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Marijuana, which has been around for over 2700 years, is said to alleviate all kinds of problems — nausea associated with chemotherapy, pain, insomnia, anxiety, depression, dementia, the symptoms of Parkinson’s disease and other neurological disorders. It may even stop the spread of cancer, but this hasn’t been proven conclusively.

In this week’s WhoWhatWhy podcast, Dr. David Casarett of the University of Pennsylvania Medical School talks about its medical value, how we can measure dosing and blood levels, as well as the role of the medical community and government.

He assures us that marijuana overdoses are not fatal and that, given the current efforts toward legalization, we all need to learn more.





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Jeff Schechtman: Welcome to Radio WhoWhatWhy. I’m Jeff Schechtman.

Drive around San Francisco or Los Angeles or New York or any major city today and the green crosses are everywhere. Medical marijuana clinics have proliferated beyond even the number of Starbucks in some cities. But does marijuana really have medical value or is it just a ruse to usher in legalized and recreational use as in Colorado and Washington and soon California? After all, doctors dispensing prescriptions via Skype and dingy clinics doesn’t seem particularly medicalized. However, there may be a real value in marijuana beyond just its known use and value to cancer patients. I’m joined by Dr. David Casarett to look at this issue. Dr. David Casarett is a researcher and professor at the University of Pennsylvania’s Perelman School of Medicine. His studies have resulted in more than a hundred articles and book chapters. It is my pleasure to welcome Dr. David Casarett to Radio WhoWhatWhy. David, thanks so much for joining us.

Dr. David Casarett: Thank you, great to be with you here.

Jeff Schechtman: It’s great to have you here. When did we first identify marijuana as in fact having properties that could have real medical use?

Dr. David Casarett: Well, it’s hard to tell for sure. One way to start that clock ticking was probably 2700 years ago; that’s when the oldest available evidence of cultivated marijuana dates to. An archaeologic find in the Gobi Desert of China show that almost three millennia ago people were cultivating and harvesting marijuana. Nobody knows whether that was for medical purposes or just for fun. A lot of the more recent research, if you can call it that, comes from the 19th century in Calcutta, in India where William O’Shaughnessy was a physician and a researcher, began experimenting with a variety of elements ranging from dementia to hydrophobia or rabies, tetanus and other neurologic conditions. A lot of those experiments were really pretty wild but he was one of the first people, if not the first to begin putting at least some of the principles of science behind medical marijuana’s evaluation.

Jeff Schechtman: And when did we begin using it and seeing its value for cancer patients, particularly those going through chemotherapy and the degree to which marijuana mitigated some of the reactions to chemotherapy?

Dr. David Casarett: Sure, that’s one of the areas in which the strongest evidence exists now, specifically for nausea associated with chemotherapy. For anybody who’s been through chemotherapy, you know that for some chemotherapy regimens, depending on the agents used, nausea can be really very severe and debilitating and last for days, sometimes weeks after the end of chemotherapy and for periods for up to a month or two, it can be very, very difficult to eat much of anything. I spoke with one man as I was researching the book, a young man in his twenties who had nausea. It was so severe after chemotherapy that he was actually thinking about stopping chemotherapy and enrolling in hospice. A twenty something year old guy with a curable lymphoma who just couldn’t take it anymore, and he turned to medical marijuana to find some relief. And there’s actually some good data, some good randomized control trials on not so much smoked marijuana, but some of the cannabinoids that are in medical marijuana.

Jeff Schechtman: One of the problems, it seems, is that it’s been very difficult to really do research on this given the nature of marijuana being classified as a class one narcotic.

Dr. David Casarett: Yeah, that’s absolutely true. The classification of a schedule one substance by the Drug Enforcement Administration is reserved for those drugs that are thought to have no medical benefit and a significant risk, often a significant risk of abuse. And because marijuana is classified in that category in the United States, it means that it’s illegal in the same way that cocaine and heroin are illegal at a federal level. And it also means the federal government isn’t going to support research, and the combination of stigma plus that lack of legal protection plus the absence of federal funding, which really drives research in this country, has made it not impossible to do research – there are researchers who have tried and done well despite those barriers – but it makes it much, much harder than it should be.

Jeff Schechtman: To what extent has that environment really negated or called into question a lot of the research that has been done, because it hasn’t been done in the more traditional ways through the more traditional channels?

