Feeding on decomposing organic matter, the mycelium will eventually send up fruiting bodies – the familiar capped forms most of us know as mushrooms – laden with a new generation of spores.

Neumann is the lead mycologist at Numinus Wellness, a Canadian company that’s a leader in the pharmaceutical industry’s least likely new subfield. For centuries, humans have foraged forest floors in search of the wild and glorious unpredictability of a psychedelic trip. Neumann’s job is to tame that chaos.

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This spring, deep in a nondescript warren of lab spaces in a strip mall on Vancouver Island, she opens a refrigerator full of Petri dishes and Mason jars with mycelium at varying stages of development. “That’s what I am looking for,” she says, holding up a sample with particularly thick strands.

That initial appraisal is the first step in a painstaking winnowing. From her spore prints, Neumann will cultivate mycelium, growing promising candidates into mushrooms to analyse their vigour and chemical payloads, repeating this step over and over to eliminate any doubt and adding the best specimens to her company’s cell bank.

This six-month-long verification is just one step in Numinus’ magic mushroom optimisation process. Researchers there are experimenting to find what makes the best food for their Psilocybe cubensis; when it is best to extract the primary psychoactive compound, psilocybin; and how finely to grind the fungal tissue when turning it into a shelf-stable powder.

The extract will be tested for impurities, then go into a capsule with a proprietary mixture of stabilisers and other ingredients. If all goes according to plan, a version of this pill will be swallowed with a sip of water in a clinic under a therapist’s watchful eye and paid for by health insurance.

In the United States, veterans’ organisations and former Texas governor Rick Perry are among their champions. The US Food and Drug Administration (FDA) has classified psilocybin as a “breakthrough therapy”, a designation intended to speed the process of getting especially promising drugs to market.

A small February study in the Journal of Psychopharmacology by researchers at Johns Hopkins University found that psilocybin-assisted therapy relieved symptoms of depression for at least a year in 75 per cent of participants and effectively eliminated the symptoms in more than half of them during the study period.

A clinical trial conducted from 2018 to 2020 gave MDMA-assisted therapy to war veterans, sexual assault survivors and other sufferers from severe post-traumatic stress disorder, a notoriously treatment-resistant condition: after three sessions, two-thirds no longer met the diagnostic criteria for PTSD, an unheard-of finding. The FDA has issued breakthrough status to MDMA as well.

All of this comes at a time when the pandemic and the resulting societal disruptions have sharply driven up rates of depression and anxiety and laid bare the inadequacies of the current tools and institutions available to treat them.

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As a result, what once was a scene is now an industry. There are more than 50 publicly traded psychedelic companies listed on US exchanges alone, and start-ups are sprouting all the time.

Proving the drugs work, however, may turn out to be the easy bit. In some ways, money and mainstream acceptance have divided the psychedelic world. Some champions of the drugs are now questioning how they are seeing things unfold.

“The concern that I have,” says Payton Nyquvest, CEO of Numinus, “is that if we’re too quick to just open up access, knowing human beings and the way that we operate, we could miss the therapeutic opportunity.”

Modern psychedelic research began in 1938, when LSD was created in Switzerland, at Sandoz (now a division of Novartis). A few years later, Albert Hofmann, the young chemist who had synthesised it from a grain fungus, discovered the chemical’s euphoric effects when he accidentally ingested some through his skin.

In 1955, a mycology-obsessed American couple named Valentina Pavlovna Wasson and R. Gordon Wasson travelled to a village in Oaxaca, Mexico, where they became the first outsiders to participate in magic mushroom ceremonies dating to pre-Columbian times. Gordon Wasson’s account of the experience in Life magazine two years later was a sensation.

Over the next few decades, more than a thousand scientific papers would be written about the mysterious chemicals, and everyone from actor Cary Grant to musician Charles Mingus to Alcoholics Anonymous co-founder Bill Wilson evangelised their therapeutic potential. (The CIA, hoping to find a truth serum, infamously carried out its own “research” into the drug.)

