[MUSIC] Okay, so we're going to talk in this lecture about barriers to research. And why we don't know more than we know now about the effects of cannabis, especially in terms of the potential benefits. I like to use this slide here as a sort of quick introduction to the hurdles, the barriers that we faced over the last five or six years. And what you see here is a person, that would be me about five years ago, contemplating this notion of how do we go about doing cannabis research. And of course, finding a barrier between what we want to do and where we're at now. So three of the barriers we'll talk about are the FDA, the DEA, and NIH. And so the first couple of years basically was trying to figure out ways, or can we dig under the FDA barrier? Can we climb over a barrier, is there some way to blow up a barrier? It was a difficult process, so why, where do these barriers come from, why is it difficult? So the beginning of this goes back to 1970 with the Controlled Substances Act. And we talked a little bit about the history in the last module in terms of treaties and the legal system, and what led to that. But in any case, the big one here is the Controlled Substances Act of 1970. And you see Richard Nixon over here signing the Controlled Substances Act. That controls the manufacture, importation, possession, use, and distribution of cannabis and other drugs. And basically puts these on the schedule from I to V, with schedule I being the most restrictive. Schedule I basically means there's a high potential for abuse, no accepted medical use, lack of safety even when medically supervised, so imagine that, right? Cannabis has been on schedule I, still is today, since 1970. And what schedule I means is that cannabis isn't safe. Even if you're sitting in front of a doctor, right, it's still not safe. [LAUGH] It's still not safe to use cannabis. Other drugs, LSD, heroin, for example, also on schedule I. Okay, so this is just a nice little graphic that shows you the different schedules. Provides you a description of each schedule, and it gives you examples of what's on the schedule. So you see up here, schedule 1, we have heroin, we have LSD, we have cannabis, Ecstasy. On schedule 2, a bunch of opioids, we have Adderall, Ritalin. And this is ironic, right, fentanyl on schedule 2. Fentanyl, which causes, as you'll see in our opioid epidemic module, a countless number of deaths, right, schedule 2. Anyway, those are the schedules. Now recently with the change in the law, CBD is now on schedule 5. And I should note here too, as long as we're here, right, what is schedule 5? As you know, cannabidiol has almost zero side effects, negative effects. And so schedule 5 is basically reserved for drugs with lower potential for abuse than schedule 4. So it still has the potential for abuse, and consists of preparations containing limited quantities of certain narcotics. Schedule 5 drugs are generally used for these purposes they have here. So bottom line is, even with CBD, it's still schedule 5. Suggesting that people still think it has some potential for abuse, which is pretty ridiculous. Okay, so CBD is schedule 1, not schedule 5, I just talked about that. The FDA recently approved CBD from GW Pharma only. And so the only version or the main version is CBD from GW Pharma now as schedule V. And as I just mentioned, it means it still has a low potential for abuse, but it doesn't have a medical indication. So again, it's not entirely clear to me why it's still on the schedule, but it is. And it definitely, and I know here, defies logic and common sense. And I think this is one the big problems they had for the last 50 years since the Controlled Substances Act. Is that when you have situations that completely defy common sense, when the public out there is like, what the hell, right, like, how does it make any sense? Basically what it does is it diminishes how much people trust federal agencies, right? Because it's pretty clear that these federal agencies are not. Somebody's not being an honest broker in terms of the science and the research and the information, and that's really a shame. All right, so other laws that are important here. The Drug Free Federal Workplace Act passed in 1988. The idea here was they were going to help employers enforce regulations related to drug use. And so what this law says is that any organization that receives $100,000 in a contract or grant of any size must do the following. They must prepare and distribute a formal drug-free workplace policy statement. They must establish a drug-free awareness program. They must ensure that all employees working on the federal contract understand their personal reporting obligations. They must notify the federal contracting agency of any covered violation. They must take direct action against an employee convicted of a workplace drug violation. And the penalty for violation, so as a company, if you don't do these things above, basically, you lose your federal money. There's also the Drug Free Schools and Communities Act. And this law basically says institutions receiving federal funds must establish drug and alcohol abuse prevention programs. They must produce biennial reports on drug and alcohol infractions. It must