Making Magic

Doctor Peter Facchini, PhD, got serious about science when he was 16 and bored of the experiments in his Sears Wish Book chemistry set. Instead, he started to conduct “more dramatic” experiments out of his mother’s high school chemistry textbook which was published in the 1950s when, he says, “safety and liability weren’t priorities in youth activities.”

In Grade 11, Facchini’s science teacher assigned him a project to test the effect of electricity on plants. The teacher considered Facchini’s experimental setup too dangerous for the regular lab and locked his equipment in a prep room. Facchini needed to ask for a key every time he wanted to check on his experiment. This wouldn’t do. “I decided it was acceptable to ‘borrow’ equipment for my chemistry experiments at home,” Facchini says. He converted the kitchen in the basement of his family’s Toronto home into a chemistry lab. “I was able to pull off some interesting results.” (Even more interesting results came six years later, when Facchini was working on his post-doc and his mother called him in a panic. The hinges on the basement kitchen cupboard had completely rusted out and the doors had fallen off. She wanted to know what he’d left in the cupboard. “It was probably sulphuric acid,” Facchini told her.)    

After high school, Facchini earned a Bachelor of Science in botany from the University of Toronto and then started postgraduate studies. Two months after he started his master’s degree, Facchini’s supervising professor resigned after the university discovered he’d never completed his doctorate. “It just so happened the initials for his first and second name were DR,” Facchini says. “Someone started calling him ‘doctor’ and he just went with it.” With his supervisor axed, Facchini continued with his collaborator. “This guy happened to be working on medicinal plants,” Facchini says.   

Facchini defended his PhD in 1991 before starting a postdoctoral fellowship at the Université de Montréal where he was involved in a project to reduce the glucosinolate content of canola to make the seeds tastier for picky pigs and cows. The idea was to insert a gene into the canola that would halt the production of glucosinolate in the seed. Facchini asked his supervisor if he could clone the gene from opium poppies — the enzyme catalyzes the first step in the pathway from poppy to morphine. His supervisor slouched back in his reclining office chair, sighed, then sprang forward and opened the side drawer of his desk. “I just happen to have a jar of opium poppy seeds,” he said.

In 1995, Facchini accepted a position at the University of Calgary, where he has been conducting research in opiates, cannabis and psychedelics ever since. Facchini reigns as Alberta’s only researcher with a licence to grow opium poppies and has tended to a garden of poppies in the basement of UCalgary’s Science A building for 25 years. Elsewhere in Science A, Facchini maintains a greenhouse devoted to his cannabis plants and peyote cactus — the source of the psychedelic mescaline. He doesn’t grow “magic” psilocybin mushrooms, but this is only because he doesn’t need to. Facchini developed a way to synthesize doseable amounts of psilocybin, as well as other psychedelic compounds, in the cells of ordinary baker’s yeast and bacteria. “Why bother with the mushroom?” he says.   

Facchini co-founded Epimeron Inc., a private biotechnology firm, out of his UCalgary lab in March 2014. For the first five years, Epimeron focused on producing opiate molecules in yeast rather than from poppies, just as he’s doing with psilocybin. In the spring of 2019, Epimeron merged with another Calgary biotech firm to form Willow Biosciences Inc. Under Facchini’s direction as chief scientific officer, Willow used the same yeast process to biosynthesize cannabinoids, including cannabigerol, considered “the mother of all cannabinoids” for its ability to naturally evolve into compounds like THC and CBD. 

In April 2020, in the middle of the pandemic lockdown, Willow decided to reduce its Calgary-based headcount, and Facchini and his team suddenly found themselves contemplating their futures.  

Psychedelic research boasts a long history on the Canadian prairies. Indeed, it was a Saskatchewan-based psychiatrist named Dr. Humphry Osmond who first coined the term “psychedelic” in 1953 in a poem he wrote for his friend, author Aldous Huxley (best known for his science-fiction novel, Brave New World), after guiding him through a mescaline trip: 

To fathom Hell or go angelic 
Just take a pinch of PSYCHEDELIC 

Two years earlier, Osmond had accepted a research position with his fellow psychiatrist and biochemist, Dr. Abram Hoffer, at the overcrowded Saskatchewan Mental Hospital in Weyburn, one of the largest asylums in North America. Hoffer secured grant funding from Premier Tommy Douglas’ government to examine the effectiveness of LSD and mescaline as drugs for treating schizophrenia and alcoholism.

