Why Numinus is developing psilocybin tea for research

Numinus Wellness (TSE:NUMI) has developed a psilocybin-containing tea bag for clinical research and potentially for clients in psychedelic-assisted therapy.

The Vancouver–based company’s strategy differs from that of other companies that have popped up in recent years with the intent of creating bespoke psychedelic compounds with patent protection. Some companies, for instance, have created deuterated psilocybin analogs with a shortened half-life. Others have synthesized patentable compounds inspired by other classic psychedelics such as DMT or LSD.

Conversely, Numinus and its rival Compass Pathways (Nasdaq:CMPS) intend to provide psilocybin-assisted therapy. While Numinus is using validated strains of Psilocybe cubensis in a tea, Compass Pathways is exploring a synthetic, high-purity polymorphic formulation of psilocybin.

Numinus was the first publicly-traded company to win a license from Health Canada related to psilocybin.

Numinus plans on studying its tea in a Phase 1 study of mental health professionals receiving experiential training for psilocybin-assisted therapy. The company ultimately aims to use the tea in more research. It is planning trial partnerships at Cedar Clinical Research, Numinus’ clinical trial management division.

The company has also submitted the product to Health Canada for inclusion on the psilocybin supplier list for Canada’s federal Special Access Program.

To learn more about the company’s plans to develop a psilocybin tea and how it distinguishes itself in the psychedelic space, we recently spoke with Sharan Sidhu, vice president of scientific research, innovation and laboratory operations at Numinus.

What is the backstory of your efforts to develop a psilocybin-based tea?

Sidhu: We are a Health Canada–licensed facility. We have multiple substances licensed, including a number of different compounds such as psilocybin, psilocin, as well as psilocybe mushrooms. We also have a couple of other species on our license, but it is the psilocybe that we are most focused on at the time.

There are a lot of unknowns in discovery work involving the metabolites or compounds in mushrooms. We’re developing a database.

The goal is to formulate these products into something the regulators can accept. We work in the interface of natural products for pharmaceutical purposes. So it’s a very difficult area to be in. It requires more validation and regulatory compliance than an active pharmaceutical ingredient (API) product. With an API, you have a single matrix effect. With a mushroom-derived product, you have a complex matrix, so you have complex effects.

We are cultivating validated strains of mushrooms. We were one of the first licensed facilities in North America. And we’re developing genomically validated strains aligned with their metabolome — the compounds they produce and the phenotype.

When making drug products using natural materials as starting materials, the regulators want to see how we’re limiting variability to make our product more acceptable as a botanical drug or a fungal drug.

To help limit variability, our mycologist uses sector isolating, which involves isolating sectors in a Petri dish. Then, we’ll take this through a validation process and grow it several times to ensure that the genome and metabolome are aligned. After that, somebody else in our group does the principal component analysis.

We ensure that the compounds’ metabolites — including the alkaloids, of which psilocybin is one — are stably produced at a certain amount. We create this fingerprint and ensure that these metabolites’ fingerprints are stable with that genome for several generations. That is how we produce our validation strains. And genomes for psilocybe cubensis aren’t as well defined as some other species. At the moment, we are just looking at that stable production of the metabolites with the isolates we’re producing.

What can you say about the role of other compounds besides psilocybin and psilocin in the tea?

Sidhu: There are so many compounds in psilocybe cubensis. There hasn’t been a study comparing a synthetic psilocybin compound in one delivery format with a psilocybin mushroom in another. There are a couple of reasons for that. First, it’s pretty expensive to do clinical trials. You have to develop the product. You have to complete all the regulatory requirements for product development. Then, you have to put that product into clinical trials, starting with a Phase 1 study. And then you’d have to do the same thing with a natural product.

We’ve gotten to that point where we have an actual product in a tea format that is as close as we can get to the actual mushroom itself. Now, we’re probably better positioned to do a study like that. We have a natural product that’s stably reproducible.

The minute you take a mushroom compound and process it, stabilizing that long-term is where we start getting issues. And if it’s not stable for an extended period of time, then it’s not very commercially viable.

Now that we have the tea product, we can start looking at how it compares to synthetic psilocybin. We’re starting by looking at a comparator in a cell line model rather than first going out and doing a study comparing psilocybin and a complex psilocybin product. We will first look at the differences we see in a cell line model because that’s a far cheaper way of doing it than taking it into a human trial.

We have a couple of theories of how psilocybin tea will compare to synthetic psilocybin.

Psilocybin is converted in the body to psilocin, which binds to serotonin receptors. Other compounds in the mushroom modulate the effect of that bonding. All these other compounds can modulate the bonding of psilocin. We know that initial animal studies show a better effect of a mushroom product than the actual psilocybin compound itself.

