E44 - Gaba Gaba High!

Ian Mitchell is an emergency physician, the Site Scholar for the Kamloops Family Medicine Residency Program and is occasionally photographed teaching whole rooms full of people to stick their fingers in their ears while opening their mouths really wide like they are in a silent scream.  He caught our interest with an article and talk he did about gabapentin vs cannabis.  Gabapentin was originally developed as a seizure medication, but it wasn't really good at that.  Now it is routinely used for migraines, back pain, diabetic nerve pain and a variety of other conditions.  There isn't great evidence for gabapentin and all its uses.  Cannabis is just gaining the evidence it needs to show it is good for all different types of pain and other conditions.  But it is still shunned by mainly clinicians.  Is it fair the gabapentin is commonly used and cannabis is not?  Plus we go down a cool rabbit hole into some novel uses of ketamine.
 

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Tuesday, 28 January 2020 14:10

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Episode Transcript

Dr. Ian Mitchell: Good morning, thanks. So my name is Ian Mitchell. I am an emergency physician in camps British Columbia. I work at the Royal Inland Hospital and I am also a cannabis researcher. I studied the effects of cannabis on PTSD and a study going on at UBC Okanagan. I am associate clinical professor of emergency medicine at the University of British Columbia.  I started off my career at St. Paul's Hospital and worked there for a number of years serving the population at Downtown Eastside and kind of took some of that attitude and research up to Kamloops. Where we became the first emergency department in Canada to distribute naloxone kits to anyone who had suffered an opiate overdose. Oh. I'm now moving into obviously into the cannabis field as an authorizer of cannabis prescriptions, and I'm kind of getting active in the ketamine sphere as far as treating treatment resistant depression. As emergency physicians are one of the biggest users of ketamine overall and now kind of taking that research to see what we can do outside of pain management.

Trevor:  Wow, so many interesting things there.  But the main reason we called you today is you had a talk and an article about Gabapentin verse of cannabis, which was really interesting and as a pharmacist that caught my eye immediately. So I'm gonna ask you questions about that. But how about we'll start off upfront Gabapentin. So for our listeners who've never heard of it before, what is Gabapentin and what do we do with it?

Dr. Ian Mitchell:  So Gabapentin is a medication that is generally recommended for nerve pain. It's been around for a long time and it's still one of the most commonly prescribed medications for pain is actually becoming more and more widely used now that physicians are more reluctant to prescribe opiate medications such as morphine and OxyContin. Trevor:  yeah, in the pharmacy today, I definitely have spent two or three prescriptions of Gabapentin today. So, yes, absolutely, it is common.  Now in pharmacy school. They told me that Gabapentin was originally there as a seizure medication, but didn't work all that well. I know in your talk you had a little bit of history. So how did we we get to Gabapentin being used?

Dr. Ian Mitchell:  Yes, I guess Gabapentin was, I believe, invented by Parke Davis and Boy Parke Davis. It's like the party people are the pharma world. They used to distribute cannabis and cocaine. They invented ketamine and PCP. And they also met and get a pension, which also turns out to be a drug of abuse.  So Parke Davis invented Gabapentin and originally, as you say, it was a for seizure disorders. But they quickly realized that that's not where the money is, you need to get out and get it approved for a lot of different things.  So initially they were involved with a lot of very dubious research. They published some positive studies and they hid the negative studies. One of their main researchers on Gabapentin was later imprisoned for falsifying data from research studies and completely fabricating data.  So the whole literature base that supports Gabapentin is basically supported by a criminal enterprise.  This was compounded by Parke Davis's marketing. After that of Gabapentin, where they had big payoffs to doctors who were prescribing and they were marketing Gabapentin for conditions which they knew didn't work, which wasn't approved for.  They were marketing to children, their marketing to seniors, people it was not approved for at all.  As a result of this mis-marketing, they were fined almost half a billion dollars in fines, which is one of the largest fines ever levied against Pharmaceutical Company. Still kind of chump change for with considering what they made off Gabapentin over the years they had to patent.

