Illustration by Philip Lindeman
In his ultra-clean lab gleaming with glass and steel equipment, Miami University researcher Andrew Jones cooks up psychedelic drugs on an industrial scale. When I reach him via Zoom, he sits in front of a whiteboard scrawled with arcane chemical formulae.
His lab looks like Walter White’s, when it began to resemble a craft brewery in later seasons of Breaking Bad. And, in a way, Jones is brewing. He has four two-liter bioreactors in which he ferments e. coli bacteria genetically modified to produce psilocybin, the magic ingredient in magic mushrooms; dimethyltryptamine; and other tryptamines. Those substances are valuable to researchers investigating the pharmaceutical potential of mind-altering drugs.
Interest in psychedelic drugs has reached a fever pitch in recent years. Celebrities, athletes, business leaders, and billionaires have touted the substances’ ability to boost creativity and blow the cobwebs from aging brains. They show remarkable promise for treating post-traumatic stress disorder (PTSD), depression, addiction, chronic pain, and other debilitating conditions. The U.S. Food and Drug Administration (FDA) has granted “breakthrough therapy” status to accelerate research into Ecstasy and psilocybin. In 2020, Oregon became the first state to legalize psilocybin for therapeutic use.
In the summer, Lykos Therapeutics looked to be on-track to gain approval for MDMA (Ecstasy) to treat PTSD-afflicted military veterans, a cohort in which suicide is epidemic. Suddenly conservative politicians and right-leaning billionaires—not the people you would expect to advocate for psychedelics—were voicing support and lobbying the FDA.
In August, however, the government rejected Lykos’s application, citing ethical concerns over incidents and omissions. Two trial participants who committed suicide following MDMA treatment were left out of the Lykos application, as was a trial participant’s description of inappropriate physical contact from researchers.
Following the FDA’s rejection, the journal Psychopharmacology retracted three papers by Lykos researchers. The company constitutes a “therapy cult” say a number of observers, including Johns Hopkins University senior lecturer Nese Devenot, who emerged as a voice of concern over psychedelic research while doing post-doctoral work at the University of Cincinnati.
The FDA decision angered psychedelic therapy advocates, including veterans groups and investors hoping to cash in on a potential new market. Some worry that the move will derail widespread access to drugs that can prevent pain and suicides.
But psychedelic compounds continue to be investigated worldwide, including in Oxford, Ohio. The curious-minded are already traveling to Oregon to take legal psilocybin. And public acceptance of formerly forbidden mind-altering substances is slowly but surely changing.
Recalling certain ad hoc psychedelic experiments from my college years, I ask Jones how much psilocybin his Miami University bioreactors are capable of cooking up, compared to a baggie of ’shrooms. Jones does some quick calculations. “Each bioreactor can produce about a four-gram batch of psilocybin,” he says, “which is equivalent to about 160 25-milligram doses or about 800 grams of mushrooms.”
The technology is scalable, and two-liter vessels can easily be super-sized. That’s attracted drug company attention and funding for Jones, including $2.5 million from one small company. But betting on the legalization of these drugs is risky. Miami is back to looking for new prospective licensees interested in commercializing the technology, he says.
Photograph courtesy Miami University
“We leverage the kind of chemistries that can happen in a mustard plant, bacteria, fungi, humans, animals, plants,” says Jones. Or those that endow the Sonoran Desert Toad with its psychedelic secretions. “We have the ability to mix and match biology to enable these processes in ways that biology can never do by itself.”
Sometimes Jones’s team identifies the operative string of DNA in online databases, he says, “then we copy and paste that DNA and send it to our favorite DNA synthesis company.” They get back a minuscule quantity of that genetic material and clone it into a plasmid, “a circular piece of DNA that can be replicated inside bacteria and express the desired enzyme. We feed the bacteria substrates, and that bacteria will convert them into whatever compound we want.”
Why lab-synthesize compounds that grow in nature? Laboratory production provides a high degree of control over the product, says Jones, making it more consistent and stable. Psilocybin mushrooms are extremely sensitive to their environment, for instance. And synthetics save you from having to catch a bunch of toads.
Jones’s team is also working on creating derivatives of the compounds that aren’t hallucinogenic, which is useful since not every user is looking to get high. In an experimental setting, hallucination-inducing drugs make controlled studies extremely difficult, if not impossible.
