Medical Cannabis Revisited: A Podcast with David Casarett and Eloise Theisen

Eric 00:01

Welcome to the GeriPal podcast. This is Eric Widera.

Alex 00:03

This is Alex Smith.

Eric 00:04

And, Alex, who do we have with us today?

Alex 00:06

Today we are delighted to welcome David Casarret, who is a palliative care doctor and Researcher in Chief of Palliative Care at Duke and author of Stoned: A Doctor’s Case for Medical Marijuana. His TED talk on this issue has received over 3 million views.

Eric 00:21

3 million.

Alex 00:22

3 million. David, welcome to the GeriPal podcast.

David 00:26

Thanks. You got me laughing already.

Alex 00:30

And we are also delighted to welcome Eloise Theisen, who’s a palliative care nurse practitioner at Stanford and CEO and co-counder of Radical Health Clinician Network, which helps patients use cannabis to treat chronic and age related illness. Eloise, welcome to the GeriPal podcast.

Eloise 00:47

Thanks so much for having me.

Eric 00:49

And I just want a big shout out to Alex Gamble, who said, we have to get Eloise on a podcast to talk about this topic. I am super excited to have you on, Eloise.

Eloise 00:59

Thank you so much. Yes.

Eric 01:01

So we’re going to be talking about medical cannabis, kind of revisiting it, because we actually had one in 2021 with Ben Han and Bree Johnston talking about cannabis, including increasing use in older adults and less perceived risk amongst older adults using medical cannabis. But before we get back into this subject, Eloise, I think you have a song request.

Eloise 01:27

Yep.

Eric 01:27

Man. The amount of songs you could choose. [laughter]

Alex 01:30

From the podcast, both of you had some great suggestions.

Eric 01:34

Yeah.

Alex 01:35

So thank you for all those terrific suggestions.

Eric 01:37

Puff the Magic dragon. [laughter]

Alex 01:39

Material here for songs related to medical marijuana or marijuana in general.

Eric 01:43

Eloise, what to pick?

Eloise 01:45

Well, David had a good one, but I picked How to Get You Into my Life by the Beatles.

Eric 01:55

Why did you pick this song?

Eloise 01:58

The song was actually, Paul McCartney came out and said the song was actually about marijuana that he wrote back in the day. And if you listen to the lyrics, it really does talk about how much he enjoys using it and wants to get it into his life every day. And I think it represents the euphoric component of cannabis that we often don’t discuss and fear. There’s a lot of euphoria phobia out there, so I think it’s a great song.

Alex 02:23

Terrific. All right, here’s a little bit.

Alex 02:26

(singing)

Eric 03:30

That’s great. So, again, so many other songs. I think, Alex, you’re going to finish with the entire album of the Chronic by doctor Dre. After? [laughter]

Eric 03:43

…trying to get Alex to do some rap. [laughter]

Alex 03:46

One of these days…

Eric 03:50

I’d like to start off just hearing from both of you why you got interested in this subject. And, David, I’m going to start off with you because you wrote an entire book about this. What? Wait, Alex is giving me…is that a…

Alex 04:05

It’s a gummy. Do you want one? You don’t want the gummy?

Eric 04:10

No, it’s okay. Alex.

David 04:15

It’s going to get really, really interesting. [laughter]

Alex 04:19

For our listeners. These are vitamins. [laughter]

David 04:24

That’s what they all say. Yes. Eric, do you want me to go first?

Eric 04:29

Yeah, go ahead, David.

David 04:31

Yes. This is back in, I don’t know, like 2014 maybe. Pennsylvania was thinking about legalizing medical cannabis, and I got involved in some of those advocacy efforts, worked with a lot of really strong, powerful moms of kids with epilepsy who were really pretty inspiring because they just would not take no for an answer and were not awed or overwhelmed or intimidated by lawmakers in Harrisburg. They just kept at it. So that kind of raised my awareness. And then I met a patient in clinic once who asked me a lot of really intelligent questions about medical cannabis, what it does.

She had pancreatic cancer, bad neuropathic pain. And, you know, I tried to give her some advice and actually did some research and looked up what I could. And midway through our encounter together, she told me that she was actually using medical cannabis. And she was kind of asking me what I knew about it as a test to figure out whether I was worth sticking with. And this is. This is pre legalization. So she was. I don’t know where she was getting it, probably from her grandson. But that. That was really eye opening to me, both because I was learning there’s a lot of. Not a lot, but back then, some science, certainly more science than I realized.

Eric 05:44

Existed because she handed you a packet of RCT’s, right? Or studies?

David 05:49

She did, and she had my email address. So for a period of a couple weeks, every night, I would get home and check my email and there’d be more pubmed references. She was a retired professor at Penn. And so I was interested in this. I was still kind of skeptical, and so I don’t think I’ve had told the story widely, but my initial pitch to Random House, which is my publisher at the time, was that I was going to write an expose on the crappy science behind cannabis. And then I started looking into it and realized actually, the science wasn’t perfect, but it wasn’t crappy at all.

And there’s actually some decent stuff there. So I was in the awkward position after I got the book deal, going back to my editor at Random House, Nikki Papadopoulos, and saying, well, actually, could we change the frame a little bit more positive? And she, to her credit, was. Was really open and supportive of that. But that was, that was it. It was a little bit of advocacy. And then one patient who really knew more about a topic than I did, which unfortunately happens much more often.