establish drug use prevention programs on campus. They must certify compliance to the Department of Education. The penalty for non-compliance is that federal funds are taken away. Now, you can imagine that as somebody who works at a university, right, the university basically has to comply with both of those laws. They have to comply with the Drug Free Federal Workplace Act because we have federal grants. They have to, obviously, comply with the Drug Free Schools Act. And we'll circle back to that in a minute in terms of what that means. Now, there are other barriers, not just the laws. These are institutional barriers now that we're going to talk about. So one of the is the Drug Enforcement Agency, or DEA. The job of the DEA is to enforce the Controlled Substances Act and related laws. [COUGH] To do research on cannabis, so there is some wiggle room in the law to actually do some research on cannabis. But to do it, consistent with federal law, you have to get a schedule I license from the DEA. That means you complete a big application. You pass a DEA initial site inspection, which means you have to have a steel safe inside of a locked room inside of a locked building. That's where your cannabis goes, and you have to pass periodic inspections. This whole process takes a long time, although it varies from field office to field office. I personally have done this in the past. Back in 2007, we did some work looking at the acute effects of cannabis using the cannabis grown by the federal authorities, which was a pretty unique situation. Where after doing all this work to get your schedule and license, basically you end up with a FedEx box with a bunch of pre-rolled marijuana cigarettes. Which just shows up in your mailbox, pretty crazy. And anyway, the whole thing was not easy. And there were other reasons that made it less than ideal, and so we have not done that again. So in terms of other barriers, in terms institutional barriers, the FDA, or Food and Drug Administration, along with the DEA, they're responsible for scheduling drugs. The FDA also approves research protocols for schedule I license. So when you do your paperwork for that schedule I license, not only do you get reviewed by the DEA. You also get reviewed by the FDA and NIH. So the FDA is responsible for overseeing clinical research more broadly on drugs. And it's important to note here that a university IRB, or institutional review board, will not allow clinical research to move forward unless the FDA approves it. So you can see right away there's a potential problem here. Even if the university were to allow us to do research on campus with cannabis, it would have to be, if it was clinical, it would have to be approved by the FDA. But since cannabis is not legal, obviously, at the federal level, the FDA will not approve it, so again another big barrier there. So the FDA will only approve cannabis research if you are using federally supplied cannabis. Okay, so what about the last one here, the National Institutes of Health? Some of you may know this, some of you may not. The NIH is the biggest funding agency for health related research. It's actually a collection of different institutes. And they awarded about 39 billion to scientists in 2019 for research. Until recently, it was primarily the National Institute of Drug Abuse that studied or funded work on cannabis. And until recently, it was mostly about the harms. I have to say, NIDA has been fantastic in the last few years about funding both research on the potential benefits, as well as the harms. Their budget, however, is just about 1.1 billion. So kind of a smallish fraction of the overall 39 billion. So the point here is that without funding, it's really difficult to do high-quality research, especially high-quality clinical research. And so you would think, and this is happening to some degree, that with spreading legalization, other institutes within NIH are becoming more and more interested in funding research on cannabis. And as you'll see in this course, cannabis is. I mean, a lot of cancer patients are using cannabis, right? So clearly, an institute that's focused on cancer should be interested in funding research on what is going on with cancer patients and cannabis. Same with aging, the fastest-growing demographic in terms of cannabis use is the over-65 demographic. And then NIDDK, right, we have a whole module on obesity and type 2 diabetes. Because that also is, and has been, a national epidemic. So what is going to be the impact of legalization on obesity and type 2 diabetes? That's a very important area of research. However, I will say this is one institute that has basically shown zero interest in funding any of this research. In fact, we had a grant that was scored pretty much perfectly, and they refused to fund it. So again, we're talking about barriers. And institutes that are uninterested in the effects of cannabis on health end up being barriers to research. Other institutes that have shown interest, NHLBI, NCCIH. They're actually funding work in this area. So for the most part, these barriers have fallen. But there are a few holdouts, and hopefully that will change soon. Okay, so yeah, one more thing to point out here. The University