“The reality is that studies with psychedelics are hard,” Jones says. “The core basis of a clinical trial is that you give a drug and you give a placebo but both groups think they’re getting drugs.” The idea is to keep patients’ mindsets from influencing the outcome. “But you can tell that there’s a hallucinogenic or psychedelic side effect of MDMA, psilocybin, you name it, so it’s easy to tell which group you’re in as a patient, and that biases the trial results.”
While Lykos’s rejected application for MDMA is a setback for researchers like Jones, he sees the decision in a positive light. “The FDA is approving drugs based on scientific evidence, which is how it’s supposed to work,” he says. “We want to make sure that people know what they’re getting, right? When you use a prescription drug, there’s an understanding that there are going to be known side effects and you’re not going to have unknown negative outcomes.”
The current fracas over MDMA/Ecstasy is only the tip of the psychedelic iceberg. While it’s grabbed headlines for helping veterans with PTSD, the drugs’ potential reaches far beyond mental health.
Jones is collaborating with researchers at the University of Cincinnati on animal trials to explore psilocybin’s ability to promote nerve regrowth, because “psychedelics have this neuroplastic effect that causes an increase in neuron connections,” he says. And the drug is anti-inflammatory, which could be widely applicable given that inflammation is an underlying cause of a number of human diseases.
Jones believes that MDMA, which is more toxic than psilocybin, might not be the best candidate for psychedelic therapies. “I think there’s a lot of evidence that says that psilocybin and other tryptamines, which are a different class of molecules than MDMA, have lower side effects,” he says. “They have no addiction tendency, so you don’t build up a resistance to them. I think the next round of drugs may have a better chance at getting FDA approval.”
Photograph by Psychedelight senses/stock.adobe.com
How did these compounds evolve to weave their strange magic on our minds? One theory is that some fungi became psychedelic as a deterrent against prehistoric slugs. Psilocybin-bearing fungi emerged around the time an asteroid wiped out the dinosaurs and 80 percent of life on Earth, leaving fungi and gastropods to thrive.
Certain psychedelic mushrooms also benefit from attracting insects and controlling their behavior to some extent, writes renowned Miami University mycologist Nik Money, whose latest book, Molds, Mushrooms, and Medicines (Princeton University Press, 2024), includes a chapter on the science and implications of psilocybin-producing mushrooms. One fungus infests cicadas, filling their abdomen with spores and drugging the males so they wiggle like females, thereby attracting more hosts to spread spores.
Then there’s “zombie-ant fungus.” Infected ants are inspired to climb to the heights of plants, where they bite down in a death grip before the fungus explodes from their heads and sprays spores into the air.
We’ll probably never fully understand how mushrooms and fungi come to produce psilocybin, says Money. “What we do know is that psilocybin works with a very specific serotonin receptor in our nervous system,” he says. There’s still so much we don’t understand about these drugs, he adds, and the study of psychedelics is further complicated by the contrasting motives for their use by different classes of user.
“You’ve got the group of people who use them medically, seeking relief from chronic depression, including the despair that comes with terminal illness, as well as for PTSD and addiction,” he says. “Then there are those for whom psilocybin is part of their spiritual practice.”
Finally, there are recreational users.
Money has never tried psychedelics, but he recognizes their therapeutic promise. He’s skeptical of the world-changing possibilities of tripping that some advocates believe in—though he acknowledges that scientist Kary Mullis credited his 1985 Nobel Prize–winning discovery of the polymerase chain reaction (PCR) process to psychedelic use. “He claims that it was during an LSD trip that he actually began to see how this almost miraculous molecular technique would fit together,” he says. The PCR technique has revolutionized scientists’ ability to manipulate DNA, enabling the very biotechnology that Jones uses to make massive doses of psychedelics in his lab.
The use of psychedelic drugs for healing and spiritual practice runs deep in human history. With their rediscovery by Western science, beginning with Albert Hofmann’s synthesis of LSD in 1929, scientists have turned to psychedelics to treat mental health conditions and plumb the mind’s mysteries. Hoffman went on to isolate and synthesize psilocybin and other drugs in the service of creating new pharmaceuticals.
U.S. scientists enthusiastically studied these drugs well into the 1960s. But after 1970, when President Nixon signed the Controlled Substances Act, legal production ceased. Psychedelic drugs, despite their documented promise, went underground.
