Magic Yeast Is Another Way to Produce Psilocybin

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In 1976, the McKenna brothers wrote Psilocybin: Magic Mushroom Grower's Guide under their pseudonyms O.T. Oss and O.N. Oeric — the first ever book on growing magic mushrooms at home. What’s less commonly known is that around the same time, writer and psychedelic enthusiast Adam Gottlieb wrote The Psilocybin Producers Guide, a book focused entirely on getting psilocybin without the relative hassle of growing mushrooms from start to finish. The key to the book’s claim was that by growing mycelium in liquid culture, and harvesting at just the right time, you would get a decent dose comparable to what you might expect from the mushrooms themselves. So, is there anything to these claims, and why did Gottlieb’s work not get more attention?

In his 1976 book, which was reissued in 1997, Gottlieb claimed that 100 grams of dried mycelium produced using his liquid culture method would optimally contain about half a gram of psilocybin, a potency equivalent to a relatively weak strain of Psilocybe cubensis. Although not cited directly, a 1964 study by Philip Catalfomo and Varro Eugene Tyler was likely an inspiration for Gottlieb’s methods. Through careful manipulation of growth parameters, the researchers managed to optimize their Psilocybe cubensis liquid culture to produce about 1% psilocybin after 7 days, in 110 dry mg of mycelium. Interestingly, Psilocybe cyanescens and Psilocybe pelliculosa were also tested, but neither produced psilocybin in the culture medium used.

A year later, in 1965, researchers using a slightly modified version of Catalfomo and Tyler’s recipe found that psilocybin could also be obtained from liquid cultures of Psilocybe baeocystis mycelium. This research, and other studies of Psilocybe cubensis in the mid-1970s, found that the liquid culture recipe was a key factor in whether the mycelium produced psilocybin, with some recipes resulting in no production at all. Most studies also found that psilocybin production peaked early on, at around 5-7 days, then became less concentrated as the mycelium reached its maximum growth at around day 9-11.

Factors such as precise liquid culture recipes and variable production outcomes might have been some of the reasons that early psychedelic enthusiasts had mixed success with Gottlieb’s methods. Compared to growing easy-to-observe mushrooms, knowing when wispy little strands of wet mycelium are prime for harvesting is a harder target to hit. Fast forward to today, and those looking to get the magic without the mushrooms at home might have a few other options — provided they can obtain genetically engineered strains of microbes, or tricky-to-purchase chemical precursors.

In 2017, researchers in Germany learned precisely how Psilocybe cubensis produces psilocybin, paving the way for genetic modification of other microorganisms to optimize production. Since then, a flurry of bioengineers have inserted the newly discovered genes for psilocybin production into other microbes, such as bacteria, molds, and even brewer’s yeast. The first of these experiments began with the fungus Aspergillus nidulans in 2018, yielding 110 mg/L of psilocybin. Compared to the original research done with Psilocybe cubensis in the 1960s, this equates roughly to a threefold improvement on production. Only a year later, another group of researchers jumped the shark by putting the same genes into the bacteria E. coli, and squeezed it to produce an impressive 1.16 g/L — nearly 33 times more than Psilocybe cubensis mycelium has been recorded to produce.

Another option is to use genetically modified yeast, as researchers in Denmark did back in 2020. Using a modified strain of the yeast Saccharomyces cerevisiae, typically used in baking and brewing beer, the researchers obtained an average of 627 mg/L psilocybin and 580 mg/L psilocin. Though not as impressive as the E. coli results, this study used a method called de novo synthesis (from the Latin for “from the new”), meaning psilocybin could be made from simple sugars and other readily available chemicals. Both bacterial and fully synthetic methods of psilocybin production rely on 4-hydroxyindole as a key ingredient, which may be hard for those without a lab to obtain, as most chemical supply companies won’t deliver to a residential address.

To get a better sense of the feasibility of home-biotech psilocybin production, we spoke with Dr. Nicholas Robertson, a bioengineer at the University of California, Riverside, who recently made a video discussing the 2020 yeast paper in more detail.

So let’s all go and get some strains of genetically modified microbes and start brewing psychedelic hooch in our basements, right? If these microbes didn’t contain psilocybin at the point of sale, they would probably be legal to buy and sell, much like mushroom spores in most countries. However, given their ability to produce illegal drugs, you’re unlikely to find a lab willing to supply you with them at present. Assuming you could easily obtain any of the genetically modified strains, though, Dr. Robertson thinks yeast would be the easiest to work with in a home setup:

Despite the Danish research using a modified version of brewer’s yeast, Dr Robertson says not to expect to get drunk as you get high:

However, as any avid homebrew beer maker will tell you, avoiding contamination isn’t easy. Dr. Robertson thinks that brewing psilocybin with these microbes is even harder:

Similarly, in liquid cultures of mycelium, unless there’s an obvious foul stench or weird discoloration, the mycelium of contaminants like Trichoderma are hard to tell apart from those of Psilocybe cubensis or other psychedelic fungal species. For this reason, some mushroom growers avoid liquid culture entirely, as they feel the risk of spreading contamination deep into their grow projects is too great. If you’re recommending that people chug this potentially contaminated liquid, it’s easy to imagine even more people would be turned off. Dr. Robertson urges caution here, too:

The term “crude” is used in the chemical sense, meaning “non-selective.” If you’ve ever drunk mushroom tea or made a psilocybin tincture (cheeky plug for our books here and here), you’ll know that there’s nothing wrong with a crude extraction, but only if your starting material is pure.

To give Gottlieb his due, his book does walk folks through extracting psilocybin from liquid-culture mycelium. However, the use of the chemicals detailed in Gottlieb’s book could just as easily pull mycotoxins from contaminated cultures as well as psilocybin from pure ones. In addition, “downstream chemical extraction of cultures has room for toxic error,” according to Dr. Robertson.

Despite the risks, with enough money, access to a lab, and enough microbiological know-how, it is possible to get high on psilocybin without growing a single shroom. In 2020 Mimosa Therapeutics, a now-out-of-business public benefit company started by Beckley Foundation’s Amanda Fielding and psychotherapist James Keim, were one of the first companies to build their business model around psilocybin produced in large-scale mycelium bioreactors — think liquid culture, but at the size of a brewery. The company went on to produce “mycelium pearls” using its bioreactor methods, which were released in limited quantities in the Netherlands. Though Mimosa Therapeutics went out of business, forward-looking regulations such as those currently being drafted in Oregon allow room for psilocybin from both mushrooms and mycelium, while explicitly blocking the synthetic versions offered by COMPASS and the like.

Other companies are going down the genetically modified route, some choosing to include psilocybin and other psychedelics as part of a wider chemical portfolio—including dyes, skin care ingredients and health supplements. Housing the risky business of psilocybin production within a larger chemical manufacturing company, in the current market where supply is much higher than legal demand, might protect these businesses from betting the farm and running out of capital, as many in the last few years have.

We’d love someone to send us a strain of magic yeast, so we could dust off our old homebrew kit and start running bootleg bottles of psilocybin hooch — although we’re not sure if we’d trust ourselves not to get sick. We’ll probably stick with the mushrooms — but if you’re up for a challenge, it might be time to befriend some Danish biotech folks.

This post is a syndication from “A Quickly Changing Kaleidoscope,” written by Dr. K. Mandrake and Virginia Haze, the authors of the critically acclaimed The Psilocybin Mushroom Bible and The Psilocybin Chef Cookbook.

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