Eric 06:53

I loved your book. I read in one sitting last night. It was absolutely fabulous. Tons of interviews, bringing in real patients, talking about the science, both. What do we know works, what do we think as far as risks, side effects that we have to worry about? I also love the idea. Like, you were talking with one patient who was in hospice, and he got a lot out of medical cannabis. He actually joined a hospice. Right, that allowed it, but then they were worried about giving somebody medical cannabis, so they no longer included that as a potential benefit.

But they would give somebody morphine, Benzo, this comfort kit, admission, which, honestly, many of those things don’t have a great amount of evidence. But the one thing that he felt like he really got the most benefit from, from his pain, was cannabis, and that was not something that was allowed.

David 07:51

Yeah. Which is eye opening to me as it is, I think, to many of us. And you could say the same thing about insurance companies. Insurance companies will pay for a lot of drugs that have really not a whole lot of evidence at a lot of costs. But to this day, I haven’t heard of an insurance company that’s willing to cover cannabis. It’s going to change gradually, especially if we talk about rescheduling cannabis. But right now.

Eric 08:13

Yeah. Or if a pharma company can make a really good pill, they’ll pay for it. Eloise, how’d you get interested in this?

Eloise 08:22

Yeah, I was in a pretty significant car accident about 1314 years ago that left me disabled and in chronic pain. And so I, like many patients, ended up on multiple medications after a certain amount of time. We were trying to treat the side effects of one medication, and I ended up on polypharmacy at a pretty young age and ended up with serotonin syndrome. That put me in the emergency room. And it was at that moment that I thought, okay, there’s got to be something else out there that can help me. And I started to use cannabis, and it helped me get off all of my medications. And I returned to school to become a nurse practitioner.

I’d been a nurse at the time, and I went back to do my clinicals in an oncology clinic locally. And every day, patients were asking me about it. I’d close the door, and they’d whisper and say, what do you think about marijuana? And I’d be like, I don’t know why we’re whispering. And then I started to wonder, do I have this green aura about me? I had come so far in my own research and curiosity for myself, but never thought it would go any further. And I decided at that point to hang a shingle and start a clinic with a physician. That allowed us to actually teach patients how to use it, what to expect to talk about dosing and drug to drug interactions. And I kind of just took off from there.

Eric 09:48

That’s great. And for the listeners not watching YouTube, I’d see maybe it was the big weed magazine thing that you have in the background, Eloise, that got them talking, because it is very stigmatized. Right. This is something that. And we learned this on our last, last podcast with Ben Hot. You know, two decades ago, usage in older adults was nearly zero for cannabis, marijuana. But now I think it was like 5% when he checked it last. The numbers are increasing, which will probably be only continuing to increase with the baby boomer generation becoming older. Is that your feeling, too? Does that have face validity?

Eloise 10:29

Yeah, I think what we saw in California was, prior to legalization, there was curiosity, but also a lot of their healthcare professionals didn’t know enough about it, so they didn’t discuss it with them. And the process was you’d go and you’d get a letter from a recommendation from a doctor, and then you’d go into a dispensary, and it was really overwhelming. And then in 2018, when adult use was allowed in California, I think it gave people more permission, but the stigma is still there. I mean, I had a woman who completely got her life back.

She was in chronic pain, and she started using cannabis, and she was able to go back to yoga and be active. And she was absolutely terrified to tell her adult children, because she spent her whole life telling them to say no to marijuana. And I said, they have to know that you’re doing better. Aren’t they asking you, what are you doing, mom? What’s changed? And she said, oh, I just told them I’m doing some alternative stuff. And she never confessed.

David 11:27

It still is. I actually do some consulting work with a company called the Farmstand that’s based in a community called the Villages in Florida. And it’s to the degree that any retirement community could be described as a party town, this is a party town made the news not too long ago for having a really high incidence of STD’s. For instance, Friday night, Saturday night parties are of community wide. But I gave this talk, and one of the questions I asked a group of maybe 150 residents was, do you talk to your healthcare provider about your medical cannabis use?

After I asked many people how many used it, and I would say less than one in ten were willing to talk to their healthcare provider. This is a community that really loves to live well and is out there and doing what they want to do and enjoying life as much as they can. And yet, stigma about cannabis really, really held them back. It was really, really impressive to me. So I think stigma is still a huge issue.

Alex 12:24

So one in ten people who said they were using it told their healthcare provider, and the other nine out of ten did not.

David 12:31

Yeah, if you believe the results of an informal.

Alex 12:33

Sure, sure.

David 12:34

Yeah. It was something like one in ten, and a lot of people weren’t.

Eric 12:38

So how do you both bring it up? And maybe Eloise, like, in your Stanford perspective as a nurse practitioner, not in, like, your cannabis clinic perspective, I’m guessing.

Alex 12:49

They come there for some.

Eloise 12:52

Yeah, that’s kind of a no brainer, right? Yeah, I mean, I think one of the things I’m proud of is that, you know, Stanford was seeking someone with my knowledge for their clinic because patients wanted alternatives to the medications, the pharmaceuticals that were being offered. And so I have free range to talk to my patients about cannabis, and it’s in my bio. So sometimes they are seeking me out and asking to meet with me personally, or they read my bio, and then it comes out during the conversation where they’ll admit other times. I. You know, one of my favorite stories was a gentleman with pancreatic cancer who had intractable nausea and vomiting and nothing worked.