Trevor:  And yeah, I just I we can go into more later just to give our audience an idea like Gabapentin is, like you said, really common. And now with opioid scare is becoming even more common. Like if you go see your doctor, you have migraines that they can't treat us another way, some sort of shooting pain down your leg. They can't treat another way like anything that's quote unquote, neuropathic Gabapentin, probably the top two or three drugs that that your family physician is probably going to try throwing out at first. So it's it's use all the time.

Dr. Ian Mitchell:  This is all the time. It is actually the number one recommended medication for nerve pain. If you look at the algorithms from Canadian Pain Society and Canadian Family practice, they're strongly advocating use of the Gabapentin. The problem is that we now have much better literature. We found the hidden studies. We know that Gabapentin is probably more likely to harm you than to help you. Looking at the numbers needed to treat the side effect profile is very poor for Gabapentin.  So we're stuck with this medication that's still being widely recommended. And unfortunately, because the whole opiate thing, physicians have nothing else to offer patients. So, Gabapentin is being thrown out there just to kind of see if it works.  And you shouldn't get me wrong, there are some patients who Gabapentin works for. It's probably about one in eight, one in nine, which is the Number of people you need to treat for someone to actually have a reasonable clinical outcome, a reasonable improvement. Let's play about one rate and one in nine. So it's not zero, but it's nowhere near what people are thinking that it's as good as. And that's kind of a difficult thing to say to patients. You know, I mean, you've got this terrible nerve pain. Here's this medication that will more likely harm you than help you.  And if you're but if you're one of the lucky one and one in eight people. Terrific. Try that. It's just not a very promising message for patients.

Trevor:  OK. And now sort of on the other side. Something that I know the Canadian Medical Association has come out against.  And frankly, my College of Pharmacy and Kirk's College of Nursing… Cannabis, how does cannabis sort of stack up versus the Gabapentin for some of these nerve related pain things.

Dr. Ian Mitchell:  Well, so when we talk about neuropathic pain, cannabis has similar or probably better profile for helping the limited studies we have. The thing is this there's very limited studies because they haven't been permitted it's not been allowed to do studies in America on looking at the benefits of cannabis. You could say it harms all you want, but you're not able to get research money or research cannabis to study any benefits.  So we don't have any standards from America for that. We've got one or two studies from Canada that showed benefit in neuropathic pain.  

Trevor:  And I'm going to jump in now before we keep going down that one… you mentioned in your talk that you thought it was harder to research cannabis now post legalization than it was before. Is that. I read that right.

Dr. Ian Mitchell:  That is correct. Yeah, and you can see that in the literature right now that while there's projects being announced, there's very little being published and that's because it takes Health Canada so long approval process. So the barriers have actually increased to a point where now people are taking cannabis research to America to do it, not because they can get research dry herb, but they can get extracts there and they can do research and extract when we have got extracts here that the research process is so tiresome, so, so burdensome that people just aren't able to get it done.

Trevor:  That's crazy. OK. So, from the limited data we have on cannabis and we will call it nerve related pain, neuropathic pain, what what do we know about how cannabis works on what we're finding Gabapentin isn't so good at?

Dr. Ian Mitchell:  So, I think what we look at with general looking at chronic pain here, so it's pain is ongoing for longer than a couple of days, and I don't know that I could say that cannabis is necessary, good treatment for acute pain. We don't have that data yet, but for chronic pain, it seems to be as good, certainly better than Gabapentin. And that's not just neuropathic pain. That's throws all manners of pain. So I would say that it's likely more effective, has fewer side effects, but because the stigma, it's ranked far lower than medications have significantly more harm like Gabapentin and didn't like Tramacet, which I could go on a whole other podcast about.

Trevor:  Yeah. No. Tramacet not my favorite either. Around here, honestly, it's just on price, but will leave that alone for the moment.  But so for pain, because there's so many different things in cannabis. You know, the two that everyone's heard about, the THC CBD. Then we have probably 100 minor cannabinoids. We have Terpenes. Do we have any idea what part for cannabis is good for pain or is that still an open question?

