mushrooms among test tubes
VICE Magazine

Get Ready for Pharmaceutical-Grade Magic Mushroom Pills

As magic mushrooms make the shift from recreational drug to mental health treatment, patients won’t be eating caps and stems, but a synthetic product made in a lab—one that can be patented and profited from.
Lia Kantrowitz
illustrated by Lia Kantrowitz
28 May 2020, 11:00am

This article originally appeared on VICE US.

This article appears in VICE Magazine's Means of Production issue. Conceived of pre-COVID-19 and constructed during it, it explores the organization and ownership of our world.

In 1955, a bank executive and a New York society photographer found themselves in a thatch-roofed adobe home in a remote village in the Mazateca mountains. Gordon Wasson, then a vice president at J.P. Morgan, had been learning about the use of mushrooms in different cultures, and tracked down a Mazatec healer, or curandera, named María Sabina. Sabina, about 60 at the time, had been taking hallucinogenic mushrooms since she was a young child . She led Wasson and the photographer, Allan Richardson, through a mushroom ceremony called the velada.

“We chewed and swallowed these acrid mushrooms, saw visions, and emerged from the experience awestruck,” Wasson wrote in a Life magazine article, “Seeking the Magic Mushroom.” “We had come from afar to attend a mushroom rite but had expected nothing so staggering as the virtuosity of the performing curanderas and the astonishing effects of the mushrooms.”

Appointing himself as one of the “first white men in recorded history to eat the divine mushrooms,” Wasson inadvertently exposed much of the Western world, and the burgeoning counterculture movement, to psychedelic mushrooms. On the other side of the globe, the Swiss drug company Sandoz received 100 grams of the mushrooms from a botanist who had visited Sabina on one of Wasson’s return trips. They went to the lab of Albert Hofmann, the Swiss chemist who first synthesized LSD. In 1963, Hofmann traveled to Mexico with pills containing synthetic psilocybin, the active compound in magic mushrooms.

“We explained to María Sabina that we had isolated the spirit of the mushrooms and that it was now in these little pills,” Hofmann said during an interview in 1984. “When we left, María Sabina told us that these tablets really contained the spirit of the mushrooms.”

Hofmann’s pills were the first indication that while people can have spiritual and transcendent experiences from eating the mushrooms themselves, they can also have such experiences with a man-made version of just one of the mushroom’s compounds: psilocybin.

This development is particularly relevant today, as scientists study psychedelic mushrooms as potential treatment options for those who suffer from severe depression, addiction, and more. In clinical trials, such as those ongoing at Johns Hopkins University and Imperial College London, participants don’t eat caps or stems. They consume synthetic psilocybin, made in a lab by chemists in a way similar to how Hofmann first made his psilocybin.

It’s a necessary hurdle: Psilocybin mushrooms can be grown relatively easily, and aren’t expensive to produce. But researchers have to source their psilocybin from highly regulated labs because natural products vary, and researchers need consistency in chemical composition and dosage in order to do controlled studies. Clinicians need to know how much of a drug they’re giving to a patient, how long it takes to kick in, and how long it lasts; they also need to be sure their drug isn’t tainted with other chemicals. It also helps to be able to mass-produce large amounts and not be threatened by variables, like weather, that affect agricultural products.

As psilocybin moves closer to becoming a legal medicine meeting all the regulatory requirements, doctors won’t be writing prescriptions for mushroom caps or stems—and this will come at a certain cost. Johns Hopkins researchers have claimed they've paid labs $7,000 to $10,000 per gram of psilocybin, whereas the street price of magic mushrooms is around $10 per gram. Besides the cost of chemical materials, the steep sticker price comes from the labor required to adhere to the U.S. Food and Drug Administration’s strict drug-making standards, known as Current Good Manufacturing Practice.

It’s an unprecedented moment, and psychedelic culture must reckon with what it means for a magic mushroom to become a synthetic pill, to be picked up at your local pharmacy or from a doctor. There’s some wariness in the psychedelic community about what synthetic psilocybin represents: big business, questionable investors, and patents on experiences they think shouldn’t have a price tag or a profit margin. Since it’s a known natural compound, psilocybin itself cannot be patented, but the way it’s made and used can be. Already there are organizations applying for patents for their synthesis process, and innovators coming up with new ways to make large amounts of synthetic psilocybin, all seeking protection for their intellectual property.

From a chemistry standpoint, psilocybin molecules are the same no matter where they come from—plant or lab bench. So the hesitation around big-pharma psychedelics is not about what’s “better” or “worse,” but about the commodification of substances that people consider to be spiritual—and that also could be incredibly helpful medication.