And you know, I thought, well, here’s someone I would actually bring it up with. But he was a DA for the last 25 years, and he did the marijuana convictions in his county. And I thought, oh, my gosh, you know, am I going to bring this up to this, this guy? But I just decided, I said, you know, his meeting over video with him and his wife, and I said, you know, I have a suggestion. I don’t know how you’re going to feel about it. And they both got these big grins on their face because they just knew that I was going to say, you know, what do you think about cannabis? And they were relieved because their friends were bringing over bags of this stuff, and they’re like, we don’t know what to do with it. So I was able to guide them. I put them on a transdermal cannabis patch. His nausea and vomiting stopped. His quality of life went up. I mean, it was really kind of, you know, when it works, it can be quite magical.

Eric 14:22

David, do you talk about it with your patients? Do you recommend it or prescribe it?

David 14:28

Yeah, I mean, it’s a slightly different situation for me, more than slightly. Medical cannabis is not legal in North Carolina, so there are definitely some limits. I mean, I haven’t heard of anybody getting in trouble with state medical board for recommending it. I generally, except in rare circumstances, don’t recommend it to a particular patient. I always, always, always, almost always ask what people are using. Are there any medications or alternative remedies you’re using that aren’t in the medical chart that we should know about? Because if I’m recommending benzos or opioids, I want to know what else they’re using.

It’s not me being big brotherish. I want to know what the milieu is that I’m throwing these scheduled drugs into. So I ask all the time, and then usually, short of getting the recommendation, I’m happy to talk with patients about what the evidence shows if they’re using it for neuropathic pain, happy to discuss what we know. One large scale meta analysis found benefits and they didn’t. Here’s what we know, here’s what we think we know, and that’s usually the way I approach it.

Eric 15:37

So let’s break that down. What do we know? Where is the evidence the best for the use of medical cannabis?

Eloise 15:47

I would say chronic pain, but not specifically malignant chronic pain. There’s concrete evidence that it can help with chronic pain in older and adults.

David 15:59

Yeah, yeah, that would probably be at the top of my list, too, although it’s kind of humbling. I mean, I used to say chronic pain for sure, especially neuropathic pain, both because the evidence I thought was good and also because that’s where we get tripped up. Um, opioids don’t work so well. A lot of people don’t like gabapentin lyrica. Sometimes we do methadone here. Buprenorphine maybe, but there. The studies I mentioned before, Mark Ware did a big meta analysis that found some benefit from neuropathic pain. But there was a Cochrane review that was almost identical in methods. Maybe it occluded. One other study, I think, that came out a couple of years later that found no benefit. So I’m still convinced it for neuropathic pain, but the data are messier than I like.

Eric 16:44

How much is it? Because cannabis could mean a lot of things, so it could just mean THC, it could be the CBD, it could be a combination of both. It could be the entire plant with everything else in it, and then it could be. How are you actually delivering it?

Alex 17:00

So many different things.

Eric 17:02

Are you vaping it? Transdermaling it?

David 17:06

Yeah, it’s a little repositories. Palliative care works. And then another study says that palliative care doesn’t work, but not like what’s in the syringe.

Eloise 17:16

Yeah. And we don’t really look at dosages when we’re doing these studies. So I think that’s one of the challenges we have, is that, you know, you can look at these studies that will say, well, they smoked anywhere from, you know, one to ten joints a day, and we don’t know the THC content or the other cannabinoid content. So I think it’s. We need more studies that really hone in on the dosages of the different.

Eric 17:38

Cannabinoids, because the amount of THC to CBD is going to vary potentially dramatically. Right. From one source to another.

Eloise 17:49

Yeah, yeah. And we’re not. And even the evidence on CBD, I think, is promoted as. It’s going to be like a dimmer switch for THC. Right. It’s going to help lessen some of those unwanted effects. But if you. The evidence is all over the place. It’s like, some say it makes the THC less sedating, some says that some CBD can make it more sedating. So it’s really hard to know. What should I try?

Eric 18:18

And reading your book, David, I get a sense that many of the unwanted, well, I wouldn’t say unwanted, maybe for medical marijuana, a medical cannabis, the unwanted effects, the euphoria, the high feelings that’s coming from THC.

David 18:36

That’s true.

Eric 18:37

The sedation versus CBD may not have as many of those or if any of those side effects. Is that right?

David 18:46

Yeah, I mean, I usually say that CBD isn’t psychoactive, and then I have to correct myself and say, well, in really high doses, for instance, there have been a couple of studies showing that CBD in really high doses, 500, 600 milligrams, can reduce social anxiety. So there’s probably some psychoactive effect of CBD, but compared to THC, it’s essentially zero. At least I appreciate Eloise’s thoughts. That’s my take on it.

Eric 19:10

What’s your take, Eloise?

Eloise 19:12

I usually say it’s non euphoric because it is psychoactive. Yeah. And THC is known for the euphoric effects and it’s also biphasic. So in small doses that it can be euphoric, but in large doses it can be dysphoric and people can have that paranoia and anxiety, very unpleasant experience.