In the 1950s and early ’60s, tens of thousands of patients would receive psychedelics for depression, alcoholism and other conditions. Research centres arose in California and, improbably, the Canadian province of Saskatchewan to study and train people in new therapeutic methods.

The Czech psychiatrist Stanislav Grof argued that psychedelics could be as valuable for psychiatry and psychology as the microscope and telescope were for biology and astronomy.

But with the backlash against the drugs in the late ’60s, the opportunity to prove (or refute) Grof’s claim disappeared. The Controlled Substances Act of 1970 effectively outlawed studying the human effects of these compounds in the US. When people talk about the psychedelic renaissance, these were the preceding dark ages.

The monastics guarding the flame were a small network of therapists who continued to work in secret – what Michael Pollan, in his 2018 bestseller, How to Change Your Mind, called “the psychedelic underground”. By the 1990s, a few determined researchers in the US, Germany and Switzerland had found ways around the barriers to working with psychedelics.

One of them, psychiatrist Rick Strassman at the University of New Mexico, argued to regulators that studying these drugs could help characterise and perhaps even treat psychotic disorders such as schizophrenia.

This is how traditional antidepressants work, too. But unlike those drugs, a single dose of psychedelics, in combination with therapy, can seemingly relieve the symptoms of mental illness for months.

One of the leading researchers in the field is Robin Carhart-Harris, a professor of neurology and psychiatry at the University of California, San Francisco. In a series of recent papers, Carhart-Harris and his team have used brain scans that track blood flow and electrical activity to monitor the mind on psychedelics.

Their work suggests that something called the default mode network – a collection of brain areas that together function as the command-and-control apparatus – is quieted by psychedelics. The tight, efficient choreography of neuronal communication that comprises normal thought becomes temporarily disorganised, allowing for patterns of connection that an active and alert default network would forbid.

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This cross-wiring can spark hallucinations, or it can just lead to new kinds of thoughts. With depression, some research suggests this profusion of connections leads to feeling better.

And some of these new patterns seem to stick, at least for a while. One Carhart-Harris study this year found that, for people with depression, increased brain connectivity and flexibility from psilocybin were still present three weeks after the therapy, as were the improvements in symptoms. Other studies found effects lasting longer.

“We’ve now got out to 100 days after a single treatment, and we see really no decrease in outcome measures,” says Charles Nichols, a professor of pharmacology at Louisiana State University, referring to his lab’s animal studies. “We’ve moved now from sort of just characterising the clinical effects. We’re delving deeper into the cell.”

Work like this costs money. For years, much of that came from the Multidisciplinary Association for Psychedelic Studies (MAPS), an organisation founded by the indefatigable Rick Doblin, who unsuccessfully petitioned the US Drug Enforcement Administration to stop the criminalisation of MDMA in the mid-80s. In 2000, MAPS began clinical trials to test MDMA’s efficacy for treating PTSD.

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“For 36 years, we have been entirely powered by philanthropy and grants. And that is now changing,” Doblin says. “You could say that we’re a victim of our own success.”

Buoyed by their dramatic PTSD results, MAPS has started raising money for a second phase III clinical trial that’s set to wrap up in the autumn – the final hurdle before the FDA will consider MDMA for medicinal use.

To do so, the organisation has created a US$70 million special-purpose investment vehicle in collaboration with Vine Ventures, one of a host of specialised venture funds trying to get in early on the psychedelic boom. In June, Vine enlisted the auction house Christie’s to raise US$1.6 million for MAPS through the sale of a batch of non-fungible token art.

In a community long dominated by true believers, however, the possibility of profit is a new and destabi­lising force. Hence the controversy around Compass Pathways.

Initially founded as a non-profit mental health company, in 2015, Compass funded important early research projects and had the vocal support of Doblin and several prominent psychedelics researchers. Then, in 2018, it began taking out patents, mostly concerning a specific form, or polymorph, of synthesised psilocybin.

It also filed patents for a psychedelic therapy technique, going so far as to claim that aspects of clinic decor – “soft furniture”, “muted colours”, “a high-resolution sound system” – are, because they are key to Compass’ proprietary therapy, therefore proprietary themselves.