Dr. David Casarett: Yeah, that’s a great thought. I think that plays out very clearly in the size of the studies that are done. There is a recent review that came out in the Journal of the American Medical Association just a couple of weeks ago that was a systematic review of studies of marijuana and for a variety of symptoms including nausea and pain and in their grading system as they graded the evidence of these clinical trials, they took off points, quality points literally and downgraded the importance of studies if the studies were small. And their definition of small is fewer than 200 people. Clinical trials are really time consuming and expensive to do, and without federal funding, it’s almost impossible to do studies that involve 200, 300 people so most studies tend to be much smaller. So right off the bat, you can see very vividly that as people rate the evidence that’s out there, the evidence base is getting downgraded and often dismissed because the funding isn’t available to do the sort of large trials that regulators, legislators and some researchers are looking for. It’s a real problem.

Jeff Schechtman: The other aspect of this is the delivery system by which marijuana is used in those cases where it may have medical value. Talk a little bit about that.

Dr. David Casarett: Sure. You’d think that would be pretty straight forward, that if you wanted to get the active ingredients of marijuana into your system – that’s THC and CBD, two molecules for the most part – you would light up a joint. But that doesn’t work for everybody. There’s some people can’t smoke for social reasons, don’t want to smoke, people who don’t want to inhale whatever comes with marijuana smoke, and so there’s been a lot of exploration of other ways of getting those active ingredients into people, some of which I tried in researching the book including, for instance, marijuana infused tea and beer and wine and ointment, none of which work pretty well. Then again, there are some techniques that work extremely well. One of the most promising, potentially, is tinctures, which consists of very small amounts of alcohol in which the active ingredients of marijuana, THC and CBD, are dissolved. And the advantage of tinctures is you can get a very reliable, reproducible dose in just a couple of drops in ways that patients can understand, know exactly what they’re getting and get the same dose reliably time after time.

Jeff Schechtman: Talk about the dosing aspect of it because it is one of the issues that comes up repeatedly in any discussion of medical marijuana, that there really isn’t a way to clearly ascertain and control dosage.

Dr. David Casarett: Well, it is a problem although it’s not entirely true that it’s impossible to do. I think the problems often arise when people use so-called edibles: marijuana infused chocolate brownies, gummy bears, what have you. The challenge there is that many people don’t know what they’re getting, and they don’t know whether a typical dose for instance, is one square of a bar of a chocolate or the entire bar, and they guess and often they guess wrong. The good news is that you can’t fatally overdose on medical marijuana, so no one is going to die because they had too much, but people do take too much sometimes and get confused and disoriented and sometimes suffer hallucinations. The solution there really is better testing and better labeling. I think an important part of all state laws should be that if you’re selling medical marijuana, whether it’s a joint or a gummy bear, people should know exactly what’s in whatever they’re buying. I mean sure there’s also other things in there like bacteria or fungus or pesticides that shouldn’t be in there, so a lot of those problems of dosing, you’re right, are significant but they can be addressed through better testing and better labeling.

Jeff Schechtman: What impact is the movement towards recreational use of marijuana in places like Colorado and Washington State, what impact is that having on the medical possibilities and medical research and medical uses at this point?

Dr. David Casarett: I’m not sure honestly. It’s really just happened in a couple of states so far, and a number of states that have medical marijuana certainly outpaces that 23 states plus the District of Columbia offer some form of legalized medical marijuana, and it’s at least under consideration in several more. My general sense is that some of the discussion about recreational marijuana is detracting from discussions about medical marijuana and research, but it can be helpful too. The testing that now exists for medical marijuana in Colorado, my understanding is, came from concerns about people using recreational marijuana and the desire to make sure that people using it recreationally had good labeling and good testing. So my understanding is that there are now patients in Colorado who can benefit from that testing and labeling and safety, not because those rules were designed for medical use, because they were designed mostly for recreational use. So there is, I think, some benefit to medical marijuana patients but in terms of actively promoting research, I haven’t seen that yet although we could see that in the future.

Jeff Schechtman: In many ways, the medical use was used and continues to be used in many places as a gateway to moving towards recreational use and one gets the feeling that as recreational use becomes more common or more acceptable, that the medical uses will really get pushed aside.