Eric 19:33

Yeah, that’s a funny thing, right? Some people helps. We’ll get into anxiety in a brief second. Some people may feel less anxious, some people may get very anxious. And then, David, I also learned from your book, if they start withdrawing from their marijuana or as the kinetic get out of your system, you may actually feel more anxious. So you’re actually treating the anxiety from using a lot of cannabis, is that right?

David 20:00

Yeah, I think so. I mean, I think, you know, people talk about withdrawal syndrome and it is an official DSM for diagnosis, but I’m not sure it’s. I mean, I haven’t seen it the way you see, you know, alcohol withdrawal, for instance, or opioid withdrawal, but there probably something. There’s something there. And for people who use cannabis for sleep, which we haven’t talked about, but I’ve certainly heard of people who get into the habit, like with Ambien or anything else, who use it every night for weeks and you miss a dose and you really have trouble getting to sleep. So there certainly is some tolerance that builds up. I wouldn’t want to make too much of that because in the overall scheme of things, it’s not like withdrawal or tolerance to other psychoactive drugs.

Eric 20:45

Okay, so maybe some evidence for chronic pain, maybe neuropathic pain, it’s not going to bring your pain down to zero, right? It’s gonna maybe, like other agents, maybe reduce it by a couple points out of a ten point scale. Is that sound about right? And is it the THC or the CBD or the combination.

Eloise 21:08

It depends. I mean, there’s other cannabinoids that are coming out, too, that are showing some evidence, like CBG seems to play a pretty significant role in neuropathic pain and anxiety. There’s also CBD, a and THCA, which are considered the raw forms that can help with pain and anxiety, which aren’t as well studied or available.

Eric 21:30

Yeah. And are all those are naturally occurring cannabinoids? Like, if you smoke it, you get those or vaporize it.

Eloise 21:38

CBD A and t. Any of the cannabinoids that have an a afterwards are considered raw, and then they become neutralized through heat. So either they’re heated in an oven or they’re smoked, and then I. THCA becomes THC through that heating process.

David 21:56

But that is an important point. I mean, when you look at the cannabinoids in the cannabis plant, we all focus on THC. That’s kind of the popular kid at the party. That’s the cannabinoid that’s been the best studied.

Eric 22:06

That’s Marinol right there. Right. We have a pill for that.

David 22:09

Exactly. But there are a whole bunch of others, some of which we’re starting to understand, some of which just sit in test tubes somewhere. But we know what they are, what they do. But there are well over 100 cannabinoids that have been isolated so far, of which we talk mostly about THC and CBD. But that’s really tip of the iceberg.

Alex 22:26

Hmm.

Eric 22:28

And then what? Before, because I want to talk about dosing and preparations, but before we do that, other things that we have a pretty good feeling that medical cannabis may help it. So we talked about pediatric seizures. That was the pediatric part, so pretty good evidence. Right. Pain. Anything else?

Eloise 22:48

I would say one of the common reasons in palliative that people want to meet with me is they use cannabis for appetite stimulation. And I would say the evidence is pretty low. And often I don’t see great results, particularly in females versus males. There’s not a lot of evidence to back that up. It’s just what I have observed over the years.

Eric 23:08

But, yeah, yeah, I got to say, I’ve never seen any effect from Marinole, just that THC component. David, your thoughts on anorexia, cachexia?

David 23:20

Yeah, pretty much the same. I mean, I think in theory there’s a reason it should work, and there’s some regulation of some appetite related hormones like ghrelin. So we know from lab research that there should be an effect, and there’s some effect on appetite. I think anybody who’s used cannabis recreationally.

Eric 23:38

Knows that gets the munchies.

David 23:40

Yeah, I just don’t think it’s enough of an effect to wipe out the cachex syndromes that we get in heart failure, lung disease, or cancer. It’s like trying to kill an elephant in the fly swatter.

Eric 23:51

What about nausea, vomiting?

Eloise 23:53

It’s kind of hit or miss, I would say. What do you think, David?

David 23:56

The same. I think. I haven’t seen a whole lot of evidence, but again, I think there’s enough background biochemistry evidence that it can alter serotonin metabolism number one. And number two, honestly, I’ve just heard so many anecdotal reports, and I realize that’s anecdotal medicine. It’s not evidence based medicine. But you hear patients telling you again and again and again, look, chemotherapy is a whole different ballgame. If I can have a joint in the parking lot before I drive home some of that placebo effect, but I’ve got to believe there’s something real there.

Eric 24:34

And then spasticity or cramps in M.S.

Eloise 24:40

I don’t see a lot of those patients. What about you, David?

David 24:44

I don’t. But a big company out there, GW Pharmaceuticals. Yeah, and hundreds of millions of dollars in trials and FDA approvals. So the official answer would probably have to be, if you believe the whole.

Eric 25:00

Drug development approval process, what drug is that?

David 25:03

Satabx.

Eric 25:06

And then any other conditions that we think it works in besides the one we’ve talked about right now.

David 25:12

Yeah, I would add sleep to that. There isn’t a whole lot of randomized controlled trial data that I’ve seen. But if you look at some of the sativax studies, they looked at side effects. And one side effect that comes up often was the side effect of being sleepy, which, if you’ve used it, you don’t really need a researcher to tell.

Eric 25:31

You how much of that is like a benzo. Yeah, it makes you sleepy, but it doesn’t help with sleep architecture. People feeling more wakeful during the day, rested. Do we have any evidence around those. Those outcomes?

