Bench2Bedside:

The first wave of psychedelic medicine has garnered a lot of attention, but we’ve yet to see a meaningful impact for patients. How does your approach differ?

Joseph Tucker, Ph.D., CEO of Enveric Biosciences:

The first wave has largely focused on taking known hallucinogens, such as psilocybin, and translating them into clinical therapies. Many groups have shown meaningful neuropsychiatric effects with these molecules, but they also produce hallucinations. As a result, their treatment models, regulatory strategies, and commercialization plans have had to accommodate supervised, in-clinic administration because the perceptual effects are inherent to the drug.

At Enveric, we are taking a different path. We believe the core therapeutic driver is neuroplasticity, the brain’s ability to repair and reorganize its neural connections. Our strategy has been to design new chemical entities that aim to deliver that plasticity signal while minimizing hallucinogenic effects. Using our Psybrary™ platform, we engineer molecules rather than repurpose naturally occurring psychedelics.

Recent academic research supports this approach. A paper published online in Nature in January 2026 by Xu and colleagues demonstrated that signaling downstream of the 5-HT2A receptor can be separated into pathways associated with antidepressant-like effects and pathways associated with hallucinogenic effects. This work strengthens the scientific basis for developing compounds that seek to preserve therapeutic benefit while reducing perceptual disturbances.

In our own animal models, we have observed plasticity-related effects without behavioral patterns typically associated with hallucinogenic compounds. If those findings translate clinically, this could enable a more scalable outpatient treatment model. In that scenario, patients could potentially be treated in standard clinical settings or at home, rather than in specialized psychedelic clinics that require supervised administration and added infrastructure.

If hallucination-associated therapies are approved, they may still face practical constraints related to access, cost, and clinical logistics. Our objective is to develop therapies that integrate more naturally into existing healthcare systems, with scalability and patient access as central considerations.

B2B:

You’ve spoken about the first-in-class, dual-mechanism behind EB-003. Can you elaborate?

Tucker:

EB-003 is designed to engage two serotonin receptors, 5-HT2A and 5-HT1B. Many programs in this space focus primarily on 5-HT2A because of its link to neuroplasticity. However, 5-HT2A activation is also associated with hallucinations. Our approach has been to engineer EB-003 to engage 5-HT2A in a way intended to drive plasticity while minimizing behavioral effects typically linked to strong psychedelic activation.

Importantly, EB-003 also activates 5-HT1B. A recent paper in Molecular Psychiatry by Fleury and Nautiyal examined 5-HT1B signaling in psilocybin-treated mice. Their findings suggest that when 5-HT1B signaling occurs alongside 5-HT2A activation, the overall behavioral benefits are stronger. When 5-HT1B signaling was blocked, the improvements linked to 5-HT2A were reduced.

We also believe there is value in keeping the pharmacology focused. EB-003 is designed to primarily engage these two receptors, 5-HT2A and 5-HT1B, rather than broadly activating multiple serotonin receptor subtypes. Many 5-HT2A-targeting molecules interact with a wide range of 5-HT receptors, which can introduce polypharmacology-related uncertainty and potentially unwanted effects. By limiting receptor engagement to a defined set, our goal is to achieve a cleaner, more predictable pharmacological profile. A more selective receptor profile can also support clearer dose-response relationships and potentially reduce development risk as programs move into clinical testing.

Taken together, we believe this deliberate dual-receptor design positions EB-003 to drive meaningful plasticity-related changes while maintaining pharmacological discipline and development focus. As the program advances, clinical data will ultimately determine the extent to which these design principles translate into therapeutic benefit. We believe this focused, mechanism-driven strategy represents a differentiated and capital-efficient path to building scalable neuropsychiatric therapies.

B2B:

Where do you see EB-003 fitting into the current treatment landscape for something like PTSD or treatment-resistant depression?

Tucker:

First, I’d like to step back and consider the scale of the mental health challenge around the world. As many as 65 million in the U.S. and 1 billion globally experience a neuropsychiatric disorder at some time in their lives, yet the treatment options that are available have a low efficacy. First line SSRI treatments work for less than half of patients. And when they do work, they take weeks or months to have an impact. Because of this and confounding side effects that cause many patients to stop treatment, few achieve full remission.

So, there’s a lot of room for innovation, and we believe there is a great deal of interest in neuroplastogens, both with and without the hallucination. Recent deals from Otsuka and AbbVie have demonstrated that Big Pharma has an appetite for 5-HT2A candidates, supporting the potential role for these compounds.

EB-003, we think, has the potential to be rapid-acting, while also providing durable benefits. With a safe, non-hallucinatory impact, we envision the convenient and traditional dosing fitting into the standard prescription drug model. We believe a safe, efficacious and accessible profile has the potential to reach millions of people who are suffering and poorly served by current options, and thus these compounds have the potential to take a significant place in the treatment regimen for patients with these very challenging mental health conditions.