Wild Ideas

From battling the next antibiotic-resistant superbug to stemming the opioid epidemic, scientists are looking to nature for the future of medicine

ROSEMARY WESTWOOD
BENOIT PAILLÉ

Consider the elmleaf blackberry from Italy. Or a twiggy bush sprouting beads of blood-red berries, called the peppertree, native to Brazil. Observe psilocybin mushrooms, which sent trip-seekers flocking to Oaxaca in the 1950s; the narrow-fingered cannabis plant, native to Central Asia; the ayahuasca vine, ropey and muscular and now commercially grown in Peru; and the deadly ergot fungus, ancestor of LSD, which grew on the stalks of rye in Medieval Europe.

In the future, when you are sick or sad or depressed, dealing with addiction, suffering from PTSD, or just trying to have a better day, you might turn, as you may right now, to a pill. The difference will be what’s inside it.

The medical world is increasingly looking to nature for the next wave of revolutionary drugs. It’s a moment accelerated by technological advances in neuroscience and biotechnology, by the renaissance of psychedelics, and by sheer necessity, as antibiotic-resistant superbugs conquer hospitals and the opioid epidemic decimates communities. The question isn’t if these drugs will change our societies. It’s how, and how quickly.

MONKEY BUSINESS

In the early 2010s, HIV researchers in the U.S. decided to experiment with cannabis. They had long known illicit drug use was associated with poorer health in those diagnosed with the disease, and they wanted to test the impact of pot. They gave infected rhesus monkeys daily high doses of tetrahydrocannabinol, or THC, the plant’s psychoactive component. The results were startling. Monkeys that received THC were healthier than those that didn’t.

M-J Milloy, a professor and infectious disease epidemiologist in the Department of Medicine at the University of British Columbia, read the study with surprise. Milloy decided to find out whether what worked for the rhesus monkeys would work for people. He’s part of a team that has been conducting a long-running study of about 1,000 people in Vancouver living with HIV, about 90 per cent of whom have at some point used injection drugs. Milloy and his colleagues analyzed data they’d collected, and there it was.

“I’ll never forget the surprise when I finished doing the analysis and saw that, holy shit — pardon me — the folks in this study who are using cannabis have less HIV in their blood than the people who aren’t using cannabis,” he says, “and the only explanation for that has something to do with cannabis.” Pot, it seemed, could somehow help fight HIV.

Milloy calls the moment “eye-opening.” He’s still trying to figure out exactly why cannabis has this effect, and it’s just one of the questions researchers have for how canna- bis might be used for an unknown number of diseases and ailments. A veritable explosion of clinical research is investigating thousands of years of anecdotal experiences with pot — as a sleep aid, anti-anxiety aid and an appetite enhancer. Legalization may have thrown open the doors for use, but we still have far more questions than answers about exactly how cannabis affects the brain, in ways both good and bad.

Even some basic questions remain — like why cannabis might give some people anxiety, what the long-term effects of adolescent use might be or whether it matters how you ingest it. Milloy calls the central issue of delineating between the effects of CBD vs THC the “$64,000 question.”

In their latest published research, Milloy’s team took data from the Canadian National Health Survey and found people diagnosed with PTSD who used cannabis did not have a risk of suicidality or depression — two very common symptoms of PTSD. It could have something to do with cannabis’s ability as a sleep aid, Milloy posits, a theory he’d like to test in a clinical trial he hopes to launch in the New Year.

Meanwhile, specialized cannabis-derived drugs are hitting the market. The United Kingdom’s National Health Service (NHS) approved that country’s first cannabis drugs in November 2019. One uses THC and CBD, or cannabidiol, to reduce stiffness and spasms for people with multiple sclerosis, and another designed a drug to reduce seizures for people with epilepsy containing CBD. American regulators approved a cannabis drug for epilepsy in 2018, and another U.S. study underway will look at cannabis’s impact on stress and anxiety. In research bound to interest women the world over, one Harvard psychiatrist and cannabis researcher is planning to examine the use of CBD suppositories for PMS symptoms and cannabis’s impact on menopause.