Work by Hoffer, Osmond and colleagues in labs worldwide led to a revolution in brain science and psychiatry that lasted through the 1960s — but the party ended once the parties started. The drugs inevitably drifted out of the labs and into the counter-culture, and recreational use of psychedelics overshadowed their research potential. As the drugs became associated with anti-establishment movements — especially among anti-Vietnam War activists in the U.S. — governments began to regard psychedelics as more menace than medicine. The UN Convention on Psychotropic Substances banned psychedelics globally in 1971, and medical research effectively ceased for more than 30 years.  

Psychedelic science was resurrected in 2006 when researchers at Johns Hopkins University School of Medicine showed a single high dose of psilocybin had long-lasting positive effects on a patient’s mood and sense of well-being. The study sparked an ongoing renaissance of psychedelic research, especially in the last decade.

By the end of January 2021, the U.S. National Library of Medicine’s ClinicalTrials.gov website showed 59 psilocybin drug trials had been registered worldwide. These studies pit psilocybin against a wide range of conditions including depression, anorexia nervosa, cluster and migraine headaches, PTSD, alcoholism, and disorders linked to cocaine and opioid use. If the outcomes of such tests prove positive, psilocybin could soon emerge as a licensed medication for multiple forms of mental illness.   

Perhaps it was no surprise, then, that Facchini and his locked-down colleagues didn’t stay unemployed for long. “I sat in my backyard, drank a lot of beer, thought about psychedelics, had a lot of Zoom calls, and said, ‘To hell with it, let's start another company!’” Facchini says. “Opportunity knocked.”

A Toronto-based investment banker familiar with Facchini’s work wanted to launch a new biotech firm focusing on psychedelics. The investor had confidence in the team’s broad experience, Facchini says, “not just in the science with the things we’d done before, but also in our business savvy.” What had started out as a thought experiment by Facchini and his crew at the beginning of April 2020 was incorporated as MagicMed Industries by the end of May and had secured $30 million in commitments from investors by the end of the year. In February 2021, Business Insider magazine ranked MagicMed the fifth highest money-raising psychedelic startup in the world.

Facchini confesses to not understanding the psychology of venture capitalists. “I became a scientist to avoid dealing with lawyers and businesspeople,” he says. Still, he wonders if the pandemic-stalled economy inspired investors. “Investors need an active economy; they need money to be moving to do what they do. And so, they were looking for these opportunities.” Especially, as it turns out, in the medical psychedelic space. Investors are pouring hundreds of millions of dollars into the sector. “We’re capitalizing on it,” Facchini says. “We have business savvy, but it’s also a pretty easy sell. And we’re one of the few companies that actually has hardcore science behind it.”

Facchini says MagicMed’s approach of responding to market demand differs from the usual academic model “which is, ‘If you build it, they will come.’ They usually don’t. “There are still people who feel academia should be this pure, ivory-tower endeavour. If you are trying to make money from your research, then it’s dirty.”

But, in order for universities to remain relevant to the world off-campus, they have to emerge as economic engines. Facchini says he believes the kind of market-focused research MagicMed engages in could drive the post-pandemic recovery in Alberta — especially in the wake of a collapsing energy industry. The province may turn to academia to create new jobs in new sectors. “The university is saying we should lead,” Facchini says. “You have to start by being supportive of the trailblazers.”

UCalgary’s new Parker Psychedelic Research Chair, established earlier this year by alumnus Jim Parker (BA ’90), demonstrates the university’s commitment to innovation in the psychedelic field. The Chair will launch a psychadelic  research program within the Mathison Centre for Mental Health Research & Education at the Hotchkiss Brain Institute (HBI) to consider initiatives targeted toward improving mental health. Under this program, UCalgary could emerge as world a leader in psychedelic research.

That said, market enthusiasm for psychedelics will eventually abate; investors showed similar excitement for cannabinoids only a few years ago, but then the bubble burst. “Cannabinoids are mostly yesterday’s news,” Facchini says.

The “mushroom boom” won’t last forever, either, and many of the new psychedelic startups won’t be around in a few years. “I have no delusions about what to expect,” Facchini says. MagicMed needs to raise as much capital as quickly as possible and position itself in terms of partnerships and acquisitions. “You want to be one of the survivors as opposed to some of these companies that aren’t going to be here a year from now.”

