Christopher Pauli is a molecular biologist who co-founded Tryptomics, a Colorado-based biotech that’s developing novel lab-testing technologies and services for plant medicines. One of the company’s focuses is to use pharmacogenomics and microbiomics to create highly personalized, bespoke psychedelic and natural medicines.
Pauli recently shared how his background in Cannabis research led to this work, his viewpoints on current testing standards in psychedelics, and how plant medicines may have a greater impact on gut health than brain health.
What led you to working in psychedelics?
During my degree program at the University of Colorado, I became involved in its Cannabis Genome Research Initiative and that’s how I got into the genetics bioinformatics field. After that I worked for Steep Hill Labs (later acquired by Front Range Biosciences) as a part of their research and development teams, where we focused on developing analytical chemistry methodologies, marker-assisted breeding systems, as well as pathogen testing. We were able to create some really novel chemistry profiles and genetic assays. I was working with Caleb King, and we saw that this technology wasn’t limited to Cannabis. We also used these technologies on other agricultural products like coffee, and when the natural medicine space popped up in Colorado, we saw it as an opportunity to work more in the fungal space and especially with the tryptamine class of compounds, as I was exploring at-home mycology at the time.
Was that the idea behind Tryptomics? How did that come together?
So, we decided to start our own business where our whole vision was to look at different fungi profiles and their tryptamines so that we could develop truly personalized natural medicine. We saw how chemistry and genetics partnered up to do metabolomics. Also, one of our good friends, Ian Bollinger, was starting Hyphae Labs at the time with Reggie Harris. We saw all this exciting stuff happening in the psychedelic and natural medicine space, so that’s what started us down the path of testing tryptamines and other natural products. Thus, we began working with our own HPLC (high-performance liquid chromatography) in Colorado doing tryptamine testing, but also trying to expand that testing to include minor alkaloids and make that the standard for people to see. Because if you get used to seeing 14 tryptamines on your COA (certificate of analysis), it’s really hard to go back and only measuring two even if that’s the only things the regulations require.
You’re talking about things like baeocystin and norbaeocystin and other “entourage” compounds, as they’re called?
Right. These are like the equivalent of cannabinoids — CBD, THC, CBC, etc. — but they’re tryptamines and there are multiple versions of them. Norbaeocystin and baeocystin are precursors to psilocybin, and psilocybin is a precursor to aeruginascin and trimethyltryptamine. They are many tryptamines in mushrooms, and they’re all connected in this biosynthetic pathway.
When did Tryptomics launch?
We officially launched in January 2022. Caleb and I bootstrapped the whole thing and our main revenue at this point is testing services and selling test kits. We also developed a product in Cannabis called ZeroC, which is cannabinoid-free reference matrix that lets labs check the effectiveness of their instruments. This is important because then they can identify common matrix interferences associated with testing when testing for things like pesticides, mycotoxins, heavy metals, terpenes, residual solvents, and microbials.
But our real focus is on the psychedelic and natural product testing side — and with natural plant and fungal medicines, not MDMA or LSD or other synthetics. We’re developing genetic technologies, as well, for marker-assisted breeding programs and pathogen testing that we will license out to other labs. We aspire to be a proof of concept in testing, and to get our technology into all the labs across the country so we get the highest levels of accuracy possible in psychedelics and avoid the pitfalls we see in Cannabis testing.
As far as your testing services, are you seeing more raw mushrooms or mushroom products like chocolate bars?
It’s predominantly fruit, maybe like 70-75%. We do get quite a few chocolate bars and more recently we’ve been working with a couple of different organizations to do some of this screening in different markets. Like, what’s on the shelf in your state? A lot of the chocolate bars being sold right now at bodegas or smoke shops have 4-AcO-DMT. They’re not actually psilocybin products, but they’re labeled as psilocybin products. So we’re doing a lot of work to try and call out what’s happening to protect the consumer.
With Oregon and Colorado leading the way in setting up testing requirements for mushrooms, what safety requirements are being discussed?
Both states have regulated models that are based on health and therapeutic value. But if you’re really concerned about someone’s health, then I think you need to test for more than just psilocybin and psilocin levels. You need to test for heavy metals and pesticides. You likely also need to test for microplastics and PFAS if the goal is to keep people safe and heal them, but that may present cost-barriers to this medicine. Most mushrooms are grown on coconut coir, and every batch of it can be more or less contaminated with metals, pesticides, or microbials. They’re also mostly grown in plastics bags and tubs. I mean, we’re growing a sacred medicine in plastic containers. Can’t we do this in a healthier, more sustainable way? I think this is something that we as an industry would want to figure out right off the bat.
Back to biochemistry and genetics. Is your vision to be able create psychedelics that are highly personalized for individuals’ specific brain chemistry?
Yes definitely. Right now, we first need to know exactly what’s in mushrooms, and so we’re collecting data and variations of these chemical profiles. At the same time, we’re working with Felix Blei in Germany, whose Miraculix lab is studying the entourage effects through an objective survey. Basically, you consume mushrooms that have been fully tested and then compare your experience with others. It’s trying to tease apart individual responses from the various tryptamine profiles. We’re also working with a group that uses an fMRI machine to analyze the same thing. We’ve been pushing ourselves into this pharmacogenomic space to understand how these complex chemical profiles interact with the individual’s receptors and microbiome.
I’m a bio-informaticist, and one of our advisors is a biochemist who did a lot of human genomics work at ArcherDX. So, we’re also exploring how exactly pharmacogenomics can roll out in this space. What does the report look like? We’d like to see a traditional pharmacogenomics report where you send us your 23andMe data on your genome, we analyze it and give you back something that says, “Based on your serotonin receptor profile, you may want to avoid mushrooms that are higher in norbaeocystin, or you may be more sensitive to psilocybin, so you may want to start with a smaller dose to avoid a negative interaction.”
That’s pretty amazing. How far away do you think we are from something like that?
Well, we still have a lot of basic research to do just to understand what other receptors get hit, but there’s a lot of literature out there on this topic. Mushrooms contain more than 400 bioactive compounds, so it’s not just your serotonin receptors, even if those are a huge component. These compounds also hit a lot of other receptors in your body. We will likely see a huge brain-gut interaction, as well. You actually have more serotonin receptors in your gut than you do in your brain. How do these compounds start affecting your gut health and receptors? That’s the third prong of our business: really understanding why psilocybin is useful six months after you use it.
There’s a hypothesis we’ve came up with that it’s probably linked to the antibiotics these mushrooms produce. When you watch cubensis grow, you can see how they overcome bacterial infections, so they are likely producing antibiotics to do so. We don’t necessarily know which antibiotics they are — or what affectivity they have against human microbes — but it’s logical to think that if we eat mushrooms that produce antibiotics then that’s changing our gut health in some way. Everyone has a microbiome profile that we’re just learning through the Human Microbiome Project. And we also know our brain-gut interaction can be linked to depression and anxiety, among many other health conditions.
If we collect and analyze enough biochemical data from humans and natural medicines, we might be able to say, “This mushroom is better for depression because it produces this antibiotic that’ll change your gut health. And just a small amount of it will lead to long-term relief of depression.” This would drastically change the way we look at mental health in America and how these natural medicines are used in the clinics coming at the end of 2024.