One of the most urgent areas of cannabis research is figuring out how the drug might help people who are addicted to opioids and at risk of overdosing amid the fentanyl crisis. A study based in New York published in May found that opioid users who were given CBD pills had significantly reduced opioid cravings and anxiety. One of Milloy’s studies of the group of people living with HIV in Vancouver found that those with THC in their urine were far less likely to have fentanyl in their urine, a telling correlation. Milloy says he’s heard of groups in Vancouver’s Downtown Eastside that have started to distribute free cannabis, convinced that it can save lives. And that’s not far off from a research project Milloy’s team has planned.

“One of the trials we’re thinking of would be to recruit a bunch of people at risk of overdose, allow them access to a free source of legal, regulated cannabis, and see what happens,” he says.

Legalization may have thrown open the doors for use, but we still have far more questions than answers about exactly how cannabis affects the brain, in ways both good and bad.

TRIP OR TREAT?

Just a few years after Michael Pollan, the bestselling journalist, published “The Trip Treatment” in the New Yorker, the psychedelic drug exposé that mainstreamed the new wave of psychedelic research, the University of Toronto is hoping to launch what researchers believe is the first rigorous, double-blind clinical trial of microdosing. 

Microdosing, trending among Silicon Valley-types for years, is believed to give its users a productivity hit. In survey research from the University’s new Psychedelic Studies Research Program, microdosers said their tiny doses of LSD (lysergic acid diethylamide) or psilocybin (the magic in magic mushrooms) put them in a calmer, better mood. They could focus more easily and get along with their families, something Norman Farb dubbed the “Family Feud effect.”

Farb is an assistant professor of psychology and the director of the new program in Toronto, where he works with two graduate students. Within the next year, they would like to recruit 100 people to test the efficiency of microdosing psilocybin. The Aztecs may have called it “God’s flesh,” but Farb says there’s no evidence proving that microdosing (which the department defines as 0.2 grams of dried mushrooms) works any better than a placebo. The team has applied for an exemption from Health Canada to study the drug, which Farb hopes to have by the summer of 2020.

[Psychedelics] could build within us a deeper sense of connection to nature and the environment, just when the world’s masses are threatening the planet’s very future with our gluttonous consumption of fossil fuels and destruction of habitats.

The research follows a series of dramatic advances in the neuroscience of full-dose psychedelic use, some of it — including LSD and psilocybin, derived from the natural world and others made synthetically, including MDMA — part of clinical trials as a possible treatment for PTSD, and ketamine, a component of a new FDA-approved drug for depression. Imperial College London and Johns Hopkins University in Baltimore have launched the world’s first centres for psychedelic research in the past year, aptly named The Center for Psychedelic and Consciousness Research. In brain scans, scientists have shown that psychedelics produce diverse and unpredictable neural activity. One study found psilocybin use could allow us to manufacture a near-death experience. It may even shift us politically away from authoritarianism. And it could build within us a deeper sense of connection to nature and the environment, just when the world’s masses are threatening the planet’s very future with our gluttonous consumption of fossil fuels and destruction of habitats.

Some senior officials at the University of Toronto have confessed to Farb that, as children of the 1960s, they’ve been “waiting a long time for this,” Farb says. That first mid-century revolution of psychedelic research included the unlikely town of Weyburn, Saskatchewan, where Humphry Osmond and Abram Hoffer experimented using psychedelics to treat alcoholism and schizophrenia (Osmond coined the term “psychedelic”). The drugs’ recreational popularity defined the era, though in private, research using LSD included the CIA’s search for mind control, when it conducted experiments that tortured and killed prisoners. Timothy Leary remains the epitome of the evangelizing psychedelic scientist of the time; the Harvard researcher left academia to form a kind of psychedelic religion that Erika Dyck, author of Psychedelic Psychiatry: LSD from Clinic to Campus, has dubbed “inner peace through hallucinogens.”