Money feels that the decision “to ’shroom or not to ’shroom” is personal, but he worries about young people opting in. “And I’m troubled by the opening of clinics in Oregon,” he says. “What would qualify somebody to be a counselor who might guide a young person on their psychedelic experience?”
Eric Lee, M.D., isn’t a psychedelic therapist. But as the owner of Space Psychedelic Clinic in Portland, Oregon, he administers psilocybin to patients, who are guided through the experience by licensed facilitators, who undergo training and must pass an exam and a criminal background check.
Discreet behind a privacy fence and Zen-style garden, Lee’s business is one of approximately 25 legal Oregon clinics where patients take psilocybin under the guidance of licensed facilitators. The clinic’s decor is understated, filled with plants. A pair of puffy beige recliners dominate the treatment room.
Lee, a Cleveland native and former emergency room doctor, says he’s put a lot of thought into the environment, which influences the experience, what practitioners call “set and setting.” The idea to open a psilocybin clinic came to him while he was on mushrooms at a music festival, he says. He’s candid about his recreational use of psychedelics and his belief that these experiences have guided him to discovering new ideas. “But facilitated psilocybin therapy is completely different from recreational use,” he says. “Formal psychedelic work involves a lot of preparation, and, really, no amount is too much.”
Oregon legally requires counseling and preparation before the drug’s administration. Patients must pass a brief health screening. After the trip, they can attend follow-up therapy sessions, termed “integration.”
Lee believes that to have a positive outcome from psilocybin therapy “it’s important to have a clear goal,” he says, “more than just wanting to feel better.” The preparation phase is where clients begin to focus on that goal. Treatment-resistant depression and anxiety are the two biggest issues Lee’s clinic treats. And if you’re coming here to tackle addiction or over-reliance on a substance, you need to have already begun to taper off, he says. Psychedelic therapy should only be part of ongoing treatment.
While on psilocybin at Space Clinic, patients are free to move around the space and even go outside, which, if you’ve ever taken mushrooms, is something you often want to do. But, Lee says, “We want people to turn within, which is to put on a blindfold and get under the blanket and really think about their problems for a few hours. And that only happens when people are fully prepared.”
State law allows psychedelic facilitators to administer up to 50 milligrams of psilocybin, which, in the parlance of the initiated, is a “heroic” dose. Not everyone needs that much, says Lee.
His clients aren’t paying just for legal access to psilocybin; much of the $900 cost of a session at Space Clinic goes to the facilitator. The treatment isn’t cheap, he’s well aware, especially when you factor in the plane ticket for those traveling from out of state.
But Lee contrasts his space with “luxury” psychedelic clinics that have sprung up. He’s one of the least expensive options, he says, because lowering the financial bar to access is important to him. Cost of access is a major concern in the nascent psychedelic therapy field, one of the reasons cited by supporters of MDMA-assisted psychotherapy for speedy FDA approval. Many of those seeking these drugs for mental health reasons are already disproportionately burdened by their conditions, which fall most heavily on the socioeconomically disadvantaged.
Access and safety, Lee says, “are why legal facilitated psychedelics are important. We can exist in broad daylight. People don’t have to tiptoe around or go underground. A lot of mental boxes about safety are checked off. So people can come here and really get into it. I don’t want you to have a mild experience. I want people to really go for it. And you can really only do that when you feel really good about what’s going on.”
While Lee keeps busy serving patients who visit to address mental health issues, psychedelics also show remarkable promise for addressing physical pain. That potential is central in Rutgers University professor Joanna Kempner’s latest book, Psychedelic Outlaws: The Movement Revolutionizing Modern Medicine (Hachette, 2024). She follows an organized effort to resurrect psychedelic medicine by an online group of individuals suffering from what’s considered the worst pain humans experience: cluster headaches, also known as “suicide headaches.”
When news circulated that psilocybin and other psychedelics can stop and prevent the recurrence of cluster headaches, people were soon sharing information on growing magic mushrooms for self-treatment. Because that’s illegal in the U.S., interest snowballed into advocacy and fund-raising for psychedelics research, culminating in clinical trials at Harvard University.
“There’s been a surprising lack of research on the use of psychedelics for pain treatment,” says Kempner, “given that the federal government has poured billions into finding safe, non-addictive alternatives to opioids.” But she’s encouraged by a recent proliferation of studies on psilocybin for pain, including for phantom limb pain, chronic back pain, and fibromyalgia. And LSD treatment for cancer pain is on the horizon, she says.