David 25:47

No. I mean, if I know it’s not doing much for sleep architecture, and it makes you fall asleep more quickly, depending on the preparation. I work with a company called Curio. It’s based in Maryland, now in multiple states, but has a product that has a sustained release form. So you get an initial dose and then a little bit later, two or three in the morning to help you stay asleep. For those folks who. Whose problem is actually sustaining sleep, not initiating. And a lot of rave reviews, but I don’t have any idea what architecture.

Eric 26:19

Well, let’s get to the nitty gritty.

Eloise 26:22

I do want to add one thing. Neuropsychiatric symptoms in dementia patients. That’s where I’m seeing cannabinoids have a significant impact for those patients.

Alex 26:33

Which kind of symptoms?

Eric 26:34

Like behavioral symptoms?

Eloise 26:36

The behavioral symptoms, yeah, the agitation, anxiety. Calms them down.

Eric 26:42

Yeah.

David 26:42

I discovered that one of the interviews I did for stoned was with a filmmaker in Israel whose debut film, I think, was based on time he spent in a nursing home helping older adults to use cannabis. And he said that the result was just magical. And there’s actually a paper published in the dementia Congress that happened in Brazil just a month or two ago that reported on exactly what Eloise is saying. Reduction in agitation symptoms, which, especially in a world where we’re under pressure to reduce or eliminate the use of antipsychotics, for instance, for those patients, having an alternative is really potentially very cool.

Eric 27:21

So how do you get, I know in your book, for those, again, I’m going to plug stone, I think, in Israel, for somebody who couldn’t actually smoke it themselves, the filmmaker actually blew the smoke in his face. Is that right?

Alex 27:38

Interesting delivery mechanism. That’s something we teach in palliative care fellowship.

David 27:45

And speak for yourself, we do things a little bit differently at Duke.

Eric 27:51

What’s the delivery that you recommend or how it’s done? Eloise, what do you do?

Eloise 27:57

Well, often the dementia patients can get paranoid and refuse their medication. So gummies tend to work the best because it’s a sweet little treat that they like, and it provides a longer lasting effect for them.

Eric 28:11

Alex is going for his vitamin. I’m using air quotes.

Eloise 28:15

It might.

Eric 28:18

Let’s talk about that preparation. It’s because you can smoke it, you can use vaporizers, you can use gummies. David, you talked about, you tasted a beer and tea that had cannabis in it, and there’s differences. Right? Like, some of them give you more of immediate effect, some of them a more prolonged delayed effect, which also potentially changes how we think about kind of the euphoric symptoms. How do you think about all these different preparations? I’m going to turn to you, Eloise.

Eloise 28:55

Yeah, I think it depends when we’re doing our initial intake and assessment on a patient. In a lot of the nausea and vomiting cases, I will often try to do a transdermal patch. If they’re reticent to inhale for any reason, the tinctures, the drops, oil drops, can often have a strong smell and taste, and so they might have want to avoid those because it can make them vomit or make them more nauseous. And there are suppositories out there, too, although they tend to be expensive and a little bit more invasive than most people want to go.

Eric 29:30

Do you ever recommend smoking or vaporizing?

Eloise 29:34

I do, yeah. I think that there’s, you know, there’s short term benefit. So if it’s a. If it’s an acute issue that we’re trying to resolve, then inhalation, you know.

Eric 29:44

Might make sense generally through vaporizing, because I always worry about burning plant matter, and inhaling it can’t be good for the lungs.

Eloise 29:56

They’ve actually done quite a bit of studies looking at inhaling cannabis through a joint. It does show long term it can cause airway inflammation and chronic bronchitis, but short term benefits show that it can actually open up the airways. Again. There might be some benefit over risk initially, but you’re right, you are burning it to the point of combustion. You’re producing tars and carcinogens, and it can certainly irritate the throat and the lungs. So if they have mucositis or radiation, they’re not going to be a good candidate.

Vaporization is hard because most of the products on the market here in California are called vape pens or wax pens, and they’re oils that are battery operated and probably burned to the point of combustion as well. So you’re not really getting that vaporized benefit. And if you really wanted to vaporize it, you’re going to have to invest hundreds of dollars into a vaporized device and the vaporizer.

Eric 30:55

David, you did a lovely discussion about how a vaporizer works, and it depends on temperature, right?

David 31:02

Yeah, it’s basically what Eloise said, that the theory is that if cannabinoids vaporize at a lower temperature than combustion occurs, then you want to heat flower plant bud to the temperature that’s above the vaporization point, but not high enough to get matter to burn.

Eric 31:22

Yeah. And THC may be a little lower than CBD, so you can also potentially change your ratio. In theory, yeah, in theory. Okay, I got to ask about transdermal because I thought THC wasn’t significantly absorbed transdermal, and there’s questions about CBD. Thoughts on that? David, I’m going to turn to you first.

David 31:45

Yeah, I heard Eloise say that she recommends patches, so I’m going to maybe keep quiet. I mean, I love the idea of transdermals. I mean, with the caveat that some people really want, want a sense of control, and they don’t really like the idea of sticking a patch on. They want to be able to manage their own symptoms. So there’s a big aspect of patient preference there. But it’s really interesting. I mean, the lab studies I’ve seen, Eloise really make me not so optimistic that you’d actually get meaningful amounts of THC or CBD absorbed. But I mean, there are a lot of products out there and people swear by it. So tell me, what’s the truth?

