National Post (National Edition)
Could the `spirit molecule' be a treatment option for stroke?
VANCOUVER-BASED COMPANY PUTTING UNIQUE HYPOTHESIS ABOUT HEALING EFFECTS OF PSYCHEDELICS TO THE TEST
About every 10 minutes, someone in Canada has a stroke. Stroke is the leading cause of adult disability in the country and the third leading cause of death, per the Ontario Stroke Network.
The vast majority of strokes are ischemic strokes, which occur when blood flow to the brain is obstructed. Treatment options are limited.
In 1999, Health Canada approved a clot-clearing drug called tissue plasminogen activator, or tPA, to treat ischemic strokes. For tPA to be most effective, it needs to be administered within a few hours of symptom onset.
But tPA can be deadly if it's given to someone who has had a hemorrhagic stroke, meaning patients have to wait for a CT scan before they can receive treatment, a costly delay that can have devastating consequences.
More than 20 years since tPA debuted, it remains the first and only drug approved by the U.S. Food and Drug Administration (FDA) for acute ischemic stroke. Researchers have spent decades and billions of dollars unsuccessfully searching for alternative drugs that can preserve neurons and ideally be given to patients without requiring a scan.
A study published in the Annals of Neurology documented more than a thousand potential neuroprotective drugs that were put to the test from 1957 to 2003, none of which were established as viable treatment options.
Now a Vancouver-based company is looking to change that.
The novel treatment? N, N-Dimethyltryptamine, better known as DMT, a psychedelic compound that is part of the tryptamine family, alongside substances like psilocybin, ketamine and LSD. DMT is also known as “the spirit molecule.”
While DMT can be synthesized in a lab, it occurs naturally in many plant varieties, some of which have been used in religious ceremonies in South America for centuries. DMT is the main active ingredient in ayahuasca.
In February, Algernon Pharmaceuticals announced it was planning to be the first company in the world to test DMT in human clinical trials for stroke. Strokes kill neurons, and for every hour left untreated, ischemic stroke patients can potentially lose about the same amount of neurons as they would across four years of normal aging.
The hope is that the drug will promote neurogenesis and neural plasticity, leading to new synaptic connections, and potentially allowing stroke victims to recover faster and with less damage. It could be administered shortly after a stroke occurs by a continuous intravenous injection at a sub-psychedelic level, meaning patients would not experience hallucinations.
In March, Algernon, which has also filed provisional patents for new forms of DMT, submitted a package to the FDA regarding the design and scope of the company's preclinical and early phase stroke clinical programs.
Earlier this month, Algernon says it received positive feedback from the FDA regarding its planned Phase 1 clinical trial, which is set to begin later this year with the U.K.-based Hammersmith Medicines Research, a company that provides clinical trials for the pharmaceutical industry and is licensed to work with psychedelic drugs.
One of the consultant's on the trial is Dr. David Nutt, a psychiatrist and a neuropsychopharmacology professor at Imperial College London and formerly the U.K. government's top drug adviser.
“The idea is can we stimulate neurogenesis without being psychedelic? And I think that's a really clever idea. No one knows. But if it works, it's very exciting,” Dr. Nutt said.
The idea is clever for a few reasons, he says. It's a novel approach and because the drug will be administered intravenously, at sub-psychedelic levels, there is flexibility with the dosing and the duration of action.
“How you keep it a sub-psychedelic dose is going to be challenging, and we've got some ideas about that, but also if people are conscious, they can talk to you. If they start to say `I don't like the side effects I'm seeing, I'm thinking funny thoughts,' you can just turn it off and literally within a minute the effect dissipates.”
Phase 1 of the trials will seek to establish dosages and the safety of the treatment, while the next phase will focus on recovery and rehabilitation.
The company will look to build upon a foundation of preclinical studies that have shown DMT can promote neuroplasticity.
A study published last year in the journal Experimental Neurology demonstrated the neuroprotective effect of DMT in an animal model. After blood flow to the brain was restricted in rats, those treated with DMT had fewer lesions on the brain and recovered faster and with less severe effects.
Algernon hopes that its microdosing approach may encourage a wider review and acceptance of the therapeutic potential of DMT and open the doors for further research.
Testing psychedelic drugs is not easy, Dr. Nutt says.
“The barriers are still immense. But we're hoping that the more research is done and the more clinical utility is demonstrated that the barriers begin to come down. At present they're enormous and they add vast costs but also time. Getting import-export licenses for these drugs is a pain in the butt. It can take months to get permission to move the source compound across to another country to do the testing.”
Algernon believes its approach could potentially lead to a Breakthrough Therapy Designation from the FDA, which enables priority review and can fast-track the clinical trial process. In 2017, the Multidisciplinary Association for Psychedelic Studies (MAPS) received the same designation for its approach in treating post-traumatic stress disorder with MDMA.
But for real progress to occur, these types of substances need to be rescheduled, says Dr. Nutt. He was famously fired from his position with the U.K. government a little more than a decade ago after stating substances like alcohol and tobacco were far more harmful, both to the individual user and society at large, than LSD, ecstasy or cannabis.
“If the schedules don't change, they're not going to be medicines, that's a fact,” he says, adding that the only thing that can motivate that change is medical data.
These days, Dr. Nutt is still teaching and conducting research at Imperial College and is involved in a number of trials with psychedelic medicines, including psilocybin for the treatment of obsessive-compulsive disorder, anorexia, and chronic pain.
“Before I was sacked, no scientists in Britain would actually tell the truth about drugs, they didn't ever want to confront the fact that the biggest killer in Britain is alcohol. And after I was sacked everyone said, `Of course it is. It's obvious. So why do we care about these psychedelics that aren't very harmful at all?' So the public completely swung around to us. The fact that Oregon is now legalizing mushrooms, against federal law, against the UN Convention, tells us we won the argument in the public. But we've still got to win it with the politicians.”
Having turned 70 years old last month, Dr. Nutt says “he's hanging on to see sanity eventually prevail over the drug policy.”
He adds that, at the moment, psychedelic research is a good field to be in, which is a big change from a decade ago.
“It is buzzing at present and I think that even if only half of the hope comes to fruition is still going to be a hell of an event,” he says. “I hope I live long enough to see it all sorted.”