The study of these drugs still remains risky, Farb says, plagued by skepticism and uncertainty for researchers. He’s hoping to establish not just one reputable study, but a framework for a future of rigorous psychedelic research. Farb’s background is in studying meditation — another field deemed unserious until it exploded into the mainstream and researchers began to find evidence that it works. If meditation can be proven to help people, he wondered, then why not see if that’s true for psychedelics? Even those convinced that these drugs are dangerous should want the science to back that up, he argues.

“If you think this is a pernicious, really risky, bad thing to do, you would want a publicly accountable, transparent research project to demonstrate those dangers,” Farb says. “If you think that this is going to free the world and transform human consciousness, then you would still want very rigorous, unbiased research to demonstrate those benefits.”

Strangers are quite literally hounding Farb to get into the study, despite the fact that the team is waiting for Health Canada’s sign-off before beginning to recruit patients (so no, do not read this and email him). The research could not only establish whether microdosing actually gives you an edge, but if it’s safe. Should you, for instance, go pick your kids up from school while on psilocybin?

“No one would think it would be okay to drive a car on a full-dose trip, but they would on microdosing,” Farb says.

He’s also worried about the corporatization of the re- search by venture capitalists who smell fortunes in the new frontier of psychedelics. His team has been approached by people keen to fund their research, but who also want to “own the safety data,” he says.

“Corporations and venture capitalists were contacting us trying to figure out how they can sort of use us to help develop intellectual property, and we’re like, if no one starts getting into this playground, you know, the private sector is going to push this into the public,” he says. “And there will be no conflict-free data on whether this is really good for people or not.”

Brian Rush, a long-time mental health researcher at the Centre for Addiction and Mental Health in Toronto has seen the same interest at conferences he’s attended of late. “We’ve had venture capitalists coming in asking questions like, ‘What are the profit margins for this medication? Who is this going to work on? If it’s like, one pill and you’re cured, who’s going to make any money on that?’” he says. Private funding will of course be needed to establish research and manufacture drugs, Rush says, but “we need to be very careful about the role of this kind of partnership between public and private.”

If meditation can be proven to help people, [Farb] wondered, then why not see if that’s true for psychedelics?

FROM EATING DISORDERS TO ENLIGHTENMENT

For seven years, Rush has been investigating the possibilities of another psychedelic: Ayahuasca. He’s part of a team studying its effects at a treatment centre in the Peruvian Amazon called Takiwasi. During the course of a nine-month program, ayahuasca — a brew of the ayahuasca vine and chacruna leaves, which contain the hallucinogen DMT — is administered in group settings, along with other psycho- therapy treatments. Rush says they hope to begin analyzing data collected from participants (in some cases as long as two years after treatment) this year. “We have crossed the threshold of acceptability” for studying psychedelics, Rush says. “I’m not the only one coming out of the closet.”

Like other psychedelics, ayahuasca is believed to act on networks in the brain associated with depression, sub- stance abuse, and anxiety disorders. Studies indicate it could help people fight alcoholism and depression. A Laurentian University researcher found it might benefit people with eating disorders. It could also have a psychiatric ability to loosen memories and free up repressed emotions, Rush says. And it is, even more than other psychedelics, he adds, associated with acute religious experiences of God. One study found users of ayahuasca were more likely than users of other psychedelics to commune with a higher power on the drug. “I think the job of researchers now is to try to go slow,” Rush says. “Not make some of the mistakes that were maybe made in the 1960s.”

Even if these drugs reach the public, there’s no clear picture of who will be able to use them, and how. “What is this go- ing to cost? Are we creating a medication, or a therapy only for the rich? I hope not. Are we creating a system that is only available to people with health insurance? I don’t know,” Rush says. Ayahuasca in particular has one key side effect that could dampen pharmaceutical interest: The end result isn’t only a cosmic high, but puking.