Eloise 32:26

Yeah, I mean, I think definitely what I see in practice is that transdermal gives some patients more control. So there are those that are still really reticent to even try cannabis because they’re afraid of the high, right? They’re afraid they’re going to lose control or they’re going to hallucinate. If you offer them a transdermal patch, which typically can work in like 1520 minutes and last for six to 12 hours, if they’re having an unwanted effect, they can remove that patch and actually undo their experience. The only cannabis delivery method I know of where you can actually undo the potential euphoric effects in real time.

There’s really only one company out here in California that I recommend. It’s becoming really hard to find in a very adult centered market because medicinal products just don’t fly off the shelf. And they’re expensive, so it can be cost prohibitive for a lot of patients. But they’re directed to go usually on like a, on the wrist, where there’s a thinner layer of skin and the blood supply is closer to the skin or on top of the foot. So it does, you know, they obviously put chemicals in the patch to help the penetration, the permeability of the skin, and it bypasses the liver. So there’s less drug to drug interactions, there’s less intensity with the THC.

Eric 33:42

So the bypassing of the liver is important from a bioavailability standpoint. Right. The liver will chew this stuff up and youre not going to see a lot of it. Then. How do edibles and gummies work, if thats the case? David?

David 33:56

Well, yeah, you definitely lose some in the first pass effect, but its not like opioids, where that first pass effect really takes out a lot of effectiveness because the cascade of metabolism for cannabis cannabinoids is pretty complicated. And theres some metabolites that are as active as THC is the same as for CBD. So it’s maybe less of a differential, at least in my mind. But, yeah, in theory, cannabinoids like opioids, if they’re absorbed buccally, you miss that first pass effect. It feels to me like, from what I’ve seen and heard, it’s less a matter of dose.

It’s not like you lose a lot of effective dose with oral administration going through the GI tract. It’s more of a delay. And that kind of manifests as uncertainty. Like, you eat a gummy and you might start feeling something in ten minutes, it might be 40 minutes, depending on your diet and other things. And some people don’t care about that. Other people really want to know. Like, I want to know that I’m going to get some relief. I’m going to begin to feel this.

Eric 35:01

So like a vaporizer gives you more of a quicker onset. So you know what’s happening?

David 35:06

Yeah, it’s like a PCA pump. Like, you hit that button and you get a double. Now it’s the same thing.

Eloise 35:12

Yeah. It’s more predictable. It’s a little easier to control. I mean, edibles in some patients, I’ve had them report four hour delay before they feel the effects. So it’s unpredictable. And then THC gets converted into a different metabolite that’s actually much stronger than the delta nine THC. So it’s a much more intense experience, which is why people can have tachycardia and the paranoia and anxiety. And I end up in the emergency department.

Eric 35:39

And then how do you think about THC versus CBD ratios? Louise, I’m going to turn this one.

Eloise 35:46

Yeah. I really like to kind of focus on one dominant cannabinoid at a time, just so I can isolate the experience and get a sense of how they’re responding. And then maybe I’ll add in some different cannabinoids and layer them on top.

Eric 35:59

So give me an example. So do you just, like, focus on THC first or do you focus?

Eloise 36:04

Well, it depends. Yeah. So if you came to me and you had neuropathic pain, particularly, that bothered you mostly at night when you laid down, it was impacting your sleep. I would start with low doses of THC. If you came back to me and said, it’s really helping my pain, but I’m waking up and I’m feeling pretty groggy in the morning. I might add in some CBD to see if we can decrease some of that early morning groggy effect.

Eric 36:28

Yeah.

Eloise 36:29

Or I might add in CBG, which can also help a little bit with the pain and sleep, but maybe not, as, you know, intense of a euphoric effect.

Eric 36:40

And when you’re talking about low doses of THC, like, what are the doses and how are you prescribing it? Let’s say I’m coming in with neuropathic pain.

Eloise 36:49

I would first present to you what I think your options are. So it might be a topical, which we actually haven’t really even touched on. There’s. There’s some evidence that topicals can help for neuropathic pain. They work quickly. They don’t last very long. So if you’re just having a hard time falling asleep, I might say, let’s try a topical. If you’re new to cannabis, might have you get the tinctures or the drops so that we can just start with, like, half a milligram of THC and slowly ramp you up from there. It is sort of dependent on what’s in the market in the area where the patient’s at.

Alex 37:21

What about Marinol as a starting place? Do you ever go there?

Eloise 37:26

Not unless I’m totally desperate and a patient can’t afford it.

David 37:29

It’s just.

Eloise 37:33

Marinol is synthetic THC, so it’s actually a full agonist at the cannabinoid receptors, whereas plant based THC is a partial agonist. So similar to, like, buprenorphine, where it’s a partial agonist. We don’t see as many side effects. When we do with our full agonist opioids. It’s similar to plant based THC and marinol.

Alex 37:52

So with Marinol, you get too many side effects.

Eloise 37:56

You can.

Alex 37:56

You can. Yeah. That’s your major concern?

Eloise 37:59

Yeah.

David 38:00

Interaction with dronabinol usually is cleaning out the medicine cabinet. Whenever I see it on a patient’s chart, I ask whether it’s helping, and they say no. And I ask if they have side effects, and they say yes. And I ask if we should stop it. And they say no.