Dr. Ian Mitchell:  I'd say that's open question. I think we don't have good evidence that CBD is analgesic, that CBD relieves pain. I think we can say that CBD is likely anti-inflammatory anti-anxiety and those are qualities of pain that can be helpful. But if you're looking at the heavy lifting for pain, particular neuropathic pain, it's THC and that's really what the studies are looking at. The challenge is to deliver THC in a way that people are still capable of doing, going about their business and not being impaired. And often that comes by combining the THC with the CBD. So for the patients that I treat who have neuropathy pain generally I'm recommending a nighttime product of THC and CBD. I always invite people to try just plain CBD during the day, first off, just to see if that is enough to manage the pain and help get them through. They're just going to feel that's very safe. They may need some THC during the day, and then if they're doing that, then we talk a little bit about impairment and micro dosing and how they can manage to deal with their pain and still be able to do what they want to do during the day.

Trevor:  OK. And because I'm a pharmacist and somewhat obsessed with this, how are you getting this into patients? Are you telling them to vape it or take an oil because they can change the dose, a capsule? Do you have any thoughts that way?

Dr. Ian Mitchell:  So generally, I'm not a big fan of smoking. I don't think doctors are getting banned smoking. So, I am happy to have people vape, But most of my patients nowadays, my population tends to run between 60 and 80. So they're just not smokers, they do not want to vape. So, they're really taking the oils. And that's the number one product I'm looking at the patients right now and they're starting predominately at nighttime. So, they kind of build up some tolerance and then they will start to bring some of that into the day.

Trevor:  And anecdotally seems to be going OK with the patients that you're going. You're you're using.

Dr. Ian Mitchell:  You know, I've had some terrific response. I don't expect to make everybody better, but no, I have people that, you know, they come and say I’ve changed their lives in a more frequent way than I do in emergency medicine, which is is that of a different feeling. But I've certainly had great success with treating people with nerve pain. And certainly, they've also been able to come off their opiates and Gabapentin and that's often something we address with their visits ongoing. As you know, they may when I start tapering down some of their other medications.

Trevor:  OK. And sorry jumping back to Gabapentin in a bit. I don't think we touched on it earlier. Gabapentin you know, we like to mainstream bodies are promoting it as, you know, a cure all for many, many things.  But they don't talk often about the abuse potential of Gabapentin, you want to touch on that?

Dr. Ian Mitchell:  Absolutely. So it is. It's not the most widely abused drug, but we certainly understand that it can be abused. One thing to know is it increases the effects of opiates and also increase the death rate, associated with opiates. So if you're taking the two together, you're more likely to die. But on its own, it can produce a high and it's kind of a poor man's high to take but. So that's kind of come up and we perceive that a lot more people in the prison population, people really cussing Gabapentin.  I can’t say I see a lot of overdose from it, but lyrica has become, very popular drug abuse, particularly in the United Kingdom and has been rescheduled as a consequence.

Trevor:  That surprised me when I read that in your talk again, maybe it shouldn't have. But a lot of the physicians in my area anyway are kind of steering clear of Gabapentin when they can because some of the things have been coming up about it, but they've been switching instead to Lyrica or pregabalin. So I take it you're implying that's not necessarily a good switch?

Dr. Ian Mitchell:  I would say the abuse potential is probably higher. It seems we've certainly heard more about Lyrica abuse than Gabapentin abuse. But I would say it's mostly the more expensive form of Gabapentin. There's still no evidence that it works any better than Gabapentin did, although it played us have fewer side effects. But I think there's also this concern, you mentioned about the doctors going away from Gabapentin then come back to it. It is just prescribed for everything you say alcohol withdraw Benzodiazepine withdrawal, chronic pain, acute pain, arthritis, painful periods. I think one of the criticisms that the Canadian Medical Association sometimes has is that people say, well, cannabis cures everything. And that's exactly what's going on with Gabapentin and Gabapentin appears to cure everything and you know that by how many prescriptions you fill for it?

Trevor:  Yes. No, absolutely that sounds bad, but it's giving out like Tic Tacs around here. I'm not disparaging my local doctors. I think they're doing the best they can with the tools they have. But yes, if we can't figure out what kind of pain it is usually Gabapentin is tried with it sooner or later.

Dr. Ian Mitchell:  And that kind of brings up, I don't know, maybe an uncomfortable thought about, you know, doctor patient relationship is like when  people want something and they kind of you know, if they don't have something, they feel that they have not been treated or, you know, that they have not received proper medical care. So, you know, is this just a placebo or something to give people and hope it works and it may. But realistically, if we all know that it doesn't work, how can you keep on conscious prescribing it.

