Multiple Sclerosis Discovery -- Episode 2 with Dr. Barbara Koppel

Transcript of Episode 2 with Dr. Barbara Koppel   [intro music] Host – Dan Keller  Hello, and welcome to Episode Two of Multiple Sclerosis Discovery, the Podcast of the MS Discovery Forum. I’m your host, Dan Keller.  This week’s Podcast features an interview with Dr. Barbara Koppel, whose recent review of published studies concluded that certain forms of medical cannabis can be helpful in treating some symptoms of multiple sclerosis. But first, here is a brief summary of some of the topics we’ve been covering on the MS Discovery Forum at msdiscovery.org.  First, predicting MS risk. Cardiologists can use the Framingham risk assessment tool to predict the likelihood that one of their patients will develop heart disease. But what about MS? Given that researchers have now found 110 genes related to MS risk, are we close to a formula that can predict who will develop MS and what course it will take? Disappointingly, the answer is probably not. Reporter Emily Willingham writes that “Decoding MS risk factors is less like fitting together a jigsaw puzzle and more like balancing a Jenga tower, with layer upon layer of complex interactions and unpredictable outcomes if something changes.” For those of you who may not be familiar with Jenga, it’s a children’s game popular around the world that involves balancing wooden blocks in the form of a tall tower; our article includes a helpful photo.  Next, what does the nose know about MS? Maybe a lot. Many people with MS lose their sense of smell, and now a new study involving postmortem brain samples appears to show that, contrary to earlier studies, the olfactory system is the site of significant demyelination and axonal loss. Could it be that the olfactory system is an important link between environmental exposures and MS? Stay tuned.  Finally, we’ve just posted our newest data visualization. This one is a scientific literature treemap that makes it easy to zoom in on peer-reviewed articles or clinical trial listings describing randomized, double-blind MS trials. Our own extensively researched drug development pipeline provided the source material for this visualization.  [transition music] Now, onto the interview. Dr. Barbara Koppel is Chief of Neurology at Metropolitan Hospital in New York and Professor of Clinical Neurology at New York Medical College. Along with Dr. Gary Gronseth of the University of Kansas School of Medicine, she conducted a systematic review of the literature on treating MS and other neurological diseases with medical marijuana. I caught up with Dr. Koppel at the annual meeting of the American Academy of Neurology in Philadelphia. MSDF First of all, let me ask you why do you use the term marijuana? Most people around the world use cannabis?  Dr. Koppel  There is a difference, there’s a technical difference. Cannabis, I think, only refers to some of the derivatives, and we thought medical marijuana, more people would connect with that, they would know what we were talking about; the current buzzword, but it also refers to both pills and smoked and everything else.   MSDF  And what did you look at in review, what forms of medical marijuana or compounds? Dr. Koppel  The reviews went back to studies since 1948, and the compounds that were used were pills, an oral mucosal spray that’s called nabiximols that I’d never heard of but it’s used in England, and then a few of the studies covered smoked marijuana which were marijuana cigarettes basically. MSDF  And what did you find, specifically the use of it for multiple sclerosis? Dr. Koppel  There is symptoms that it helped. It was most efficacious in spasticity, in reducing spasticity – more on the patient-related scales than the doctor Ashforth scale – but in depending on which study we looked at, the pills helped and the spray would help. It was also useful in reducing pain levels, either pain from spasms or pain from central causes – you know, burning numbness type of pain – and it reduced the number of voids, bladder voids, but some of the other bladder symptoms it had no effect on. It didn’t help tremor, which is also good to know because now we have to keep looking for other things for tremor in MS. Then we looked at other diseases, but most of the work has been done in MS. MSDF  Right now in the US there’s only one form, a pill form, approved. Do you think that you had sufficient data to make any conclusions or recommendations? Dr. Koppel  The pill forms that are available here, they’re not approved for anything other than chemotherapy-induced nausea and appetite in AIDS patients, so they were used in some of the studies and they were useful for spasticity, again, and painful spasms. The problem is that the pills are primarily THC rather than cannabinoid, so it’s hard to get up to a dose that’s working without the toxicity that comes along with THC; they they weren’t all that great. The one study using smoked marijuana was in the US, and they used marijuana cigarettes which trended towards efficacy, but the study didn’t have enough power to make any conclusions from; there weren’t enough patients basically. MSDF  Is the oral spray – which isn’t available in the US – a different composition, and does it have any differences in effect or advantages? Dr. Koppel  It has a big advantage because it’s a combination of cannabinoid – which is the part of the cannabis that you want to reduce symptoms – and THC. And the psychoactive side effects usually come from the THC as opposed to the cannabinoid, although it does have some psychoactivity as well. So the main advantages that I could find is that patients could self-titrate; they could use up to a certain numbers of pumps a day. But if they felt better with two or three pumps, they could stay at that dose. If it didn’t work at that dose, they could go up to six or seven – I forgot – the maximum. So I think that was found to be more effective, just because patients could take a dose that was adequate. It is going to be studied here, it’s the company has got testing sites mostly for epilepsy now, but it will become available here. MSDF  Have you found either in practice or from any studies whether patients were reporting self-medicating, especially with smoked form? Dr. Koppel  Yeah. The We couldn’t use those studies to make this systematic review because no one really examined them and they’re just basically testimonials or questionnaires, but there was a lot of literature that included that. And, in fact, one of the earlier papers from England, that’s why they began looking at more suitable forms of cannabis, because their patients were self-medicating by smoking, you know, just regular old marijuana and reporting that to their doctors, and and then the doctors tried to translate that into a pill form or a spray form that could be looked at more rigorously. And my patients in New York, you know, they they’re not shy. I don’t have a big MS practice, so my patients are more likely to be seizure patients. It’s not that they use it for their seizures. Every once in a while they’ll ask me if it’s okay, if it’s going