Eric 38:10

It’s like gabapentin.

Eloise 38:13

Yeah.

Eric 38:16

Any other pearls around dosing, David, any from your perspective?

David 38:21

I don’t think so. I think we’ve talked about some of the big ones. I mean, just to hammer home. What is a mantra for all of us, I think, is if there’s potential benefit, you don’t want to scare people away, so start low. It’s not usually something like a pain crisis where you really need to get drugs into people. Now, if you gradually ramp up over a couple of days, it’s not going to be the end of the world. So that’s often the advice I give. If somebody has a bad experience but wants to try again, I would ask them how fast they ramped up and what their initial dose was. And, you know, if it was initially a 20 milligram THC, gummy, maybe you should cut that in order first.

Eric 39:00

Or they, or they ate a brownie a half an hour later, didn’t feel anything, ate three more brownies, and then they passed out 2 hours later.

Eloise 39:10

Yeah. Yeah. For real, I would say.

Alex 39:12

Sounds like a college story.

Eric 39:13

No, there was actually in Colorado, I think there was that Atlantic article or New Yorker.

Eric 39:20

Yeah, that was a great article.

Eric 39:23

Right. As opposed to vaporizing, eating the brownie, you don’t know exactly when it’s gonna kick in.

Alex 39:29

Yeah.

Eric 39:30

And then if you don’t know, you may take it more of it because it hasn’t kicked in yet, and then you kind of overdone it. Is that right?

Eloise 39:37

Happens a lot. Yeah. I was just gonna add, with CBD dosing, I think that there’s a big misconception out there, and people actually need hundreds of milligrams to get any kind of relief on its own. If they’re really afraid of THC and they’re like, I just want CBD. They usually need hundreds of milligrams to get any relief from anxiety, sleep, or pain. So most people give up on it before they get any results.

Alex 40:04

Do you use these medications as a primary treatment or let’s say for pain, for example, which is probably the most, or maybe the most common indication? I could be wrong about that. Is it an adjunct or is it something that you’d start with?

Eloise 40:20

It’s patient preference. Often people come to cannabis when they failed everything else, so it’s usually a last resort for them.

Eric 40:29

Yeah.

Eloise 40:29

Yeah. And if nothing else is working, I did have a patient when I first started at Stanford who fired me because he was on high doses of methadone and lorazepam and, like, he had all these really heavy, you know, benzodiazepines and opioids, and he said, would you prescribe Zolpiden for sleep? And I said no, but some of my patients use THC to help them sleep. Do you want to consider that? And he said no, and then asked for a new provider, which I thought was pretty funny.

Eric 41:03

Well, so we talked about benefits. Let’s talk about potential risks. What do we know of the risks? Because, I mean, I’m just thinking back to what David was saying, that the person who felt after getting chemotherapy, he needed to smoke that joint before he got into the car to drive home. To drive home.

Alex 41:25

I believe that was the phrase. Oh, yeah.

Eric 41:27

Not to have somebody drive him, but to drive home. What do we know about the side effects, including cognitive side effects, of these drugs?

David 41:34

Yeah, we can get the obvious ones first. So driving, operating heavy machinery, not really a good idea. When I was working on stone, actually, one of my patients who’s at the VA, had bad neuropathic pain, and he was telling me that he used cannabis in the morning. He also told me that he took his kids to school and I put two and two together. And so we went to this deserted parking lot and he fired up a joint. And then I laid out this obstacle course.

Eric 42:03

Obstacle course of bananas, by the way, because.

David 42:06

And he just. Many, many bananas died that day. That was kind of a learning intervention for him, showing that it does affect so driving, for sure. Although it’s interesting, maybe I’ll make this point and then we can. Eloise and I can trade back and forth. But the interesting thing about cannabis and driving, to me is that people who are too stoned to drive often know they’re too stoned to drive. They have not always, but they have more insight, as opposed to people who are impaired by alcohol.

They think they’re fine and they think they’re invincible. And so people do have the ability to self regulate a little bit. There really aren’t great tests for whether you’re too impaired to drive, although there’s some that are coming online, but it’s pretty impressive. Like, people who are stoned, they drive really, really slowly or ride a bike really, really slowly. Everything seems to be coming really quickly and really have a hard time focusing on what’s important, which is keeping the car on the road. So I think that definitely is a concern.

Eric 43:07

And that’s the THC component.

David 43:09

Yeah.

Eric 43:10

And then are there longer term cognitive side effects from these drugs?

Eloise 43:15

Yeah, there’s definitely evidence that if you look at somebody who’s smoking daily, again, we don’t have good data on how quantifying those dosages or how much THC or CBD or other cannabinoids are in there. We definitely see it much more in adolescents who will demonstrate, if they’re using it daily and significant use, that it affects their overall cognitive as they get older. But they’ve also shown that if you stop and abstain from it after four weeks, there doesn’t seem to be any long term damage from it, but it’s as long as you’re using it.

David 43:52

One cool study that came out of the UK, I don’t know, like five or six years ago, that tracked people who used recreational cannabis, all different kinds, high THC, low THC, some with CBD, some without, and found that those cognitive effects that Eloise just described are attenuated in people who used THC with a lot of CBD, even after you adjust for THC dose. So that’s one study, 100 people. I wouldn’t hang too much on that, but it is possible that there’s some that what you’re actually using matters. And there may be varying cognitive effects depending on whether you’ve got CBD or other cannabinoids on board.

