Homebrew psilocybin
Though growing magic mushrooms are an easy way to access psilocybin, can other methods improve the process further?
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 you 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 this article we’ll look at the fringe mycology and mainstream science behind homebrew psilocybin—the alchemical art of producing psilocybin at home, without ever growing a single magic mushroom.
In his 1976 book, which was released in a second edition in 1997, Gottlieb claimed that 100 g of dried mycelium produced using his liquid culture method would optimally contain about half a gram of psilocybin—a potency equating to a relatively weak strain of Psilocybe cubensis. Though not cited directly, a study by Philip Catalfomo and Varro Eugene Tyler in 1964 was a likely inspiration to Gottlieb’s methods. Through careful manipulation of growth parameters, the researchers managed to optimise 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 be also be obtained from liquid cultures of Psilocybe baeocystis mycelium. This research, and other studies of Psilocybe cubensis in the mid-1970s, found that 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 optimise 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 started with the fungus Aspergillus nidulans in 2018, resulting in 110 mg/l psilocybin produced. Compared to the original research done in with Psilocybe cubensis in the 1960s, this equates roughly to a three-fold 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 out of Denmark did in 2020. Using a modified strain of the yeast Saccharomyces cerevisiae, typically used in baking and beer making, the researchers were able to get 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“), which meant that psilocybin could be made from simple sugars and other easy to obtain 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 purchase, as most chemical supply companies won’t deliver to a residential address.
To get a better idea of the feasibility of home-biotech psilocybin production, we spoke to Dr Nicholas Robertson, a bioengineer at the University of California, Riverside who recently made a video looking at 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? It 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 set up:
“The advantage of yeast would be that they're more familiar to the average home brewer and have already been engineered to produce psilocybin from glucose (albeit in much lower quantities), with no hard to access precursors.”
Despite the Danish research using a modified version of brewer’s yeast, Dr Robertson says to not expect to get drunk as you get high:
“You’ll probably end up with around 2% alcohol. The yeast we commonly use for brewing have been selected for alcohol production, whereas strains used to make bread yeast don’t produce much alcohol.”
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:
“Without experience culturing microbes, someone may accidentally grow a microorganism that isn't what they intend, and this could make you very sick. Growing these microbes in a sterile condition would probably be around five times harder than your average batch of homebrew beer or kombucha.”
Similarly in liquid cultures of mycelium, unless there’s an obvious foul stench or weird discolouration, 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 then recommending people to then chug this potentially-contaminated liquid, it’s easy to imagine even greater numbers would be turned off. Dr Robertson urges caution here too:
“Drinking several milliliters of any microorganism is not recommended. Even in brewing alcohol, the yeast is typically allowed to settle to the bottom before bottling. Commercially, the product is also pasteurized. If you don't do this, it will give you stomach issues. So the best practice would be to do at least a crude extraction on your broth.”
The term “crude” here is a term we use in the chemistry 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 credit, his book does walk folks through extracting the 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 their bioreactor methods, that saw limited release in the Netherlands. Though Mimosa Therapeutics went out of business, forward-looking regulations such as those currently being drafted in Oregon allows 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—though 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.
Adam Gottlieb was a pseudonym for John Mann..
Terrence & Dennis McKenna were NOT the ones who germinated the idea to create the 1976 Magic Mushroom Growers Guide..that person was Obscure,…Irimias the Obscure.