Compass’ executive chairman and co-founder, George Goldsmith, defends these moves as the best way to bring treatment to the masses. Compass, he argues, has the potential to transform mental health, but not if it cannot make money.

“The cost of doing that at scale through a regulated model is unfortunate but true,” he says. “There’s no way to do discounted clinical trials.” The company’s critics, he argues, are part of a “cult”.

For those critics – among them former supporters – this newly aggressive intellectual property strategy threatens to throttle the nascent market. “This is a bit like somebody saying we’re going to patent the phrase ‘Hail Mary’,” says investor and philanthropist Carey Turnbull, who founded the non-profit Freedom to Operate to contest the company’s claims.

Experts in physical chemistry and crystallography that his group hired found Compass’ synthesised molecule was not, in fact, new, but a patchwork of older polymorphs. In June, the US Patent Trial and Appeal Board denied Turnbull’s petitions for “post-grant review” of Compass’ patents.

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Compass went public on September 18, 2020. On the first day of trading, it attained a market value of nearly US$1 billion. Last December, after the company presented the results of its largest trial of psilocybin therapy to date, its stock price peaked at US$58. The trial results, however, were mixed.

Patients with treatment-resistant depression who received a dose of Compass’ psilocybin drug COMP360 all saw a significant improvement in symptoms. About one-third of patients in a high-dose group showed a decline in the severity of their depression after 12 weeks. But so did 10 per cent in a control group. (A quarter of patients in the high-dose group no longer appeared to suffer from depression at all.)

The trial also raised safety concerns, with some participants experiencing suicidal impulses. “There’s been theoretical fears that the nature of the ‘trip’ might be beneficial for many but problematic for a subset,” Paul Matteis, the managing director for biotech equity research at Stifel, wrote in a research note. Compass’ stock has declined over the past year and a half and was worth about US$12.63 in late September.

People in psychedelics tend to be there because of their own experiences. The first three decades of Nyquvest’s life were characterised, in equal measure, by chronic pain and extraordinary powers of compartmentalisation. The pain he traces to his birth, which was premature and marked by multiple complications. His childhood, in his description, was “traumatic” and he developed constant, mysterious gut pain.

Nonetheless, by his late 20s, he was well along in a successful career in finance, running the Vancouver office of a brokerage firm and focusing on investments in novel industries – cannabis being particularly hot.

And yet his pain was landing him in the emergency room two or three times a week, where he received the only intervention that seemed to help: injections of the powerful opioid hydromorphone. He eventually realised his body had grown dependent on them.

In 2018, having come across accounts of people with similar symptoms who claimed to have been cured by psychedelics, Nyquvest booked a stay at Rythmia, in Costa Rica, for a healing ritual with a plant-based hallucinogenic brew called ayahuasca.

An “all-inclusive, luxury, medically licensed plant medicine centre”, Rythmia offers yoga and a restaurant featuring locally sourced food. Its website features video testimonials from the star surfer Kelly Slater and the famously troubled singer-songwriter Bobby Brown.

For Nyquvest, the stakes were very high. “When I flew down, I made up my mind that if this wasn’t going to work, then that was it,” he says. “I was going to take my own life.”

Along with 90 other Rythmia guests, he dressed in white, lay on a mat in a large, open-air room, and drank the potion for four straight nights. On the second, he recalls, everything suddenly went dark.

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He looked down to see his stomach and intestines exposed to the open air, and he felt a hand reaching down his throat and rearranging his insides. Then, he recalls, he had a vision of himself as a newborn, “back in the incubator and healed”. He says he has been symptom-free since.

In starting Numinus, Nyquvest says, “all I really wanted to do is create more access”. But, life saving though it may have been, his own experience is far different from the kind of therapy he is trying to bring to the masses.

He is sitting in a therapy room at one of the three Numinus locations in Vancouver – there are others in Montreal, Toronto, Utah and Arizona. The modern furniture is soft, the lighting is muted and the sound system seems high-resolution.