Eric 44:29

And Eloise, any other side effects you talk to your patients about?

Eloise 44:33

Yeah, I’m definitely cautious in anybody with a history of any cardiac history, especially if they have a new onset of AFIB, because we know that THC particularly can increase heart rate, can also cause orthostatic hypotension.

Eric 44:46

So sometimes mild increase in blood pressure, too. Is that right?

Eloise 44:51

Initially with smoking, it can cause an increase in blood pressure, but if you’re using it more consistently, it can actually lower blood pressure.

Eric 45:00

And then mental health disorders, schizophrenia, like, how do you think about that?

Eloise 45:05

I definitely worry about. It’s not my area of expertise. I usually want them to see someone who is more appropriate for them. But you really should be looking at family history, personal history. And if they have used it, do they experience paranoia or anxiety?

Eric 45:24

Yeah. And I guess one question, too, when we think about potentially using this in older populations, maybe even in those with dementia, like that THC component at Maranal, we see this, is that it can cause delirium, it can cause confusion. So kind of the opposite effect that they were looking at. How do you think about that?

Eloise 45:44

I don’t see it. We have some good studies with sativex that David mentioned earlier, which is a CBD, THC, whole plant preparation. It’s not approved in the United States, approved in like 33 other countries, and they’ve used it for the neuropsychiatric behaviors and dementia patients. Really low dose, you know, two to five milligrams. It’s not causing those issues.

Eric 46:11

David, any other thoughts?

David 46:13

I think in the secret often is with older adults, like anything else, start.

Eric 46:18

Low, go slow, go low.

David 46:20

Yeah, I think if you start with 1 THC in whatever preparation, I think you can maybe ramp that up. But from what I’ve seen and heard, I think you can avoid a lot of those side effects as long as you’re careful.

Alex 46:32

David, you mentioned at the beginning the scheduling of cannabinoids. I wonder if you want to say anything about that and where you think it needs to go in order to develop the evidence. Base for sensible prescribing.

David 46:47

Yeah. I don’t know. I mean, I’m not. I haven’t really had a hand in the. In the process of rescheduling. So everybody knows the thesis right now is that there’s interest in rescheduling cannabis. So it’s not as restrictive Loe schedule three, right? I think.

Eric 47:06

Correct.

David 47:07

Which would make it available through prescriptions and drugstores and a lot of politics, as you can imagine. And I know a lot of people inside the Beltway are trying to figure out what that looks like, I guess, from my perspective. Yeah, whatever. But I feel like. And this is why the stuff that radical is doing is so cool. It’s not like cannabis is a new drug that we really need to get clinical trials before we get it into people. We’ve got millions of people using this stuff. Why don’t we do a better job at learning from the people who are actually using it? I don’t think rescheduling is really going to significantly increase data. It’s a good idea.

Fine, whatever. But I feel like we’re really missing the boat if we’re not learning every time somebody takes a gummy for sleep or lights up a bong for chemotherapy induced nausea and vomiting, we should be learning from that. I’m not saying we don’t need randomized controlled trials, but in terms of real world evidence, there’s a lot out there that we’re just leaving on the table. So I think that really should be a priority. And I know radical is involved in doing a lot of that work. So quick shout out.

Eric 48:10

Okay, I got my last kind of lightning around question for each of you. You’ve convinced listeners that they need to learn more about cannabis, medical cannabis, not recreational, but medical. Where could they learn more about this? I’m going to do the first plug because I read a New England journal catalyst article, which I’ll include in the show notes, which was absolutely fabulous coming from Montefiore. They set up a medical cannabis clinic, has some great slides and information. So I’m going to encourage listeners to go to the show notes and look at that New England journal catalyst video. David, what would you recommend?

David 48:47

I would suggest my book, but it’s kind of out of date. I mean, the jokes are still funny, but

David 48:55

I still laugh when I read some of it, though, which is really not the question you’re asking. I don’t know. I mean, there’s so many sources out there. I think the biggest challenge is try to get it from a reliable source.

Eric 49:08

And I loved your book, too, because when you go into these, not the clinic. Well, many clinics, but to the dispensary, there’s tons of knowledge that they expound on.

David 49:21

Yeah. Some of which is correct, and much of it.

Eric 49:27

Where. Where can we get good information?

Alex 49:30

Our audience, our clinicians. So where can our clinician audience.

Eloise 49:34

I actually have a part of. Radical health is an education company that we have on demand, self paced modules for clinicians who have more interest in learning about cannabis. We go through the foundations and advanced sciences, and we look at cardiovascular disease and dementia and some other things. So we have a whole suite of education available.

Eric 49:57

Great. And we’ll have links to that in our show notes. With that, I want to be mindful of the time. I want to thank both of you for joining us. But before we end, Alex, time for a little doctor Dre chronic.

Speaker 5 50:09

I was alone, I took a ride I didn’t know what I would find now another road where maybe I can see another kind of mine now.

Eric 50:24

Then.

Alex 50:24

(singing)

Eric 51:13

Eloise David, thank you for joining us on this podcast.

Eloise 51:15

Yeah, thanks for having me.

David 51:17

You guys are awesome.

Eric 51:18

And to all of our listeners, again, check out our show notes for more information. And thank you for your continued support.

This episode is not CME eligible.