In the meantime, important science needs to be done. Researchers remain uncertain how psilocybin and other psychedelics function. A U.K.-based scientist has been using MRI scans to observe what parts of the brain light up with psilocybin and determine the mechanism of action. Evidence suggests that psilocybin and other “classic” psychedelics like LSD and mescaline bind to particular serotonin receptors. The drugs likely disrupt brain circuits and systems that encode rumination — the sort of repetitive thoughts and behaviours that characterize a range of mental illness, from depression and addiction to anorexia.

Facchini and his team at MagicMed are working at developing derivatives of psilocybin to create what he calls a “psy-brary” of novel molecules that can be patented and tested for their clinical effectiveness. 

HBI director Dr. David Park, PhD, is keen for members of the institute to work with MagicMed and the psilocybin derivatives they eventually isolate. “We can act as matchmakers to see what researchers within HBI would be interested in some of the novel compounds generated by MagicMed,” Park says.

The Mathison Centre, HBI’s mental-health research arm, can facilitate both animal studies as well as clinical trials important to understand how psilocybin and/or its derivatives may affect mental health.

HBI is excited about collaborating with a startup as local as MagicMed — whose labs are literally up the street — and the psychedelics’ potential as a treatment for a variety of mental-health conditions. But, despite the anecdotal evidence supporting the effectiveness of whole-plant psychedelics, their long history as recreational drugs, and the enthusiasm for MagicMed’s novel compounds, Park cautions against moving too quickly. “You can’t shortcut science,” he says.

Business Insider magazine ranked MagicMed the fifth highest money-raising psychedelic startup in the world.

If Facchini, Park and their scientist collaborators occupy one end of the medical psychedelic chain, palliative-care physician Dr. Lyle Galloway, MD, a clinical lecturer in the Department of Oncology, stands at the other. Galloway first encountered psychedelic mushrooms when he was in his early 20s, while travelling abroad. “It was a profound experience,” Galloway says. “I had a big-dose experience right off the bat that gave me a considerable amount of respect for what these medicines can do.” Galloway bought some books on how to cultivate mushrooms and ordered himself some mail-order spores. “I got reasonably good at growing psilocybin mushrooms,” Galloway says. “And then I got married and had kids and then life went on.”

After decades of dormancy, psychedelic mushrooms have bloomed in Galloway’s professional life over the past few years. Research started to emerge suggesting psilocybin can have a role in alleviating what palliative-care physicians refer to as “existential distress” — one of the most difficult forms of suffering to treat. “Supportive counselling helps to some extent, but talk therapy only goes so far,” Galloway says. Two simultaneous studies published in 2016 from New York University and Johns Hopkins showed patients with end-of-life depression and anxiety responded dramatically and rapidly to a single treatment with psilocybin. 

The studies hardly surprised the many therapists who’ve long been working outside the law with psilocybin and other psychedelics.  “There is a wealth of experience out there with underground therapists who’ve been working for years — decades, in some cases — with these medicines,” Galloway says. “That’s not really acknowledged.” 

Galloway, though, sought more official training. In 2019, he enrolled in the year-long Psychedelic-Assisted Therapies and Research certificate program offered by the California Institute of Integral Studies. The program's faculty included scientists who performed much of the original research on therapeutic psychedelics in the 1960s and 1970s.

Galloway, a clinician-scientist who is currently collecting data to inform future practice and research, has had a number of patients ask him about possible use of psilocybin in their own cases, often having heard about it in the news or through support groups. Galloway makes sure these patients understand that the science of medical psychedelics is relatively new, and that while he believes the treatment is safe for most patients, careful screening is necessary and there may be side effects the medical community doesn’t yet know about. If patients are interested in pursuing this option, Galloway will discuss the evolving process by which they can apply for an exemption, and ensure they are connected with appropriate medical and psychotherapeutic supports to proceed safely.

Once granted an exemption, the patient must seek out his or her own supply of psilocybin mushrooms. Unlike cannabis products that can now be legally purchased in specialty shops in nearly every neighbourhood, psychedelics remain illegal. Still, patients have little trouble sourcing them. Even those with no street contacts or any experience with recreational psychedelics easily manage to score mail-order ’shrooms online. “I have patients in their 60s who went online and, without substantial Internet knowledge, ended up with therapeutic quantities of mushrooms in their mailbox,” Galloway says.