“This is getting into nonscientific questions,” Matt Johnson, a psychologist and the associate director of the Johns Hopkins Center on Psychedelic and Consciousness Research, told VICE. “I think people are reacting to the idea that someone would have the goal to patent anything associated with this whole area—which they consider sacred.”

the molecular breakdown of medical mushrooms

Making psilocybin is sort of like putting together a jigsaw puzzle, one whose pieces have to be assembled in a particular order and for which some pieces fit together only if they’re in the presence of another piece. Putting in one piece can cause another to change shape, or attract a new piece that wasn’t there before. In the end, if you follow the directions correctly, you have a completed puzzle: a psilocybin molecule.

“It’s not a terribly tricky synthesis,” said David Nichols, a medicinal chemist and pharmacologist who has made various psychedelics in the lab for research studies, “for somebody working on a master’s degree in organic chemistry who has some lab skills.” He means that it does take some skill and finesse. Since Albert Hofmann first made synthetic psilocybin in the 1950s, Nichols said that the process has been improved upon, with different methods to attach different chemical compounds and ways to skip a step or two.

Today there are two big-name players already making synthetic psilocybin with the goal of eventually treating people with depression and other mental health issues. One is a for-profit company, Compass Pathways; another is a nonprofit, Usona Institute.

Compass Pathways is a London-based company that received Breakthrough Therapy designation from the FDA for its synthetic psilocybin therapy for treatment-resistant depression, meaning that its preliminary clinical evidence was so promising, the FDA will fast-track its review process.

In 2018, Olivia Goldhill wrote an article for Quartz on how Compass got to that point: Compass Pathways started out as a charity and turned into a for-profit drug company. Goldhill interviewed psychedelics experts who believed that Compass was setting itself up to be a gatekeeper to the psilocybin compound. She also spoke to nine of Compass's advisers, who argued that “Compass Pathways has relied on conventional pharmaceutical-industry tactics that could help them dominate the field, including blocking potential rivals’ ability to purchase drugs, filing an application for a manufacturing patent, and requiring contracts that give Compass power over academics’ research and are restrictive even by pharmaceutical-industry standards,” Goldhill wrote.

Compass has also received flak about its investors, who include the venture capitalist Peter Thiel, the co-founder of PayPal and a vocal supporter of Donald Trump. Rick Doblin, the founder and executive director of the Multidisciplinary Association for Psychedelic Studies (MAPS), has said that MAPS was similarly called out for taking a million-dollar pledge from the Mercer Family Foundation, which is run by the Trump supporter Rebekah Mercer, one of Breitbart News’ main funders.

“Companies investing in psychedelics, of course, will be motivated by a desire to improve the human condition, but they will also be motivated by profit, which invariably will skew things,” Adam Winstock, a medical doctor at University College London, told the Medium publication Elemental in 2019. “That’s the case with the pharmaceutical industry time and time again: Good intentions are marred by the drive to maximize revenue.”

In January of this year, Compass announced that its latest patent, for its methods of treating drug-resistant depression with a psilocybin formulation—had been granted. Lars Wilde, one of the three co-founders of Compass, said that the patents’ purpose is to “protect our innovation,” not to prevent anyone else from making psilocybin. “The question has been raised many times, whether we would stop researchers from doing research and [the answer is] absolutely not,” Wilde told VICE.

“A nonprofit, a for-profit, that doesn’t matter much to me,” Wilde went on. “The idea is that we’re developing a drug, which is a draft product that comes together with both efficacy and safety data. And we’re producing this regulatory approval package in the interest of patients. And so we want to own the process and we want to ensure patient safety and that the therapy is delivered in the right way.”

The Usona Institute, on the other hand, has emerged with a different strategy. It was founded after Bill Linton, the CEO of a life sciences company, had a friend participate in a psilocybin trial at Johns Hopkins University that helped cancer patients with end-of-life anxiety. Usona is a not-for-profit organization funded by investors and donors, and it has decided not to apply for any patents, even though Usona has its own process for making psilocybin, too.

“We support the open dissemination of knowledge and materials in the synthetic realm,” said Chuck Raison, Usona’s director of clinical and translational research. Alex Sherwood, one of Usona’s medicinal chemists, explained to VICE that Usona makes psilocybin available to any scientist qualified to work with it. Researchers can apply to receive psilocybin capsules for free, along with matching placebos, in order to do controlled experiments of their own.

As the competition within psychedelic medicine grows—and Compass and Usona's trials enter phase two of three before getting FDA approval—there will be even more ways invented (and patented) for psilocybin to be produced, and more people trying to come up with efficient and cost-effective strategies.

In 2019, for example, the chemical and biological engineer J. Andrew Jones and his colleagues genetically engineered E. coli bacteria to make psilocybin.

Mushrooms produce psilocybin by pulling nutrients from the environment, then taking those nutrients and forming them into the precursor compounds for psilocybin. Mushrooms also make enzymes, encoded for in their DNA, which act on the precursors to make psilocybin. Jones inserted mushroom DNA in E. coli to give it the same ability to express those enzymes. All the E. coli need is a regular diet of glucose and a hospitable environment, and they produce psilocybin. Jones and his colleagues filed a provisional patent on their process and are working with a startup company to bring it to market.