Legal Counsel, and the bottom line here is that we have gotten amazing support from our University Counsel. However, it's still a barrier to research. And let me just sort of explain for a minute how that works. So originally, back in 2013 when Colorado passed their recreational use legalization, we thought, this is going to be pretty easy now to do research. We've done a lot of alcohol research, we've done tobacco research. Surely, it'll be the same thing, we'll just have the same approach. And right away, we were shot down by the legal counsel. And there's a good reason for that, so this is true for all universities. Because of the Drug Free Schools Act and the Drug Free Workplace Act, the university has to basically tell the federal government that we are in compliance with those acts. And the university counsel's position is, if we're doing research on campus with cannabis, then we're not in compliance. And if you're not in compliance, you risk losing your federal funds. At the University of Colorado, that is basically $400 million. And so what legal counsel is going to allow one faculty member to put at risk $400 million? Of course, nobody is, and that's true for every university. Having said that, again, they clearly understand the public health importance. And they have worked very closely with us to find ways to get this research done, and for that I am very grateful. Okay, moving on, so those are the barriers that are in place for now for quite some time. I think it's always important to talk about. Let's not get mired down in the past in terms of these arguments. About how ridiculous it is that you can't do research on something that's being used by a large portion of the population in the state. It just doesn't help to argue those points. I think it is useful to think about the future. And what will the barriers be, say, after the federal government takes cannabis off the schedule, right? And I talk about this some in my presentations across the country. And there is an issue here, and we're going to talk about this a lot more at the end, in the last module, about the future of cannabis research. But in many ways, cannabis does not fit the Western sort of definition of medicine. Again, we'll go into details about that. But the point here is that there may be other barriers that emerge in terms of the FDA and so forth, even when it is off the schedule. And the way people are looking at this now in terms of the FDA is that as long as big pharma's making the product from cannabis and doing the studies, that that's fine. That they will approve those products, but not necessarily approve research or this clinical use of other products that are available on state-regulated markets. And part of their argument there is that the products that are out there in state-regulated markets are not purified to the extent that they are with big pharma. So for example, a hemp-derived version of CBD will have other terpenes and other compounds. And the thinking is that, at least what I hear sometimes from these people, is that we just don't know what's in those products, right? I hear that a lot, we just don't know what's in those products. [COUGH] Well, we could, for example, if you'd let us do the research. But also, we do note, I didn't think to enlarge this. It's not that hard to figure out what's in a product, right? And there's also no research to suggest that CBD that's in a hemp-derived full-spectrum product works any differently than a CBD in a purified product from GW Pharma. And it's also fascinating too here because it's a bit of a double standard. When we talk about the potential for harm with THC, we have now more than 50 years of research on the harmful effects of THC. Based on the notion that THC is THC, regardless of terpenes or other cannabinoids. So for example, lots of animal studies use CB1 agonists that are not THC. Because animals won't self-administer THC, right? And people accept that pretty much as evidence in terms of the negative effects of THC, right? So I think there's a bit of a double standard there. All right, so to summarize, the Nixon administration did an amazing job of raising barriers that persist all the way through today. This comes from the Controlled Substances Act. But also the other acts I mentioned, in the 1980's, that built those barriers even higher. We also have institutions that have their hands tied by those barriers, the FDA, for example. And also their hands are tied somewhat by the sort of rubrics that they use to evaluate medicine and the definition of what medicine is. NIH is definitely getting a lot better in terms of funding work on the public health significance of cannabis. And in particular, NIDA has been fantastic. And although still some work needs to be done, there are some institutes that are still sort of mired in the past. And then finally, it is really impossible for universities to meet the public need for research on the health effects of cannabis. Because their hands are hacked, basically also tied, right? It's you can't put $400 million at risk. These things need to change, people, I mean, this is an obvious thing. Everybody recognizes the need for change. It just seems to be very difficult to get it done.