Dr. David Casarett: I think that’s possible, at least in the way that it’s used now. If you can get recreational marijuana, you wouldn’t necessarily for instance need to go to a physician and get a medical recommendation. So I think that’s true. On the other hand, I think, I hope medical research on marijuana will become more common and the research we see will be better and whether it’s obtained legally as recreational drugs or through a medical dispensary or maybe through other forms, hopefully people who use it will have a better sense of what they’re using it for, how to use it and how it can help them.

Jeff Schechtman: Talk about the medical community, and how it has addressed this issue. I mean much of the dispensing and prescribing of medical marijuana has, as I alluded to in the introduction, really been taking place in really seedy environments and really with questionable practices on the part of those in the medical community that have been doing it. Talk a little about that.

Dr. David Casarett: Well, I think that’s certainly the perception and honestly, based on what I’ve seen, that’s probably mostly true. There certainly are, particularly in California, other states too, I don’t mean to single California out but California seems to me has both a large proportion, it seems to me, of very seedy clinics. Walk down Venice Beach and I think you can see many of them. On the other hand, there are also some very, very serious physicians, many whom I spoke with in researching this book in California who really treat marijuana cannabis as a drug and they take their practice seriously and they do complete medical exams, often drawing lab tests and provide the sorts of advice that patients want and need. So there’s certainly this perception that it’s a seedy industry, and it’s a seedy industry, if it is, mostly because not many physicians have been willing to embrace it but I think those who have, have shown that there’s probably a good business model there if patients really want to start using it. They don’t want to go to a seedy clinic on Venice Beach, they want to go to a real doctor with a real license and spend 45 minutes getting advice. There is, and probably will continue to be, a good market for those physicians to provide real medical services, so they’re out there, maybe not as common as I would like, but they’re definitely out there and they’re doing good work.

Jeff Schechtman: And the mainstream medical community, how are they viewing this?

Dr. David Casarett: I think it depends. In general, I’d have to say there’s a general amount of skepticism among many physicians, including my colleagues. I would also have to say that a lot of that skepticism is probably justified being, let’s face it, there isn’t a lot of data supporting the use of medical marijuana. There’s some, and there’s more evidence for instance, than I would have thought there was when I started this project, but there isn’t as much as there is as for many other drugs that we use every day. Add to that the fact that there’s a lot of stigma associated with medical marijuana and I think a lot of physicians, my colleagues included and me frankly a year ago, would say well gosh that’s one hassle, that’s one headache I really don’t need. It’s easier for me to say that we just don’t have enough evidence. And that’s certainly not a wrong answer actually. Some physicians I think would be justified in saying look, let’s talk about this in 5 years when we have more clinical trials. But I think there are other physicians, and I count myself among them who understand that certainly, but also see the suffering patients experience and realize there actually is some data and I feel like we at least need to engage in the discussion now. Even if we engage in the discussion and decide, well, there isn’t enough evidence, I want people to know what that evidence is.

Jeff Schechtman: Is there a role or might there be a future role, both positive and negative for big pharma in all of this?

Dr. David Casarett: Yes. I think definitely, and in some ways there already is. There’s a drug called Sativex, it’s actually marketed under a couple of names, but Sativex is one of the most common. It’s a tincture, which I mentioned before, THC and CBD dissolved in small amounts of alcohol that are administered in a couple of drops under the tongue. And it’s made by a company called GW Pharmaceuticals and they’ve really been very interested in figuring out how you could use that combination of marijuana’s key ingredients in a form that’s independent of smoking or brownies or any of the other stuff you get from dispensaries. Legal, I believe, in the United Kingdom and Canada, in clinical trials in the United States. The other big area where I suspect big pharma will get very involved and probably already is to some degree, is in synthetic cannabinoids. And there’s actually synthetics that are out there now in various stages of testing, including a couple that have been approved, one that I know for sure called Nabilone that was approved back in the ‘70s and ‘80s. So there are more than a hundred synthetic cannabinoids out there. So everybody’s talking about marijuana, THC and CBD but there are plenty more in marijuana and more than a hundred synthetics, most of which have never even been tested in humans. There’s a lot of potential there. And I think the pharmaceutical industry is getting very, very interested.

Jeff Schechtman: What about the long-term impact of it? It’s not an area that again, for the reasons that we talked about earlier, because of its classification, it’s not an area that’s been fully studied. What do we know about that?