Nyquvest is critical of the Compass approach, albeit in the non-confrontational tone one might expect from a Canadian psychedelics entrepreneur.

“My concern is that it is getting in the way of accessibility,” he says. “There’s a lot of resources that have flowed into the space to try and create some novel product to be controlled and exploited for, you know, financial benefit.”

But there’s another end of the spectrum, and he is leery of that, too. Some long-time therapists and activists believe medical authorities and regulators shouldn’t have the power to keep these compounds from people who believe they need them.

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“I’ve experienced very deep healing and spiritual insight,” David Bronner says of his own extensive psychedelic experiences. Bronner leads Dr. Bronner’s Magic Soaps, the organic soap and personal-care company his grandfather founded, and he is a long-time supporter of MAPS research.

“It helped me grapple with and rise above some toxic masculinity and just be a more empathic, connected, compassionate person.” He thinks just about everyone should have the same chance.

In 2023, Oregon will become the first US state with widely legalised psychedelics. A November 2020 ballot initiative gave the state’s health agency the task of overseeing magic mushroom consumption at “service centres” in the presence of “licensed facilitators”.

At present, California, Colorado, New York and Washington are all considering some form of legalisation, while several others are enacting decriminalisation. And ketamine therapy is already legal.

Like MDMA, ketamine isn’t a classic psychedelic – its dissociative, trancelike effects have made it popular as both a legal anaesthetic and an illegal club drug. But a robust body of research literature has also shown that ketamine-assisted therapy can reduce the symptoms of depression.

Some companies now offer at-home ketamine therapy, mailing the tablets to patients who are supposed to take them under remote supervision.

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The risks are obvious. Ketamine is addictive. According to the best available evidence, MDMA, psilocybin and LSD are not – and the classic psychedelics also seem to carry a very low risk of side effects. But psychedelics can nonetheless be dangerous.

Those at risk of a severe psychiatric disorder should avoid them, and even perfectly healthy people in the midst of hallucinatory moments of clarity can, if unchaperoned, get themselves into trouble.

“All we need is one story of some minor that did a bunch of psilocybin and got behind the wheel of a car and killed somebody,” Nyquvest says. “One story like that, and it is over, right?”

Numinus itself offers ketamine therapy in its clinics. It also offers drug-free talk therapy and something called “psychedelic integration”: helping patients seeking out the drugs on their own to prepare for the experience. And Numinus is technically allowed to offer true psychedelic therapy in rare cases under Health Canada’s Special Access Programme, which as of this year allows physicians to request the treatment for patients with serious or life-threatening conditions.

The company remains small – clinic revenue in the most recent quarter was less than US$1 million. More than the money Numinus generates, though, Nyquvest is focused on having the necessary infrastructure in place as soon as regulators give their blessing to the new treatments.

The cycle ends with an integration session after the drug’s effects have worn off to try to make some sense of what has happened. In between, there’s the medicine session itself, when the patient takes the drug and puts on an eyeshade and headphones, and the pre-discussed music plays.

“Emotions will arise, images will arise, thoughts will arise that are bigger, deeper, broader, more meaningful than a regular therapy session,” says Joe Flanders.

A psychologist and investigator in the MAPS MDMA clinical trials, he has worked at Numinus since 2021, when it acquired his Montreal-based company, including two clinics offering ketamine therapy.

As vice-president for psychology, he is in charge of training Numinus’ therapists. The company employs 110.

In Flanders’ description, the goal of the therapy is not to unearth Rosebud-like insights for the therapist and the patient to talk through. “We’re relying much less on active, conscious, cognitive processes,” he says.

Psychedelic therapy, rather, is an “experiential modality”, where what happens – whether it be a new-found sense of self-acceptance or a lessening of existential fears – happens at an emotional or even sensory level.

“Getting underneath verbal processes is really important,” Flanders says.

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The psychedelic therapist’s job, therefore, consists of helping someone incorporate these strange, intense new sensations. The patient needs to feel comfortable enough, despite the flood of surreality, to surrender themselves to it.

“You are going into a state of consciousness with lots of vulnerability,” Flanders says. “And so you really need to make sure you’re going to trust the person sitting across the room.”

