By Brad Dunn —
Benjamin Lightburn has built a career on the belief that compounds extracted naturally from plants and fungi are superior to those synthesized in a lab. He and many of his colleagues at the botanical-extraction company Mazza Innovation exited in 2018, only to reunite in 2020 to launch Filament Health, where they shifted from nutritional plant extractions to magic mushrooms.
Today, the Vancouver-based biotech has eight issued patents related to psilocybin and psilocin extraction, as well as an FDA-approved Phase 1 clinical trial underway at the University of California, San Francisco’s Translational Psychedelic Research Program. Lightburn recently fielded questions about the drug trial, the role of consumer sentiment, the vast uncharted areas of psychedelic research, and the critical importance of Oregon’s rollout of legal psilocybin.
Let’s start with natural versus synthetic, in general. With consumable products, people seem to favor those that are naturally sourced. Do you think this sentiment will carry over to psilocybin as it becomes more available?
I do — most people have a preference for natural products. But strangely, the pharmaceutical industry doesn’t see it this way and most psilocybin drug development is currently focused on synthetics. In every other industry, it’s taken as gospel that people want more natural products. If you showed up at SupplySide West, the nutrition industry’s largest trade show, with synthetic caffeine or synthetic green tea catechins, you’d get blacklisted. It’s the same in cannabis, yet the pharmaceutical industry still needs to be convinced.
But many popular prescription drugs are essentially plant-based, correct?
Yes, over 40% of drugs that have ever been approved have a natural or botanical origin. There’s a strange cognitive dissonance — the pharmaceutical industry is completely dependent on natural products, yet there’s an assumption that natural products cannot be pharmaceuticals. It’s very strange. The best-selling cancer drug of all time, Taxol, is a natural product made from yew tree extract.
Where do you think this cognitive dissonance comes from?
As a blanket statement, synthetic manufacturing is much easier. It’s more repeatable, the ingredients are exactly the same every time. It’s like making chairs from plastic — it’s much easier than making them from trees. Over the years, pharma (especially western pharma) has fully embraced synthetic drug development to the exclusion of natural. But we believe the pendulum has swung too far.
Filament has three natural products currently in trial at UC San Francisco — an oral psilocybin, an oral psilocin, and a sublingual psilocin. What primary results are you hoping to see?
Among other things, we’re hoping to see a faster onset time and fewer side effects with psilocin. When you eat a magic mushroom, your body has to break down the psilocybin into psilocin, which is the psychoactive ingredient. This mostly happens in the gut and might be what causes nausea for some people. Then the psilocin enters the bloodstream, crosses the blood-brain barrier, and causes a psychedelic experience. By administering psilocin directly, we hope to alleviate that gastrointestinal activity. And when taken sublingually, you put a tablet under your tongue, it permeates directly into the bloodstream, and goes right to your brain, so you might get the psychedelic effects much more quickly.
One of the other selling points of a natural extract is the possibility of “the entourage effect,” which is believed to occur from the combination of other psychoactive compounds in the mushroom besides psilocybin. How much research has been done on this?
There’s limited clinical research into the entourage effect. I know of one animal study, where they looked at something called marble-burying behavior in rats. They compared a synthetic psilocybin to a natural extract, and they found that the extract had a greater impact. But clinical evidence is limited, for sure. That said, there is a very large amount of anecdotal evidence from people consuming different kinds of mushrooms and reporting different psychedelic effects. Another big asterisk here, of course: people self-reporting their psychedelic experiences must be taken with a big grain of salt. But if it’s true that different mushrooms cause different effects, then it must have something to do with what’s in the mushroom. And a natural extract will contain these components whereas pure synthetic psilocybin will not.
I saw a study somewhere that showed one of those entourage compounds, baeocystin, actually has more psychoactive potency than psilocin?
Yes, they’ve researched some of these specific compounds, but researching isolated baeocystin in different dosages is not the same as researching the entourage effect that comes from the naturally occurring spectrum of compounds present in the mushroom. This is an important point to keep in mind: the entire known set of psychedelic alkaloids have not been studied in combination, nor have most of them been studied in isolation. So, baeocystin or norbaeocystin or norpsilocin, any of the compounds found in magic mushrooms, could yield huge discoveries in the future. We’re most excited about our psilocin-based drug candidate. Nobody’s studied psilocin in a clinical trial before.