Interest in psychedelics is at a tipping point in the U.S. There’s monetary investment and bipartisan support on the table. But there’s also an understandable dose of distrust for pharmaceutical companies, given revelations about their role in the opioid epidemic. The recent backlash against ketamine therapy isn’t helping either.
With recreational cannabis now legal in Ohio, some wonder whether psychedelics might be next for the Buckeye State. Some Ohio entrepreneurs anticipate legal psilocybin here, but legislative bodies have yet to entertain the notion.
Ohio State University became the first U.S. college to get DEA permission to grow psilocybin for research purposes. Clinical trials using psilocybin to treat depression are underway there now, as well as at the Cleveland Clinic. For the time being, Cincinnatians seeking a legal psychedelic experience must travel to Oregon.
Some of the fervor for access to psychedelic drugs stems from the desperation of those suffering from a slew of medical conditions. Nese Devenot knows all too well the heated emotions this debate can generate. Doing post-doctoral work in psychedelic humanities at the University of Cincinnati, she’s made waves nationally with warnings that the excitement over psychedelics was leading to outright misinformation and fueling a “psychedelic hype bubble.”
Devenot and Cincinnati-based journalist Russell Hausfeld, who investigates the psychedelics movement, are colleagues in the research nonprofit Psymposia. They consider their own lives to have been improved by psychedelics and want to see medical applications done right.
Devenot started a petition in April calling for an FDA advisory committee to be convened regarding Lykos Therapeutics’s application for drug approval, and after doing so endured social media attacks and was falsely mischaracterized as opposing the medicalization of psychedelics. “This is not anti-psychedelic but a pro-psychedelic perspective,” Devenot says, adding that Psymposia is simply calling for more transparency, rigor, and protections for trial participants.
Hausfeld says he came to Psymposia from a position of wanting to destigmatize and demystify psychedelics. While investigating a death that happened on Lykos’s watch, as well as allegations of sexual assault in their trials, he realized the organization was being less than honest. “I found out they were withholding data,” he says. “And so that was sort of a turning point for me. A lot of people right now are acting as if the FDA’s denial of Lykos’s application is going to derail the entire industry. But the opposite is true.”
Devenot agrees that the FDA’s decision to deny Lykos’s application could be positive for the pharmaceutical industry. “As production is scaling up, it’s going to be really important to address these abuses of power. The whole premise of why we need to scale up so quickly is to fix trauma, and yet the way the field is behaving is actually contributing to trauma,” says Nese Devenot.
Devenot believes too many people are buying into the narrative that psychedelics are going to fix every problem and therefore don’t ask too many questions. “I hear lots of people saying, Get psychedelics out to as many people as quickly as possible, and that’s going to help solve climate change and polarization, the rise of fascism, and all these problems,” she says. “Actually, it’s like we’re sleepwalking into the dystopian future.”
There’s a growing notion that an awe-inducing drug that dissolves one’s ego and gives a vivid sense of the interconnectedness of all things might actually help humanity overcome its differences and make us more environmentally conscious, even kinder. But psychedelics are also what psychiatrist and LSD researcher Stan Grof called “non-specific amplifiers” that magnify what’s already present in the conscious and unconscious mind. Despite all of the controversy and debate, Devenot believes in psychedelics’ potential as a tool for “imagining a world without many of the conditions that are driving all this PTSD in the first place.”
Will the neuroplasticity that psychedelics encourage help us imagine new paths to confront the existential threats facing humanity? Certainly, healing individuals is a step toward healing the whole. Kempner has seen psychedelic medicine save lives. In her book, the quest for psychedelic access becomes a lens to reconsider modern medicine, magnifying its flaws but also showing ways to improve the slow and costly process behind getting new drugs approved.
“Self-experimentation has historically driven scientific progress,” says Kempner. “In the case of psychedelics, self-experimentation has sparked both curiosity and funding. Rather than aiming for perfect objectivity—which may not be fully achievable—we should accept that subjectivity is part of the process.”
The use of psychedelics in research creates a feedback loop where the drugs, pharmaceutical companies, and social context all influence each other, she says. “But good research methods, honesty, and transparency are crucial for managing the complex questions we face.”
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