It was just one of many recent breakthroughs in the use of psychedelic drugs to treat mental disorders.
A study published in Nature last July showed that the effects of psilocybin — the psychoactive compound in magic mushrooms — can last for weeks after taking it, offering new hope for those suffering from severe treatment-resistant depression and trauma-related disorders such as post-traumatic stress disorder.
The study adds to a mounting body of evidence showing that psilocybin may promote the growth of nerve connections through the development of new nerve growth and new synaptic connections between them, a phenomenon known as neuroplasticity, says Peter Silverstone, a psychopharmacology expert in the Faculty of Medicine & Dentistry at the University of Alberta.
“This is why psilocybin may help so many individuals overcome the effects of long-term mental health issues — by reversing nerve changes,” he says. “It has the potential to be the most dramatic treatment breakthrough in mental health for decades.”
The potential is so encouraging that Silverstone launched his own Edmonton company called Zylorion Health in 2021.
The therapeutic potential of psychedelic drugs like LSD, psilocybin and MDMA is looking more promising every day, he says. Over the past two decades there has been an explosive renaissance in the appreciation of psychedelic drugs for treating mental disorders such as depression, anxiety, PTSD and addictions.
This renaissance was the subject of Michael Pollan’s 2018 No. 1 New York Times bestseller, How to Change Your Mind, which was made into a Netflix documentary series. In 2022, Silverstone released his own contribution to the field, The Promise of Psychedelics, which made the Wall Street Journal bestseller list.
Reviving an ancient sacrament
The science may only now be catching up, but the promise of psychedelics is hardly new. Magic mushrooms have been used by Indigenous peoples in South and Central America as a sacrament for hundreds of years, and psychoactive substances have been used for spiritual healing around the world for millennia.
The potential of psychedelics first emerged in scientific research in 1938, when the Swiss chemist Albert Hoffman accidentally invented lysergic acid diethylamide (LSD-25) when looking for a drug to stimulate circulation in the body.
Five years later he ingested a tiny amount of the compound and experienced the world’s first “bad trip.” He described feeling like he was losing his mind, and thought he might actually be dying. But the nightmare of a demon seizing his “body, mind and soul” was followed the next day by an afterglow resembling spiritual awakening: “Everything glistened in a fresh light. The world was as if newly created.”
Hoffman was convinced the drug could have revolutionary pharmaceutical applications. For one thing, it opened up questions about how such a minuscule amount of a compound, as little as a quarter of a milligram, could have such a profound effect on the mind. As Pollan points out in How to Change Your Mind, the discovery of LSD helped launch the birth of modern brain science in the 1950s.
The next two decades saw the first wave of research into psychedelics, the best known of which is the LSD program run by Timothy Leary, the Harvard psychologist who famously urged a generation of students to “tune in, turn on, drop out” in the early 1960s. LSD’s association with the 1960s countercultural movement led to its being outlawed in 1968.
Research on psychedelics was banned in 1970 after a number of unfortunate deaths, and mostly driven underground until the publication of a landmark 2006 report in the journal Psychopharmacology. It found that “psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance.” The renaissance had begun.
The Western Canadian connection
Perhaps not as well known is that the modern history of psychedelics is in good measure a Western Canadian story. Humphry Osmond, the British researcher who coined the term “psychedelic” in the 1950s, spent most of his career at the Saskatchewan Mental Hospital in Weyburn, which under his influence became the world’s most important hub for psychedelics research.
According to Pollan, Osmond contributed “more to our understanding of these compounds and their therapeutic potential than any other single researcher” and was famously responsible for providing mescaline to Brave New World author Aldous Huxley, who recounted that experience in his 1953 book, The Doors of Perception.
Almost 70 years later, in 2022, Alberta became the first Canadian jurisdiction to regulate the use of psychedelic drugs. The drugs are still illegal in Canada, but doctors and researchers can seek approval from Health Canada to use them in clinical trials or in therapy.
Silverstone applauded the move at the time, telling CBC that regulation would prevent harm while more research is done to back up the “huge promise,” which was growing at a rapid pace.
Earlier this year, Alberta Blue Cross became the first insurance company in Canada to include psychedelic-assisted therapies in its coverage.
A healthy dose of caution
Health law researcher Timothy Caulfield, known for his skepticism about any therapeutic trend that generates hype without solid evidence, agrees that psychedelics hold enormous promise. But true to form, he recommends taking any exaggerated claims with a grain of salt.
“I’ve said the same thing about precision medicine, microbiome research and stem-cell research — watch the hype. Especially when you have influencers promoting microdosing and all these other approaches where evidence is still emerging on how to do it safely.”
“White Hat” bias can also be a misleading factor in research, he adds, a phenomenon defined as “the distortion of information for what might be perceived as righteous ends.”
“We saw that with COVID research,” says Caulfield. “When there’s this strong desire for this to work, you get an efficacy bias emerging.”
The Federal Drug Administration’s rejection of MDMA — also known as 3,4-methylenedioxymethamphetamine, or more commonly as “molly” or “ecstasy” — for use in therapy last summer was a bracing reminder that delivering on a drug’s promise means getting the research right. The FDA didn’t determine that the MDMA wasn’t safe or effective, only that in a study up for review, the methodology was flawed.
Proceeding with cautious optimism
Having spent his life in the field of psychopharmacology, Silverstone is acutely aware of the dangers psychedelics pose. Despite his enthusiasm for their potential, he is quick to stress that casual or recreational use without carefully guided therapy can turn out badly.