Think about the comparative percentage of indole alkaloids to all of these other compounds in the mushrooms. These haven’t been studied for such a long time. We don’t know what we’re missing. We are regularly identifying compounds. Just yesterday, my chemistry tech said she wanted to add another 25 compounds to our database. Many of those compounds can contribute to cognition, general health and wellness. There are so many functional molecules in these mushrooms that are in a higher amount than psilocybin and, consequently, psilocin. So our concept of synergism within these mushrooms is beyond just the synergistic effect we have at the 5-HT receptor site.

Can you share more on your focus to develop a psilocybin-based tea?

Sidhu: I just had a meeting with AHPA, the American Herbal Products Association. I am part of the AHPA Psychedelic Plants & Fungi Committee. They are part of this discussion about natural products, and why would you change something that’s been working for millennia? What can we learn from what was done historically and push that forward instead of reinventing the wheel?

Some therapists believe the psychedelic effect is an essential component of the therapy. Changing the way the binding takes place at the 5-HT receptor could potentially change how the psychedelic effects manifest. If we look at it from a genomic and a transcription factor perspective, when psilocin binds to a 5-HT receptor, there’s a knock-on effect. You get this transcriptional regulation that is very specific to psilocin and LSD. The transcriptions affect the frontal cortex of the brain. But you only see that when psilocin binds to that 5-HT receptor. You don’t see it when serotonin binds it. It’s very specific and linked to the upregulation of activity in the frontal cortex. I believe that that’s a really important part of that psychedelic effect. So if you take that out of it, then is it still a psychedelic? And is it still going to have the same effect?

And can you talk more about the tea itself?

Sidhu: The tea is from psilocybe cubensis. We have a strain we developed called BP-STAR that has been validated in-house. We know what its genome and metabolites are and that it’s stably reproducible. Reproducibility is a key component in getting the regulators to accept a product. Secondly, there are components like experimental procedures that we went through to get to the perfect optimized delivery of the tea. So those are the components we put in there, how we did the experimentation, specific temperatures, specific brew times. It’s a very simple product, but it’s very effective. The work that we’ve done on the validation and optimization of how we produce the tea is what’s unique about it.

For us to submit this product to Health Canada, we have to show them validated results of how we prepare this material, how we get it into a delivery system, and how it will be stably reproducible when we get it to the patient. So although there are lots of anecdotal stories about how to use psilocybin, we still have to reproduce all that data in-house time and time again over several batches to have a statistically significant result that we can submit to Health Canada and the FDA.

So you have a Phase 1 study planned?

Sidhu: Yes, a Phase 1 study is planned at our Vancouver clinic.

The Phase 1 study should be quite a simple turnaround, and then we can look at where else we want to put this product.

Numinus is active in several areas, ranging from clinical trials to counseling. How does that fact influence your work?

Sidhu: It makes it an interesting piece of work because there’s never a dull moment. There is also just learning from each other. I’m not going to have the therapeutic expertise and input that someone like Joe Flanders, our vice president of psychology. I also learn a lot from Dr. Evan Wood, our chief medical officer. Joe and Evan have expertise in areas that I don’t. So when I think about how we’re developing a product, I talk to them. There’s no point in developing products for unrealistic use. And from a clinical and client perspective, we want to develop affordable products. So we have a holistic view. We are considering not just the product development aspects but what paradigms investigational products could be used in. We are considering what kind of clinical model they would be using. And then you’re looking at the therapists’ perspective as well. How do they want to deliver this product? Something like the tea would be great for a group therapy session. A calming group therapeutic product may not be realistic for someone with major depressive disorder or something like that.

We’re looking at it from more than one point of view. When developing a product, we consider where it is going and its best use.

Some companies are developing products that have taken the psychedelic out of the psychedelic product. So I ask my therapists in the team, ‘Hey, do you think this is a good idea? Is the psychedelic aspect important to therapy?’ So, that dynamic within our group benefits us from a drug development perspective.

Do you think the growing interest in psychedelics could result in backlash?

Sidhu: Absolutely. That’s a concern of mine. All of a sudden, we have a number of dispensaries popping up. There has been an uptick in use. We see reports of people claiming psychedelics cured them of several different conditions. However, it will just take a couple of incidents to set us back. And we’ve come so far.

We don’t want to be in another kava situation. Kava saw a surge in popularity, and then there was this negative pharmacotoxicity study, and we saw worldwide removal of kava products from the market globally. Before that, kava was being studied against benzodiazepines. We don’t want to get into that situation where we see this global removal of an effective product because it’s not been used, grown or tested properly. That’s where we could see a setback. I get concerned when I see new dispensaries with people giving medical advice who shouldn’t be. It’s a big concern because we don’t want to be set back.