Developing a drug costs a lot of money, and it’s an open question as to how organizations are supposed to make, test, and market a psilocybin treatment without investors or profits. Should psilocybin be brought to patients only through not-for-profit companies, as Usona is doing? It’s worth asking: Why would we expect it to, when so few other drugs are developed that way?

“The other concern you have with for-profit development is this sort of critique of capitalism, that it’s all about profit maximization and that it doesn’t take into account human needs—it’s all about making money,” Doblin said in a 2018 interview with Psychedelic Times. “I think that’s not the case. From all that I know about Compass and what they’re trying to do, I think they have both financial and humanitarian motives.”

Nichols, the medicinal chemist, isn’t kept up at night worrying about any one entity having a monopoly on psilocybin; psilocybin can be made in so many ways, and Compass’ patent isn’t prohibitive. He said it just involved their use of certain solvents and crystallization methods. He said having a powerful nonprofit like Usona on the scene will likely keep costs down—as long as they remain a nonprofit. (Usona told VICE they don’t like to speculate, but plan to continue being one.)

The truth is, there is money to be made in psychedelics, and investors are flocking to back startups in the psychedelic and mental health spaces. The current antidepressant medication market was valued at $14 billion in 2018 and is estimated to grow to $16 billion in the next three to five years. Any drug company that can compete stands to become very wealthy.

mushroom pills on the factory line

And so the psychedelic community will have to contend with this: Some people might get rich. “People that were in the psychedelic community in the early days had this assumption and feeling that [psilocybin] was something that was going to be made available as a gift to the world, and not as something that would be made available within the structure of big business,” Raison said.

Many have negative views on how pharmaceutical companies develop drugs, and the high prices they put on them later. They don’t want to see that happen to psychedelics. “We naturally want to encourage the proper containers and intentions surrounding these powerful substances and practices,” Wesley Thoricatha wrote in Psychedelic Times. “As such, we tend to be wary of for-profit endeavors, as they can potentially involve ethical compromises for those whose primary goal is profit.”

But Doblin said in the aforementioned interview that he thinks the for-profit development of psilocybin is a sign that all the academic research, nonprofit work, and activism has been effective. “The fact that investors are willing to take a gamble with their money is a sign of success of the nonprofit work—that we’ve cleared out enough of the political, regulatory, and public opinion problems that this can now be like a normal field of science, or at least in that direction.”

To wish to relegate psilocybin to its more traditional, “natural” settings is a privileged stance, according to Wilde. It ignores the reason there’s so much profit potential in the first place: This drug could really help people. “When I think about myself four years ago and when I was suffering from panic attacks and severe depression, I wasn’t a psychonaut,” Wilde said. “I wish there would have been the possibility to go to a psychiatrist and say, ‘Look, I’ve exhausted my treatment options. What else do you have?’”

Besides the influx of money and ownership claims, synthesizing psilocybin and packaging psychedelics into neat capsules that you can pick up from your doctor demystifies something that has for so long been ineffable. A patent for psilocybin production turns it into just another chemical, a collection of atoms that someone with an advanced degree and a knack for working with phosphate groups can make. “Scientists have once again inserted themselves between the natural process and the human organism,” the wellness website Gaia wrote in 2019.

Perhaps there are some lessons to be learned from what happened after Gordon Wasson wrote about María Sabina in Life magazine more than 60 years ago. Celebrities and tourists flocked to Sabina’s town to partake in the drug ceremonies and ended up disrespecting the local culture and traditions. Sabina was blamed for this, and shunned by her own people—her house was once burnt down, and she was investigated by the government as a possible drug dealer. She eventually said, according to her biography, that after the foreigners arrived, the mushrooms had “lost their force, they ruined them. Henceforth they will no longer work. There is no remedy for it.”

Wasson himself expressed regret at how the mushrooms had gone mainstream. In 1970, he wrote in the New York Times:

What have I done? I made a cultural discovery of importance. Should I have suppressed it? It has led to further discoveries the reach of which remains to be seen… Yet what I have done gives me nightmares: I have unleashed on lovely Huautla a torrent of commercial exploitation of the vilest kind. Now the mushrooms are exposed to sale everywhere—in every marketplace, in every village doorway. Everyone offers his services as a “priest” of the rite… In 1955, Maria Sabina asked me hesitatingly for 13 pesos as the price of her services for a night’s work. I have heard that now strangers pay sometimes between 500 and 1,000 pesos for a “performance.”

Medical psychedelics are coming, and the future will need to make space for both recreational and pharmaceutical uses. Hopefully one doesn’t have to destroy the other, and people with different associations with these drugs can find room for those beliefs.

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