Marijuana Business Magazine April 2020

Marijuana Business Magazine | April 2020 82 than smoked cannabis. They’re two different drugs. There’s a change in the cannabinoid profile that’s different between smoked and vaporized. There’re also differences in the terpenes,” Chamberland said. Essentially, if you take one bud, break it in half, smoke one half and vape the other, the cannabinoids, terpenes and amounts they are distributed in will be different in smoke and vapor. Tetra also studied the doses patients could handle without suffering adverse side-effects such as fainting or being too intoxicated to speak. Researchers also found that subjects rapidly developed a tolerance to cannabis and, if they slowly exposed subjects to the drug over five days, they could avert side-effects. “That’s key, because if you’re hitting patients with cancer and palliative care, you don’t want them to stop taking the medication because of adverse events,” Chamberland said. “We were able to show in volunteers that we could eliminate that with a simple titration strategy that we now include in all of our trials.” Tetra Bio-Pharma also discovered, shortly before they planned to submit an Investigational New Drug application (see “Steps for Cannabis Drug Studies”), that the flower they were using had developed mycotoxins during the drying and curing processes. That forced them to shut down the study. “Until we had … a better way of ensuring that the lots were mycotoxin- free, we terminated the project. We also shared that with the FDA, so they were aware that we had done that. We voluntarily sent them all the information on the mycotoxins,” Chamberland said. Rather than abandoning the study altogether, Tetra used the opportunity to tighten its contaminant monitoring protocols. The company also developed new mycotoxin-prevention-and- monitoring strategies, such as sterilizing grow rooms after harvests and using DNA sequencing to identify fungus genes. When Tetra presented this data to the FDA, the agency allowed the trial to be “reactivated,” granting the company an Investigational New Drug application for a Phase 2. “We were transparent; we showed them everything we knew about mycotoxins and how we now control them, and they came back and said you can move forward. That, to me, is really positive,” Chamberland said. “Because we were transparent, we burst the bubble. We said, ‘We discovered this quality problem, here’s how we address it, here’s how we now ensure patients are safe.’ And they said, ‘Go.’ It would have been a great time for them to say, ‘Nope, take a hike.’ But they didn’t. That shows there is an opening from the FDA to bring cannabis smoked drugs to the market.” There are several more steps for Tetra to bring cannabis to the pharmaceuti- cal market, including further studying the composition of cannabis vapor and testing these products against placebos. These tests will be conducted by Dr. Sue Sisley, a pioneering physician research- er based in Arizona. Chamberland is confident that cannabis will easily beat the placebo, because patients—usually sooner rather than later—figure out when they are not high that they are on the placebo. “That creates what we call a bias. And the patients will be reporting more negatively when they realize they’re on the placebo. The FDA and its northern counterpart, Health Canada, know about this bias, but there’s no choice, you have to do that. Morphine, opioids and other drugs went through the same thing,” Chamberland said. He believes the FDA approving cannabis to treat cancer pain is more of a question of when rather than if. “We’ve developed this as any other drug, so when we talk to the FDA (or) Health Canada, we basically need to have data for each regulation they have. We’ve never requested a different path from the classic path for drugs,” Chamberland said. “The next stage is comparing it once and for all in the pivotal trial against placebo. And the next result, if it works, is that it’s there for patients. That, to me, is an amazing achievement for our company … and that would be a major success for the cannabis industry.” As part of its research into cannabis medicine, Tetra Bio-Pharma compared the contents of smoke and vapor delivery methods. Courtesy Photo Research Project