He points to a psychedelic outpatient clinic in Berlin, for example, that helps people overcome bad trips that just won’t end. Though rare, some people become victims of a hallucination persisting perception disorder, a condition that hinders their mental health for months or years after taking a psychedelic substance. Others complain of depersonalization or derealization syndrome, psychosis and anxiety.
“Then you’ve got this pilot for Alaska Airlines who tried to shut off the plane’s engines in mid-flight after taking mushrooms,” says Silverstone. “These things are not risk-free. But the question is, how big is the risk? How do we manage it?”
Under the right supervision, taking the right dose of psychedelics has shown dramatic success where other drugs and treatments have failed, he says.
Silverstone’s own journey in psychopharmacology began as a child growing up in London, England. His father was one of the first professors in the field, writing the standard textbook on the subject.
“I was privy to, and participated in, many discussions on his research in my early teens, so I think I was always primed to follow this career path,” he writes in The Promise of Psychedelics. He entered medical school at 17 and completed nine months as a junior neurosurgeon before training as a psychiatrist.
In his book, he describes his demoralizing first day as a psychiatrist. Every patient he saw was “depressed and suicidal,” he recalls. “They’d all had some treatments which clearly hadn’t worked. Often medication alone doesn’t work, especially for conditions like PTSD, grief or personality issues.
“At the end of my first day, I wondered what I could offer that they hadn’t already tried. It was a shock.” That’s when Silverstone first realized how urgently the world needed new treatments.
Decades later, what excites him most about psychedelics are the recent findings in brain science, especially those demonstrating that psilocybin — far from only causing hallucinatory perceptions — can improve neuroplasticity.
Last summer a study published in Nature demonstrated that psilocin — the compound to which the human body converts psilocybin — and LSD bind to a receptor called BDNF TrkB, accounting for how these drugs might produce neuroplasticity.
“To me, this neuroscience explanation was extraordinarily fascinating,” says Silverstone.
Do good things come in small doses?
The most dramatic and pronounced effects of psychedelics come in high doses, often producing the kind of hallucinatory experiences that can leave a lasting, almost mystical impression.
“Many individuals share that they have gained tremendous insight into things that weren’t clear before,” says Silverstone. “These include spiritual insights, which can be held with deep intensity.”
But the biggest payoff — and research push — for the treatment of mental disorders, he says, could be in the practice of microdosing, or taking frequent doses of about 10 per cent of the amount required for a psychedelic “experience.” Although more research is needed, he says, some studies have shown improvements in anxiety, depression and PTSD.
One study from 2018 showed that, over a year, half of participants reported improved mental health in a wide range of psychiatric conditions. They also reported better results from microdosing with psychedelics than with conventional treatments.
There are more than 800 psychedelic compounds known to science, many of them poorly understood, says Silverstone. But after reviewing more than 350 peer-reviewed scientific articles and publications, he ranks the best-known and most widely used compounds — namely psilocybin, ketamine and MDMA — based on efficacy and safety.
The top contenders
Psilocybin comes out on top, partly because of its promise for microdosing, but also because of the current North American push toward legalization and the research it will galvanize.
“Pure psilocin may not present longer-term risks, and with low-dose use there appears to be a very low risk of addiction … and it may turn out to be helpful in many other psychiatric and neurological conditions,” says Silverstone.
“Humans have been using magic mushrooms for millennia, but in terms of mental health and possibly other neurological conditions, it feels like the promise of psilocin or psilocybin is profound.”
Among the psychedelics, psilocybin also appears to pose the lowest risk to the cardiac system, compared with the psychoactive beverage ayahuasca, for example. But it is unlikely any psychedelic avoids that risk entirely.
“A big review in 2024 found there’s a real risk to microdosing LSD and other psychedelics, and we now know that MDMA definitely causes this problem, especially for chronic users,” he points out.
Silverstone’s “silver medal” goes to ketamine, first invented in the early 1960s as an anesthetic. It has a somewhat alarming reputation since its role in the death of Canadian celebrity and Friends star Matthew Perry, but Silverstone argues that when used carefully under medical supervision, it can be transformational. The former director of the National Institute of Mental Health has called it “the most important breakthrough in antidepressant treatment in decades.”
The downside is that ketamine can be dangerous when used without proper supervision, “causing neurological and cognitive issues, brain damage and even death,” says Silverstone.
Silverstone gives third place to MDMA for its therapeutic potential. It has shown to be effective for treating PTSD, he says, and may turn out to be useful in patients with depression, anxiety, addictions and eating disorders.
But as with many of the psychedelics, the risks of chronic and unsupervised use of MDMA are concerning, including brain injury, neurotoxicity, heart damage, and even sudden cardiac arrest and death.
“This is why it’s most likely that MDMA will become part of a psychedelic-assisted therapy option only for treatment-resistant patients with a few major conditions,” says Silverstone.
Silverstone’s assessment of current psychedelic research comes with a caveat: The field is accelerating so quickly, he says, with discoveries emerging almost every month, that what he wrote even two years ago could already be out of date.
“A prediction I made a year ago could already be wrong, and a prediction I made three months ago might need modification,” he says.
Such intense blossoming of psychedelics research is an encouraging sign. But both Caulfield and Silverstone agree that any promising trend comes with hype, and if something seems too good to be true, it probably isn’t. Panaceas simply don’t exist.
But it is true that we could be on the brink of a new dawn in human mental health, thanks to a substance we’ve known about for thousands of years.