Dr. David Casarett: Well, it’s really interesting. We actually have some data on long-term effects precisely because it’s illegal. Because it’s illegal, the National Institute of Drug Abuse and other agencies and foundations have been very interested in studying long term negative effects of marijuana. So there’s actually oddly enough, probably more data on negative effects than there are on benefits because it’s an illegal drug and when something’s illegal, you study its risks and negative effects. So there have been some studies. Some studies have found for instance, that there is or could be long-term effects on brain structure and thinking. Those effects are still, I think, a little bit hypothetical. The problem is that those studies have been conducted, to my knowledge, entirely on recreational drug users and so it’s difficult to say that somebody who’s used marijuana sometimes for years, sometimes multiple times a day recreationally often with other drugs, they may have some problems with thinking and memory and they may have some structural changes in the brain but do those necessarily apply to say an administrative assistant from Oakland who uses an edible once a week to get to sleep. Is she going to have the same sorts of brain troubles two, three decades later? We don’t really know so we definitely need more evidence on what happens to medical marijuana users who are arguably different than recreational users.

Jeff Schechtman: The other aspect, and this comes back to the dosage issue in some ways that we talked about earlier, is how to measure its immediate impact in those areas where it’s been approved recreationally in Colorado, Washington and some others. There’s a lot of talk now about how to deal with drivers for example, on how to measure what would be the marijuana equivalent of blood alcohol and how that relates to dosing.

Dr. David Casarett: Yeah, that’s a big challenge. Unfortunately, there’s no, at least based on what I’ve seen in the literature and this is something that’s changing literally by the day, but based on what I’ve managed to figure out, it doesn’t seem like there’s any accurate blood test that’s the equivalent of a blood alcohol level. And there have been some studies, particularly studies that have been done in Italy that found that there really isn’t a great correlation between driving ability and either blood levels of THC or even something simple like the roadside sobriety test that involves things like walking in a straight line or touching your nose with your eyes closed that there are people who do fine on a driving test, who flunk those tests or vice versa. So at least on my reading of literature, there isn’t some test that a state trooper could use when they pull you over to determine whether you’re safe to drive or not which is a big challenge. It’s a challenge for law enforcement certainly, it’s also a challenge for people who might be using medical marijuana medically or recreationally. How do you know whether you can drive? And so my general advice if anybody asks me, you just wait a good long time; 3, 4, 5, 6 hours at least after smoking and longer after you take an edible because the effects can last longer and to be really cautious because we just don’t know.

Jeff Schechtman: Where is the FDA in all of this?

Dr. David Casarett: My understanding of the sorts of laws and legislative process consists of mostly stuff that I learned in school health and physics as a kid, so it’s pretty limited. But my limited understanding is that one of the big barriers to promoting medical marijuana or research for instance, is its classification as a schedule one substance and that’s determined by the DEA. The DEA asks for a review of the evidence and advice from the Food and Drug Administration. So my understanding is the DEA makes the decision but they ask for advice from the FDA, and the FDA is supposed to provide advice about what we know about a particular drug’s risks and benefits.

Jeff Schechtman: What is your sense of how this debate is going to proceed from this point with respect to medical use?

Dr. David Casarett: Well, it’s interesting. I think there are a lot of debates that are going on. There are debates that are unfolding in state legislatures, including the state in which I live and practice: Pennsylvania. And we’ll probably see more states adopt medical marijuana legislation. I think that will happen. I think what really needs to happen for a significant sea change, certainly in the level of evidence we have is for the federal government to reconsider how to deal with medical marijuana. One option there, I can’t predict this, but one change that many people have advocated for is rescheduling medical marijuana as class two, schedule two rather than schedule one. And my understanding is that that can be done either by Congress or a decision by the Attorney General and that would make it much easier, my understanding is from talking with researchers, it would make it much easier to do research and would help to generate evidence at a pace much more quickly than we can now.

Jeff Schechtman: Dr. David Casarett. David, thanks so much for spending time with us here on Radio WhoWhatWhy.

Dr. David Casarett: It’s been my pleasure. Thanks so much.

Jeff Schechtman: Thank you. Thank you for listening and joining us here on Radio WhoWhatWhy.

I hope you join us next week for another Radio WhoWhatWhy podcast. I’m Jeff Schechtman. If you liked this podcast, please feel to share and help others find it by rating and reviewing it on iTunes. You can also support this podcast and all the work we do by going to WhoWhatWhy.org/donate.

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