“Many people coming to experience this as part of the healing process, part of a cleansing,” he says. “I’m not sure the pharmaceutical companies will want to go that far.”

Like other psychedelics, ayahuasca is believed to act on networks in the brain associated with depression, substance abuse, and anxiety disorders. Studies indicate it could help people fight alcoholism and depression.

THE SUPERBUG SOLUTION

In November, the Canadian and U.S. governments issued apocryphal warnings about the future of antibiotic resistance. The Public Health Agency of Canada estimated up to 40,000 Canadians could die by 2050 from a drug-resistant infection, and potentially 300 million globally, calling its own estimates “alarming;” the U.S. Centers for Disease Control and Prevention found the threat is greater than earlier estimates had suggested, and that one American dies of a drug-resistant infection every 15 minutes.

Candida auris is one such superbug swarming hospitals and confounding efforts to kill it. Cassandra Quave, a medical ethnobotanist at Emory University in Atlanta, Georgia, believes she has identified a compound that could cripple the bacteria’s power. The finding is one of a series of discoveries Quave’s team has made by studying the original source of medicine: plants.

Plants, as Quave puts it, “can’t just get up and move.” To defend themselves against attacks or attract pollinators and seed dispursers, they “rely on this very intricate system of chemical signaling into the environment, and each plant tissue produces very unique and specific chemical signals to achieve those ends,” Quave says.

By harnessing those mechanisms, Quave believes a whole new range of drugs can be created not just to mimic the way antibiotics kill bacteria, but to discover a plethora of other ways to make bacteria less effective, and therefore kneecap its ability to kill us — plant chemicals, for instance, can stop bacteria from releasing the toxins that break down human tissue and inhibit their ability to share genes and evolve immunity.

“We’re entering into a period known as the post-antibi- otic era,” she says, a combination of the overuse of existing antibiotics and the lack of effective new options. Antibiotics only really revolutionized medicine in the last 100 years with the discovery of penicillin. Quave and others, like Harvard ethnobotanist John de la Perra, believe that technological advances — such as analytical chemistry instruments like mass spectrometry — offer a way to understand the complex molecular networks of plants and unleash their power. As a result, ethnobotany, the study of traditional plant knowledge, could become the new frontier of drug discovery.

For years, Quave and her colleagues have been travelling the world to learn from indigenous healers and scouring old texts for insights (one recent study examined the Con- federate Army’s field guide for medicinal plant use during the Civil War). Her work both searches for chemicals that could be used in new medical devices or drugs and tries to establish data to determine which ancient practices work (ethno- botanists work within ethical frameworks designed to ensure the communities they visit reap the benefits of the research they aid, exemplified by the Nagoya Protocol).

Quave’s study of the Brazilian peppertree has revealed another chemical that seems to protect against a nasty staph bacteria.

Quave’s lab has developed a bandage to heal stubborn wounds by using an extract from the elmsworth blackberry grown in Italy. They’re working on developing plant-derived drugs to fight melanoma.

Their study of the Brazilian peppertree has revealed another chemical that seems to protect against a nasty staph bacteria. The plant is currently considered an invasive pest in Florida, where scientists recently released thousands of tiny insects called thrips as a biocontrol to stem its spread. “The irony of this for me is, wait, instead of getting rid of it, maybe we could use this as a medicine,” Quave says.

The Royal Botanical Gardens, Kew, in the U.K. estimates there are about 391,000 plant species in the world — one in five of which are at risk of extinction. Quave says about 28,000 have been used in medicine in some way, and yet Western medicine has only studied a few hundred of those in real depth. The possibilities are a whole other kind of mind-bending. “There are,” Quave says, “literally tens of thousands of plants to be investigated.”

Sorry, you’re not quite old enough to know if Jonathan Adler designs dirty but lives clean.

But we will be here waiting for you.

In this light it’s hard
 to tell how old you are,
 can we ask your age flattering isn’t it?

Are you of legal age in your province?