Trevor:  No. Fair enough.  And while that goes down, like you said, a whole of the different podcast. It would be nice if we had easier access to places like pain clinics when, you know, the GP is sort of run out of everything and in her bag of tricks and wants to try something else around here anyway, it can easily take a year more to get them into a pain clinic to try something else.

Dr. Ian Mitchell:  And then that's absolute same case with where I work. There's very limited access to pain facilities. So without those people are just going to doctor and it used to be they would get lots of opiates and now they're getting lots of Gabapentin. It's just it's and it's not the most harmful thing, but it's not really helpful either. And you can see that, you know, as opiate prescribing gone down, Gabapentin prescribing has gone way up, even as more and more studies show it's ineffective. And there's good research showing that doctors who take more money from pharmaceutical companies are much more likely prescribed Lyrica in the upmarket version, they're much more likely to prescribe brand name versions of Gabapentin.

Trevor:  Yeah. OK. For something completely different, because I think we have time to for this in. So, we're normally a Cannabis podcast. But there was a really interesting picture of you in front of a large group of people and everybody seemed to be yawning and sticking their fingers in their ears.  What was that about?

Dr. Ian Mitchell:  So I was teaching about ketamine to a group of practitioners who shouldn't using it for treatment resistant depression.  And this is a kind of relatively new thing as the FDA just approved a form of ketamine, nasal inhaler for treatment of depression in the US?  Now, I give ketamine in much larger doses in the emergency department and occasionally that can cause laryngospasm, which is where your vocal cords spasm up and close off your airway, which is pretty dramatic and unsettling thing to have happened because then people can't breathe. And so if you do this maneuver where you stick the fingers on both sides and kind of push towards the center, that's what causes pain and clears the airway and can clear up that laryngospasm. So I was just an opportunity for a great picture and a great conference I was at.

Trevor:  And like I said, normally cannabis, but I'll pick your brain a little bit more about this. So we're compounding pharmacy,  So when I use ketamine, I'm probably putting it in cream that someone is going to rub on some neuropathic pain. How is Ketamine? And maybe we should do both. If you can tell the audience what what ketamine is usually used for and like anesthetics and then how do we think it might be doing something for depression?

Dr. Ian Mitchell:  Absolutely. So, yeah, ketamine, as you say, is a dissociative anesthetic. Kind of makes people just go away for a little while. A lot of people familiar with it as a horse tranquilizer that's kind of what I often hear it referred to. But I give it to children for a procedure. So I gave it to a boy last night to fix a fractured arm.

Trevor:  It's an injection you're giving him?

Dr. Ian Mitchell:  So I'm giving this intravenously. So what? And that's really the use that people are familiar with. But right now in British Columbia, ambulances now carry nasal inhalers of ketamine for acute pain management, that is the result of a study that was done by a guy called Gary Andolfatto, who was an emergency physician who fell, broke his leg, hiked for five miles through the wilderness, using his bike as a crutch before he could call out to get help. The ambulance came and only had nitrous oxide, laughing, gas or pain medication. So we designed the study and carried out. And now ketamine is being used in ambulance to treat acute pain. My nasal sprayer, so you can give up my nasal spray and the is about 50 percent when we're talking about use in the treatment resistant depression. People are going to be using the nasal inhaler, which is approved from the state. But I'm also seeing some sublingual usage with sublingual… a lozenge that's the right word for it. Yep. So that's at this conference I was at, there was a pharmacist there who was 3D printing, ketamine lozenges to give to patients feelings of depression. So pretty advanced stuff.

Trevor:  Wow, that's that's really cool. Just a little more on ketamine now when we started putting giving creams for neuropathic pain. We use it because it's an NMDA receptor antagonist and you know, a lot of other analgesics can get at the NMDA receptor. But are our local anesthetists got very excited because apparently there is a whole bunch of safety protocols they've got to use when they use ketamine as an anesthetic. Can you just tell the audience why the anesthetists are or we're a little concerned about using ketamine for just run of the mill pain and how we avoid some of those problems, if we're doing it for four depressions, bring it up people's noses.

