still in very early stages. As in, the preclinical in vivo studies stage.

If your Latin is rusty (I can’t imagine why that would be the case!), in vivo translates to “within the living”.

Preclinical in vivo studies are conducted to determine whether a drug development compound candidate has the potential for causing severe side effects and harm. They also develop detailed information about dosing and potential to treat certain diseases.

Preclinical in vivo studies showed potential for PSIL-006 to cause rapid, positive behavioral change that shows potential for treating conditions within the realms of mental health, neurodegeneration, and addiction.

Dr. Witowski, shed light on one such neurodegenerative disease that PSIL-006 could target: behavioral variant frontotemporal dementia (bvFTD). (We recently discussed the potential for psychedelics and adjacent compounds to treat dementia.)

Neurodegenerative patients can have cognitive issues which hinder the psychedelic guidelines of “set and setting” or preparation and integration. Furthermore, these patients are also at higher risk of psychosis which could manifest with a traditional psychedelic. That’s why a non-hallucinogenic molecule, such as PSIL-006, is an attractive candidate for neurodegenerative disorders.

“BvFTD is a rare, early-onset dementia impacting the frontal lobes and prefrontal cortex. PSIL-006 seeks to provide a rapid behavioral benefit for patients lacking approved treatments. Additionally, we believe PSIL-006 could slow or reverse the disease’s pathology, ultimately improving patients’ quality and length of life.”

 

Next Steps

“The response has been positive and intriguing. Focusing on neurodegeneration, especially in a rare disease category, is appealing. We are positioned as the first company to explore next-generation psychedelics for neurodegenerative conditions, setting us apart and generating interest in a landscape gaining attention beyond traditional psychiatry.”

– Chris Witowski, PhD

So, what’s coming next from Psilera?

Dr. Witowski informed us that Psilera aims to begin Phase 1 trials for PSIL-006 by early 2025. They also have other promising drug candidates in their pipeline  along with the technology to continue discovering and developing new molecules for underserved patient populations.

Psilera has a patent portfolio consisting of millions of patented next-generation psychedelics. In general, these new drug classes have psychedelic properties in that they work quickly with single doses but are differentiated due to lack of hallucinogenic effects.

 

Conclusion

Several companies are researching the potential of psychedelics without hallucinogenic properties, with their own unique approaches (e.g: selectivity, agonist/antagonist combo). It is an exciting endeavor for both psychedelics and medicine in general.

There are camps within the ecosystem of psychedelics medicine that believe hallucinogenic properties are essential to gain positive benefit therapeutics. Luckily, there is a lot of research being conducted that will clarify and provide more concrete evidence.

As clinicians, we see the economics of psychedelic assisted therapy, required clinician resources for facilitation, patient burden, and exclusions for high risk patients as a reason for the need for non-hallucinogen molecules as a tool for people that won’t be able to access 1st-generation “classic” psychedelics or should not use them due to health reasons – for example, there is concern for cardiovascular toxicity in certain people. Healthcare providers need many tools in their toolbox to provide care for people with different walks in life.

Here is to hoping!