to cause seizures or withdrawal, like alcohol withdrawal can cause seizures. And I can now tell them, no, it’s safe enough from that point of view. MSDF  I think you had mentioned in a news conference that there were 2 out of something like 623 patients who had did have seizure that might be attributed to use of the drug, so I take it that does not concern you. Are those small numbers, especially since you’re dealing with patients with epilepsy? Dr. Koppel  Yeah, those are small numbers. And what I’ve found is that they used to say patients with MS didn’t get seizures, but they do. There were actually four seizures that were reported, and two they didn’t blame on the drug; so they were either in the placebo group or they were patients that already had seizures. But it’s always something to worry about, but it’s such a small number that I wasn’t concerned. MSDF  While we’re on the subject, what other adverse effects did the studies you reviewed note? Dr. Koppel  The common ones that appeared in at least two two papers were things like nausea, fatigue, dizziness, fainting. In some of the studies that used the more potent forms that had more THC, they had hallucinations and depression and suicidal thoughts, but no one actually did commit suicide during the studies. MSDF  Is this a problem in MS since some of these types of symptoms or problems occur with the disease itself, could these be exacerbating it or are they directly related, do you think, to use of the drug? Dr. Koppel  That makes it complicated and that’s why you need kind of rigorous studies so that you can compare dose effects and things like that. But if a patient already has cognitive impairment, they may have trouble dealing with the side effects that, you know, that I mentioned. It’s easy to confuse that issue with the heavy users, the recreational users who end up with cognitive impairment that can be permanent. These were doses that were nothing like what people use for fun. MSDF  If this works out that it would be a useful form of drug if testing shows validity, who do you see it being recommended for? People refractory to certain other medications, or how would it be used? Dr. Koppel  That was the case with all the studies, they were allowed to try everything there was up to that point and kind of added this marijuana as a last-ditch effort. So I would say if a patient’s got uncontrolled spasticity or too much pain, they should try it. I wouldn’t really recommend it for bladder issues because it wasn’t that successful, and I definitely wouldn’t recommend it if tremor was the symptom they were trying to get rid of. So it just depends on what the patient’s telling you is bothering them the most. And, obviously, the patient has to be willing to assume all the side effects. I think one of the good things about this is some of the stigma is possibly going away so that… There’s a lot of people who assume that patients that want to try it, it’s just because they want an excuse to, you know, use recreational marijuana and get high, and it it really wasn’t the case in the studies. MSDF  It seems like it’s long past due to be rigorously testing these things. Dr. Koppel  Yes, I I agree. It has been tested in other disease states, this is just a piece of the pie where marijuana is used. It’s been used on patients with intractable pain from cancer or people with glaucoma have benefited from it; there’s usage out there. And the states that have legalized it, they don’t care which condition it’s being prescribed for. So I think it’s just neurology’s kind of lagged behind because it’s been so hard to do research on it in this country. Even in England where a lot of the studies were done, they put into their reports that it wasn’t easy to get approval. It’s not legal there either, but I guess they just were more persistent in studying it.  MSDF  Since in most of the studies that you reviewed, it was used sort of as a last resort or an add-on later, would you see that as its primary role or could it take a more prominent role? Dr. Koppel  As I said, I usually treat seizures, and what I try to do is not pile on one pill after another pill. If something seems to work, I’ll take away something that wasn’t working. So I think that’s the role for it, because if you take everything you’re going to definitely accumulate the side effects and then you really have trouble functioning. So I think if this works better than some of the existing treatments, there’s no reason to take both of them. Let me just add, it still shouldn’t be your first-line treatment, you you should still try the traditional ones first. And mon many of these trials only lasted 8 weeks; you don’t need forever to decide if something’s helping or not. MSDF  What would be the message to physicians who contemplate advising patients about medical marijuana? Dr. Koppel  I can’t tell them to go ahead and prescribe it because – for two reasons – I don’t really love the form that’s available here because it’s all THC, and it’s not FDA-approved for these conditions, so they’re still taking a chance on breaking that rule. I would advise physicians to find trials or to do a trial rather than just tell patients… even in the states where a doctor can give a card that says they agree with using medical marijuana, you you lose control of the dose and how much how much the patient smokes, and all that. So I would encourage some more traditional pills and sprays to be studied so that then they could be prescribed. MSDF  Should these prescriptions, or recommendations, really come with either informal or formal informed consent about side effects and possible things to avoid doing, like driving? Dr. Koppel  We should probably do that on a lot more pills that we’re currently prescribing. I I don’t always routinely do it, but the pharmacy tends to hand out a list of dos and don’ts, and some of the bottles are labeled don’t drive. It’s not that different from other CNS-depressing drugs, but it’s worth warning people. And, actually, I think it shows up in their urine, so if they’re going to go somewhere where a tox screen might get done, they they should have a card or a prescription that shows that it was prescribed. MSDF  This systematic review is being published in the Journal of Neurology on April 29th, and also, I guess, it’s already been endorsed by certain societies, medical societies? Dr. Koppel  They sent a summary of the findings to, I guess, other other societies that deal with the same conditions, because in addition to MS, we studied Parkinson’s and Huntington’s and Tourette’s and seizures, even though there were only two studies for that. So some of the other societies have not confirmed it but endorsed it in the sense that they agree with what we found. MSDF  I appreciate it. [transition music] Thank you for listening to Episode Two of Multiple Sclerosis Discovery. This Podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the nonprofit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is Vice President of Scientific Operations.    Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to [email protected].   [outro music]