Why do you think that is?
Psilocin is very difficult to manufacture synthetically. We figured out how to extract it naturally, but it’s still crazy that we’re the first ones ever to put it into a clinical trial. It gets back to your question about baeocystin, though: there’s no rule that says that psilocybin is the best compound from the magic mushroom. It could turn out that it is indeed baeocystin. We think it could be psilocin, but it could be any number of compounds.
The amount of unknowns in this field is astonishing. Albert Hofmann and his team at Sandoz discovered psilocybin a half-century ago. Considering how rapidly other sciences have advanced since then, you’d think we’d be further along understanding how these compounds work.
There’s still a whole uncharted continent to explore, with more unknowns than knowns. But the idea that synthetic psilocybin is the be-all and end-all simply because it was the thing that Hofmann was able to manufacture in 1958, and we haven’t iterated on it since then, to us is highly questionable.
Yet, most of the R&D money in this field has gone toward synthetic psilocybin. Do you believe you might be sitting on a scientific goldmine by researching natural forms?
That’s what gets me up in the morning! And I think this is the thing that unites our whole company. We believe we have the ability to create products that could potentially help hundreds of millions people, real people with real needs, in ways that just aren’t being explored by other psychedelic drug developers.
When it comes to patents and IP, what are the pros and cons of developing drugs in natural versus synthetic forms?
Well, contrary to popular belief, you can create IP around natural products. You might not be able to patent a naturally occurring compound, but you can patent methods of manufacturing natural things and extracting compounds from them. The difficulty is creating a stable, standardized pharmaceutical-grade form. My team and I are former colleagues from other botanical-extraction companies and although we have significant expertise in this area, getting our products into a stable, standardized form has been one of the most difficult challenges of our careers. But we believe we’re the first to do it — and to patent it.
How do you think natural and synthetic psilocybin will compare cost-wise for the end user?
Neither version has yet been scaled up to a commercial level. That said, we are confident that our product will be priced significantly lower than a synthetic version. This is especially true in a non-medical distribution model where you don’t need a prescription. In a pharmaceutical model all costs rise, because you have expensive clinical trials that the pharma companies have to recoup. You have prescriber costs that are very expensive. You have medical professionals that need to observe the psychedelic experience. Hopefully insurers will help but we need lower-cost options for people who don’t have insurance, and that’s where we believe natural psilocybin has an important role to play.
Oregon will be the first test case of a non-medical distribution model, where psilocybin will be neither prescribed nor approved as a drug, and users will have to sign a disclaimer saying they understand that. As the first legal marketplace for psilocybin in the U.S., what role if any will Filament play?
We believe we have a duty to help the Oregon rollout, because without psilocybin standardization, people won’t know the strength of the doses they take and the effects will be uncertain. Psilocybin products cannot be imported into Oregon or cross state lines but they can use technology that’s been developed elsewhere, and we have technology which creates standardized doses of natural psilocybin. We’re planning to develop partnerships with local manufacturers and to work with the different analytical labs to share our expertise in testing. We want to support the Oregon market because it is a test for rollouts in other jurisdictions and it is in everyone’s interest for it to go well.
What would cause things to go badly in Oregon? Untested mushrooms that cause bad experiences? What’s the worst-case scenario?
Psilocybin is very safe. But the worst-case scenario is that somebody has a bad experience and maybe even a death attributed (rightly or wrongly) to the experience t, causing negative public perception around psilocybin. Or you could have unscrupulous manufacturers that use adulterants in their products and someone gets seriously hurt.
We all have a responsibility to make sure that Oregon goes as smoothly as possible – it will be a playbook for future markets if it goes well. Most importantly, the potential for healing on a global scale could begin there — millions of people around the world could benefit from treatment with natural psychedelics and we hope that Oregon will be an important step towards our goal of helping them.