Dr. Ian Mitchell:  Yeah, there's a kind of it's a bit of a turf war kind of thing. And anesthetists are very protective of it. But ketamine is one of the safest medications around. It's used in battlefield medicine. You can give someone a battlefield and chop off the leg and do that surgery. So the concerns are mostly overblown. There's a lot of regulatory stuff involved and just because it's an anesthetic. But what we're talking about here is using in sub anesthetic doses. There's lots of good data and there's now FDA data saying you can do this and do it in a safe manner. The concerns may become a little bit about abuse. Obviously don't want these sprayers going missing. And, you know, ketamine is known to be a drug of abuse as well, but it's realistically safer than all the narcotics we're using. So I'm not sure what the huge issue is.

Trevor:  Oh, thank you. This has been a really fascinating side track all the way from Cannabis.

Oh, but you did ask me about the mechanism. Tell me about the mechanism.

Dr. Ian Mitchell:  So there's this weird thing in depression where parts of your brain are less electrically active than normal. So they're just kind of, I'd say, likely silent. Quiet brain areas. And when you take ketamine within a couple of hours, you start to get growth of synapses and dendrites off your neurons. So you get not new neurons, they get more connectivity and those areas, your brain light up again.

Trevor:  Are you telling me that happens curing depression in a couple hours is supposed to.

Dr. Ian Mitchell:  So that's the whole thing about ketamine is it will fix depression within a couple of hours. The effects last after the week.

Trevor:  What one dose of ketamine in a couple hours. I feel better and my depression is left for a week.

Dr. Ian Mitchell:  And so suicidality is actually this infusion data study, one infusion can fix 30 percent of suicidality within a several hours. Two infusions can fix 60 percent of suicidality.

Trevor:  That’s crazy.  That sounds like electroconvulsive therapy, doesn't it?

Dr. Ian Mitchell:  Well, the thing is, you don't have to do it that way. You can you can just do it I.V. and people just sit there and chill and they're fine. They don't need to go for electroshock therapy, which, you know, honestly isn't available to us anyway. Well, what I would love to do is have the ability to give people internasal ketamine who are suicidal and my emergency treatment. So they don't have to lock them up in a room without their phone and clothe and away from natural light because that doesn't tend to improve their mood much.

Trevor:  No, no.  And I'm jumping all over the place for that. Remind me something else in your Talk Back. Back again, Gabapentin. You were talking to Gabapentin. And suicidal ideation, especially in young people, will call it 15 to 24 ish. I never heard that before. That's the thing, because, frankly, we we have lots of, say, teenage girls with migraines who periodically get Gabapentin. Is this something I should be aware of?

Dr. Ian Mitchell:  It is probably something you should be aware of.  This comes from a recent Swedish study I think published earlier this year. There should be a link in my thing to it, but if you look up, it was a paper on Gabapentin on suicidal behavior and driving impairment, which they also found with Gabapentin.  I don't how much you counsel your patients about the driving impairment

Trevor:  That has come up, but suicide has never come up.

Dr. Ian Mitchell:  Yeah, Suicide they found it was more common in younger people. And this is precisely the people at CMJ warn, you know, they've got developing brains and they shouldn't be exposed to Cannabis but Gabapentin just fine. So I don't know. You know, again, it just goes to double standard and the stigma involved in cannabis.

Trevor:  Well, so much, so much to learn. Now we are running short on time. So before I forget, is there anything else, cannabis or otherwise, that you think are our audience should know before? Before I let you go?

Dr. Ian Mitchell:  You know, I'm going to say that to people. If you're on Gabapentin and it's working for you. Great. If it's not working for you, it is associated with withdrawal symptoms. So, you know, a lot of people just take medications because they’ve been on them for a long time. So if you own, say, 900 milligrams of Gabapentin, look at going off at a decreasing dose to six hundred a couple of weeks. Keeping it down to 300.  Keep track of what those changes, how those changes make you feel. And if you don't notice any difference, then why would you keep taking a medication that has no side effects?

Trevor:  I think that's great advice. Dr. Mitchell. That was great. Thank you very much for being on Reefer Medness. We really enjoyed talking with you.

Dr. Ian Mitchell:  I am happy to come back anytime. We should talk about ketamine, cannibals or whatever.

 

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