At Numinus, as elsewhere in the industry, everyone is acutely aware of the importance – and risks – of trust. In 2019, MAPS announced it was terminating its relationships with two of its trial investigators, a married couple who allegedly had a sexual relationship with a participant after working with her.

In July, Health Canada suspended one trial site conducting an independent MDMA investigation for which MAPS supplied the study drug, citing patient safety concerns. (Regulators also found MAPS was in violation of standards for good clinical practices, though it was allowed to continue its trials with proposed corrective actions.)

In addition, MAPS has faced criticism that its research overstates the benefits of psychedelics. Participants in the MDMA trial told New York Magazine that, despite being counted as successfully treated in the results, they continued to struggle with mental health issues throughout their treatment. And though they did make progress with their PTSD, some ended up feeling worse.

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As for Numinus, it does need to make money. Like Compass, it has an intellectual-property strategy, albeit one that tries harder not to offend the ethics of the psychedelic underground.

“We think psilocybin will probably just be generic, and clients will have the choice of what product they would like to use,” says Nyquvest. “And we believe that there’s going to be a number of people that would prefer a natural event.”

Last year, Numinus filed for a US patent on techniques to rapidly produce natural psychoactive fungi species, and it has also filed a similar patent internationally.

Numinus’ next group of patents will focus on the delivery mechanism for the drugs. In addition to a pill, it is exploring liquid formulations and a tea. The company is also licensed to work with LSD, DMT and mescaline in its lab, and eventually it may explore the therapeutic potential of those drugs.

“What we’re seeing right now is only the first generation of these drugs,” says David Olson, a neurochemist at the University of California, Davis. “The third generation will be completely new compounds.”

Olson is among those who believe the psychological component of the drugs’ action is not as important as other, subtler biological effects. In a 2018 study, Olson’s lab demonstrated the neuroplasticity of psychedelic compounds including psilocin (the psychoactive compound the body turns psilocybin into), along with LSD, MDMA, DOI, DMT and ibogaine.

The drugs seem to heal brain cells, reforming weakened synaptic connections. That could help explain why they appear effective for conditions as diverse as alcohol abuse, depression and PTSD, all instances where neurons have atrophied.

But if neuroplasticity is the source of the drugs’ healing powers, that puts in question the role of the trip – the mystical communion that has for thousands of years defined the experience of the compounds. Olson suggests it might, in fact, be unnecessary.

He theorises that it would be possible to remove the psychedelic qualities and have the drugs still be effective. “I am very supportive of people bringing these to the clinic,” he says of the existing hallucinogens. “People are desperate.” But a pill that people could pop without clinical supervision and without an hours-long ego-dissolving odyssey would, he predicts, be far more popular.

A company Olson co-founded, Delix Therapeutics, has several compounds under development that work like psychedelics without a hallucinogenic effect. He hopes to begin trials as soon as next year.

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In another line of inquiry, Olson, working with Boris Heifets, an assistant professor of anaesthesiology at Stanford University, plans to test this hypothesis in humans by giving psychedelic drugs to participants while they are under anaesthesia.

Olson’s is a minority position among his peers. Matthew Johnson is a psychologist and professor at Johns Hopkins Medicine and a leading researcher in the field. “Obviously I think there’s promise in psychedelic therapy,” he says, “and by psychedelic therapy I mean: high doses, preparation, pay attention to the experience.”

Johnson is working with a company, Mydecine, to bring to market a psilocybin-based anti-smoking product.

There is a flip side to Olson’s argument, too. One of the people who makes it happens to be his collaborator, Heifets, a doctor and neuroscientist. In the big psychedelic trials so far, Heifets points out, the placebo groups also had strong outcomes. In other words, just giving psychedelic-type therapy without the psychedelics does a lot of good.

Rather than domesticating the compounds to fit into our existing healthcare system, the way Olson proposes, perhaps we should try to do something more like the opposite.

“Why do we have a mental health crisis?” he asks. “I don’t think it is because we’re missing the right antidepressant drug.”