Galloway then encourages his patients to bring their newly acquired mushrooms into the office for a formal, supervised therapy session. However, psychedelic-inspired healing does not rely on the presence of a therapist. “Essentially, the real healing comes from the patient — it comes from inside,” Galloway says. “However, a trained therapist can function as a guide for the experience. Someone familiar with the territory [who] can help make sense of what happens.”

Unlike drugs that serve to blunt consciousness, psychedelics can bust down all the doors. “These medicines need to be approached with a certain amount of respect, or even reverence,” Galloway says. Trips are rarely pleasure cruises to a patient’s happy place. “A psychedelic experience can be extremely scattered and extremely scary,” Galloway says. While patients can enjoy some fun and levity during their psychedelic session, the experience is often agonizing. Long-buried grief and unprocessed guilt can erupt unexpectedly.

One of Galloway’s palliative colleagues observed one patient endure such agony during her psilocybin treatment that the therapists who witnessed the experience also suffered distress. “They even arranged a debriefing for all the staff on the unit,” Galloway says. “Sometimes it goes this way.” The patient, though, woke the next day needing half of the pain medication and none of the sedatives she’d been using before the session. After meeting the therapist for one post-psychedelic “integration work” appointment, the patient “went on with her life,” Galloway says. “She was able to address her end-of-life issues in a straightforward way that she never was able to before.”

Despite such anecdotal successes and hours-long therapist-led sessions, Facchini questions their practicality. “Imagine if every time you needed to take an antibiotic, you had to sit for four hours in the doctor’s office,” he says. “You need medicines that are going to be prescribable.” This is what MagicMed aims to produce in its labs. Clinical trials will eventually show whether or not the psilocybin derivatives MagicMed isolates can still function as effective medicine — if they bind to the appropriate receptors, say — without inducing psychedelic effects. In other words, will his novel compounds allow a patient to reach their therapeutic destination without taking the trip?

Galloway, while admiring Facchini’s lab work, suspects the trip is necessary. “Most people in my field are not that excited about the discussion of receptors,” Galloway says. Questions about biochemical pathways, dosing and other such factors appear less important in psychedelic-based therapy than what Galloway calls the mystical experience. “What seems to be linked to a positive outcome is having a transcendent sort of experience,” he says. “There is something about the experience of leaving your ordinary consciousness for a period of time, then returning, that taps into a profound healing potential.” He says the psychedelic trip grants patients suffering from end-of-life distress a “50,000-foot view” on their “small self.” From that height, they can tap into something larger, whatever that might be.

Mystical, though, doesn’t mean religious. A psilocybin trip is not necessarily a commute with God. Avowed atheists benefit from these therapies without emerging as believers at the other side. Still, the experience does touch patients at the spiritual dimension of their existence in the same way meditation, chanting and devotional dance has for the followers of traditional faiths. All these experiences can help someone access elevated states of consciousness, Galloway says. “But the ability to go so far away from your ordinary state of consciousness and return within a number of hours is unique to psychedelics.”

The idea that Facchini’s molecules might allow patients to bypass these sessions fascinates Galloway: “Would it be possible to develop a molecule that rewires patterns in the brain and allows insight? One that drops you back into your life without any therapy involved? Maybe. I don’t know.” Clinical testing of Facchini’s novel compounds may eventually answer these questions. 

In the meantime, Galloway and his colleagues in the field weigh the actual therapy component heavily. “We look at the psychedelic as the catalyst for the therapy,” Galloway says. An introspective patient who is a disciplined meditator, say, might be able to make some progress with psilocybin on a solo trip. “But there’s something about having an objective third party in the room who gives a good perspective and can guide things in a helpful direction.”  

The emergence of psychedelic medicine may do more than treat existential distress in patients; it might cure a sense of disillusionment among the palliative-care professionals themselves. Galloway figures half of the palliative-care physicians he knows have grown cynical about the work. “You can say we’re treating depression and anxiety, and we do that, or at least pretend to do that, with existing medications and therapies,” Galloway says. “But we were worried that we weren’t doing much good.” Galloway had grown so disheartened with the work, he contemplated quitting psychiatry altogether. “Then [psychedelic medicine] came along and revolutionized things. The reason why I got into psychiatry was because I wanted to help people in the way I am seeing this help people.”

