Botanical Therapeutics For CNS Disorders

A conversation with Joel Stanley, founder and CEO of AJNA Biosciences

As interest in plant-derived medicines continues to grow among both physicians and patients, some researchers are returning to nature to develop botanical therapies — including cannabis and psychedelics. These contain compounds that have a profound impact on the central nervous system.

In this Q&A, Life Science Connect's Morgan Kohler caught up with Joel Stanley, founder and CEO of AJNA Biosciences, to talk about botanical drug development.

AJNA appears to embrace the potential synergy of whole plant or multi-compound formulations. How does this change your approach to mechanism of action studies and preclinical pharmacology?

From a preclinical pharmacology perspective, the fundamental goal doesn’t change —  developers still need to establish a sufficient understanding of safety, pharmacology, and biological activity before and during clinical development. What often differs in botanical drug development is the starting point. Many botanical drug candidates begin with extensive histories of human use and substantial existing scientific literature, which can meaningfully inform development plans and, in many cases, reduce the amount of new nonclinical work required compared to a new chemical entity.

When additional nonclinical studies are required, we're evaluating the botanical drug substance itself rather than a single isolated active ingredient. That means the focus remains on the same core areas, such as toxicology, genotoxicity, reproductive toxicology, and other standard assessments, but the studies are performed on the full botanical drug substance rather than an isolated API.

That prior knowledge can significantly reduce development risk, shorten timelines, and accelerate the path into clinical trials compared to a new chemical entity. While important nonclinical requirements still need to be addressed, botanical drug developers are often building upon decades, centuries, or even millennia of accumulated human experience and scientific evidence rather than starting from square one. That's a meaningful advantage in an industry where many programs consume years of development and significant capital before reaching a human trial — and many never reach the clinic at all.

The same principle applies to mechanism of action studies. For example, with our tryptamine-based programs, we can run serotonin receptor binding studies similar to those used for synthetic psilocybin or psilocin-based drugs. We identify and evaluate the active compounds, but the FDA’s botanical drug framework allows developers to evaluate the botanical drug substance as a complex mixture, rather than reducing it only to a single active molecule.

While a complete mechanism of action is not always fully understood at the time of approval, developers still need to build a scientifically credible understanding of the drug’s activity. The goal is to explain as much as can reasonably be understood and continue building that understanding through additional studies. In practice, the scientific and regulatory principles are very similar to conventional drug development; we're simply applying them to a botanical drug substance rather than a single active ingredient.

How do you think botanical drug developers can build durable intellectual property (IP) strategies while still working with naturally derived compounds?

Botanical drug developers can build durable IP strategies through proprietary science, patent protection around the underlying plant and manufacturing process, and the inherent complexity of producing a consistent botanical drug.

Our lead candidate, AJA001, is protected through intellectual property covering its proprietary genetics and unique phytochemical profile. As a founder of Charlotte’s Web, I was one of the inventors of the genetic variety used for AJA001, and that ultimately received the first-ever plant variety patent for cannabis. You can patent your base material, and we've been doing it for a long time. Beyond the genetics themselves, botanical drug developers can further strengthen their IP position through utility patents, process and manufacturing patents, formulation innovations, and carefully protected trade secrets.

Beyond that, botanical drugs benefit from a natural moat that extends beyond traditional intellectual property protections. Once you have a complex multi-compound botanical drug, it's extremely difficult to genericize and, in many cases, may be practically impossible to reproduce as an identical pharmaceutical product. Unlike a single-molecule drug, which can be readily replicated once patent protection expires, botanical drugs are much harder to copy identically, particularly at the scale, consistency, and characterization standards required by the FDA for generic drug development.

That's a sharp contrast to many conventional drugs, where sales can drop significantly once generics enter the market. With botanicals, that generic revenue cliff doesn't really exist. If a botanical drug works, its greatest long-term threat isn’t an identical copy — it’s a better therapy. This shifts the competitive landscape from one of replication to one of improvement, and that’s exactly how innovation should work.

What translational models or preclinical assay systems have been most valuable in helping AJNA evaluate safety and efficacy of complex botanical formulations?

