There is a magical moment in the pharmaceutical industry when a government approves a new treatment. For companies researching psilocybin, the psychoactive component in psychedelic mushrooms, that moment is now.
Late last year, the United States Food and Drug Administration (FDA) designated psilocybin as a “Breakthrough Therapy,” a label that fast tracks clinical trials. The move only comes when there is significant evidence that a new treatment might prove far more effective than current treatments.
In the case of psilocybin, it’s drug-assisted therapy for Major Depressive Disorder (MDD). So far, in clinical trials, the results of psilocybin-assisted therapy have outstripped those of early trials of antidepressants.
Like breath strips, but with psilocybin
Cybin Corporation, one of many companies pursing psilocybin treatments, is throwing another factor into its clinical trials: drug delivery method. Existing research has focused on oral treatments, or pills, but Cybin is conducting trials with dissolvable films remarkably similar to minty breath strips. Cybin has partnered with pharmaceutical manufacturer IntelGenx to make the films, which may end up with a cherry flavor.
IntelGenx’s sublingual films can deliver a pharmaceutical ingredient directly into the bloodstream when placed under the tongue, as opposed to the long path through the gastrointestinal system and the liver when a pill is swallowed. With other pharmaceuticals, medication films have been shown to kick in faster and pack a harder punch with a lower dose.
In theory, the same will hold for psilocybin, and Cybin hopes to deliver 25 milligram (mg) results with a much smaller amount.
A 25mg psilocybin pill has become the unofficial standard for a therapeutic dose in clinical research and has been shown to be effective in treating Major Depressive Disorder (MDD) in trials.
Cybin is embarking on a clinical trial to determine how many milligrams on a dissolvable film will match a 25-milligram therapeutic dose: one, three, five, or seven milligrams.
“I suspect that the three-milligram dose will be the efficacious dose,” said Dr. Jukka Karjalainen, Cybin’s Chief Medical Officer. But rigorous testing and research is still necessary.
Sublingual vs. ingesting
Pharmaceutical trials follow a marked path. Safety first. Safety and effectiveness second. Safety and effectiveness for everyone third. These are the most basic tenants of the three phases of human clinical trials.
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Cybin’s Phase 2A clinical trials will test the different dosages on the films. Its Phase 2B trial will test the selected film dose against a placebo film on 120 participants who have Major Depressive Disorder, according to the company. Both trials will take place in Jamaica, where psilocybin is legal and Cybin is able to get approval for both studies.
To be clear, this is not microdosing, which is a small amount that is swallowed. Those three milligrams of psilocybin will go directly into the bloodstream from under the tongue and on to the brain. That’s why films can carry a significantly lower dose.
A traditional pill is ingested and travels through the gastrointestinal system and is processed by the liver, explained Dr. Karjalainen. It’s difficult to tell exactly how much of the dose is actually processed, but 50-60% of that 25mg dose could be lost, he said. The percentage that’s absorbed is the bioavailable dose.
“With the oral film dosing, bioavailability goes to 100%,” said Dr. Karjalainen. “The dose that is being given is the dose available to the clinical effect.”
And the dosing of these films is extremely precise.
How are the strips made?
Cybin and their manufacturer IntelGenx purchase biosynthetic psilocybin from a company in the United Kingdom. Psilocybin research is legal in the US and Canada, as long as you get government approval, but producing psilocybin isn’t. Like pharmaceutical cannabinoids, it is produced in labs using different types of viruses and fungi such as yeast.
IntelGenx mixes the imported psilocybin into a solution that then, in many calculated and machined steps, is applied to a liner, explained Horst Zerbe, CEO of IntelGenx. That liner is then carefully cut into narrow rolls, transferred to packing material, further diced into the right size, and sealed into individual pouches—at a speed of 900 pouches per minute.
The time it takes for the psilocybin in the films to kick in isn’t known yet, but IntelGenx has seen significant differences in dose timing in other medications, said Zerbe. For a medication for anxiety attacks, the onset of the film was one to two minutes, compared to a 30-minute onset when that medication was in a pill.
But unlike an anxiety attack, a therapeutic psilocybin session is a trip you carefully prepare for. Traveling from one state of consciousness to another might not be something you want to do quickly. And a departure from traditional delivery methods could mean a departure from expected results.
“I actually think that one of the interesting things about psilocybin is that it is ingested,” said Dr. Alan Davis, an Adjunct Assistant Professor in the Psychedelic Research Unit at Johns Hopkins University who just completed a clinical trial on psilocybin-assisted therapy for Major Depressive Disorder.
“There’s also some question about the importance of the gut in the disruption of mental health processes,” said Dr. Davis. New studies are coming out showing connections between the microbiome in the gut and mental health, he explained, and there are a lot of serotonin transporters in the gut. “It’ll be curious to see,” he added.