As psychedelic medicine inches gradually into the mainstream, Galloway hopes his fellow practitioners talk openly about their own experiences with psilocybin. “A year ago, I wouldn’t have admitted I was good at growing mushrooms when I was in my 20s,” Galloway says. “Now, I am more comfortable. The fact is that these medicines have been used by responsible people in the real world for decades, if not millennia, and are not causing damage all over the place.” He says he believes more open conversation about use of these medicines by both patients and therapists will be beneficial. 

In addition to assisting patients access therapeutic psychedelics, the non-profit coalition TheraPsil has been working on obtaining psilocybin exemptions for their physicians and therapists. Health Canada granted at least 19 such exemptions for health-care professionals in December 2020, and more are forthcoming. “I hope this becomes the norm in order to qualify to be a psychedelic therapist,” Galloway says. “I don’t believe you can do a good job without having some personal experience."

Trips are rarely pleasure cruises to a patient’s happy place.

For his part, Facchini cares little about the approval of mainstream science. He’s built a career out of researching compounds many consider illicit. “I’ve never been concerned about what someone else is going to think,” Facchini says. Tut-tutting conservative academics who would shy away from such research baffles him. “The whole idea of tenure is you’re supposed to be able to push the boundaries, as long as you’re not breaking the law or harassing anybody,” Facchini says. “You should be taking risks, and those risks are what pay off.”

Many of Facchini’s medical psychedelic colleagues were first drawn to the field by their own experimentation. “I’ve heard from others in the sector say, ‘I went somewhere in South America and did ayahuasca and it changed my life,’” Facchini says.

This is the sort of origin story many people expect Facchini to tell. Facchini, though, resembles the 16-year-old kid in his kitchen chem lab more than a retired drug-tourist in a lab coat. He is no more fervent about psychedelics than he is about morphine or E. coli. “I am not passionate about psychedelics — I am passionate about the science,” he admits. “I’m passionate about how the applications of the science can impact people in a positive way.

“I want to be Elon Musk and make rockets that actually take off and land. I want to make these things work.”

Trippy Roots

The earth abounds with chemical compounds intended to deter herbivores, protect against pathogens and other clever tricks of nature — for humans, however, such psychoactive plants can have mind-altering effects

Mushaboom

What makes a mushroom magic? Psilocybin is a psychedelic compound occurring naturally in more than 200 species of fungi. In humans, psilocybin has hallucinogenic effects similar to LSD and mescaline including a sense of euphoria, changes in perception and a distorted sense of time (think Alice in Wonderland). 

Wile E. Peyote

Used for thousands of years by Indigenous tribes for healing and religious purposes, peyote is a small cactus that grows in the American southwest, Mexico and Peru. Effects of its hallucinogenic substance, mescaline, include a loss of ability to think rationally and a feeling that time is passing more slowly than it is.

Cogito, Ergot Sum

Not the sexiest of backstories, ergot is a parasitic fungus that grows on rye. Discovered by Swiss chemist Albert Hoffman in the 1940s, ergot contains a compound from which lysergic acid diethylamide (a.k.a. LSD) can be derived. “Bicycle Day” (April 19) marks Hoffman’s legendarily trippy bike ride home after trying the drug for the first time.

Mornin’, Glory

The common name for more than 1,000 species of flowering plants, morning glory seeds contain ergoline alkaloids that can produce a similar effect to LSD when taken in large doses. Their use dates back to ancient Aztec and Mayan tribes whose high priests would consume the seeds to trigger vision quests. 

Potent Brew

A brew made from various ingredients including caapi vine, which grows in the Amazon region, ayahuasca has long been used by traditional healers in several South American countries, and it plays an important role in some religious ceremonies. According to current research, its psychedelic properties may protect brain cells and stimulate neural cell growth.

Big Chew

A perennial rainforest shrub growing in Central Africa, iboga’s roots and bark contain a psychoactive alkaloid that induces a profound psychedelic trance state when consumed in large doses. Its taste has been described as “like sawdust laced with battery acid.”

Salviation

A member of the mint family, salvia is a psychedelic herb whose leaves contain opioid-like compounds. It’s fast-acting and, anecdotally, when chewed, smoked or imbibed in tea, can produce a particularly unpleasant experience.  —JM