One of the major advantages of botanical drug development is that we're often working with compounds that already have extensive histories of human use. In the case of our lead programs, there is a long history of human use and a substantial body of modern scientific literature providing insight into safety, tolerability, biological activity, and potential mechanisms.

That gives us a significant head start compared to a new chemical entity. While we still conduct the studies required to support development, we can also draw from an unusually large body of existing human safety data. In many cases, there is far more real-world safety information available than would ever exist for a novel synthetic compound at a similar stage of development.

Characterizing complex botanical formulations presents its own challenges, particularly when dealing with thousands of molecules. But when it comes to understanding safety, the depth of historical and contemporary human data available for these botanicals is one of our most valuable tools.

As computational biology and AI become more integrated into early drug discovery, where do you see the greatest opportunity for these tools to accelerate botanical-based therapeutic discovery?

The greatest opportunity is in helping us process and interpret massive amounts of data more efficiently. As we characterize botanical compounds, we're often analyzing extensive mass spectrometry and nuclear magnetic resonance (NMR) data sets to identify and understand molecules that have never been fully characterized before. Tasks that previously could take highly trained analytical chemists weeks or even months can now be completed in a fraction of the time using machine learning, advanced computational chemistry, and high-performance computing tools.

These technologies are also incredibly valuable for literature review and meta-analysis. Botanical medicines often have decades, or even centuries, of accumulated research, safety information, and observational data associated with them. Computational tools can rapidly synthesize that information, helping us identify patterns, evaluate evidence, and prioritize development decisions much more efficiently.

Where botanical drug development differs from many new chemical entity programs is that we often begin with substantial existing knowledge of a compound's safety profile, biological activity, and historical use. AI and advanced computational methods help us organize and leverage that knowledge faster, allowing us to move more efficiently through the discovery and development process. Nature has spent millions of years refining these complex chemical relationships. Rather than stripping them down to a single compound whenever possible, our goal is to understand how these naturally occurring groups of molecules work together within biological systems. AI, computational biology, and advanced analytical tools are giving us unprecedented ability to characterize that complexity and translate it into reproducible therapeutic outcomes for patients.

What formulation and clinical design challenges has AJNA had to overcome with its autism candidate AJA001?

Autism is an incredibly broad spectrum, which creates significant challenges both in formulation and clinical trial design. Unlike conditions caused by a single gene mutation or deficiency, autism involves a complex mix of genetic, environmental, and developmental factors, and we still know relatively little about why one person receives a diagnosis versus another.

That complexity is why current FDA-approved therapies, as well as our AJA001 program, focus on a specific and measurable target: irritability associated with autism rather than attempting to treat autism itself. From a clinical design perspective, one of the key challenges is defining clear endpoints and selecting validated measures that can reliably capture improvements in symptoms, such as irritability, anxiety, aggression, or self-injurious behavior.

From a formulation perspective, AJA001 takes a different approach than conventional pharmaceuticals. Rather than targeting a single receptor or neurological pathway, we're studying a multi-compound, plant-derived therapy that may influence multiple neurological pathways and other interconnected biological systems while reducing irritability associated with autism. Drug development still requires a precise target and measurable endpoint, and for AJA001 that remains irritability associated with autism. At the same time, the body rarely operates in isolated compartments. When one system moves toward balance, the positive effects can sometimes ripple outward in ways that reach beyond the original target of treatment. Developing and evaluating a complex botanical therapy therefore requires not only demonstrating consistent quality and reproducible effects but also understanding how those effects manifest across a diverse autism population.

The encouraging part is that, while autism itself is complex, we do have validated clinical metrics that allow us to observe meaningful outcomes in patients: whether a therapy is reducing anxiety, aggression, or irritability and improving day-to-day functioning.

About The Expert

Joel Stanley, former CEO and chairman of Charlotte’s Web and now a board member of DeFloria, leads AJNA BioSciences in developing next-generation botanical therapeutics. At AJNA, his vision is to expand access to pharmaceutical-grade botanical psychedelics designed to address mental health and neurological disorders. By building an ecosystem of natural wellness solutions, AJNA is unlocking the full potential of botanical compounds through sustainable, FDA-approved formulations that redefine plant-based medicine.