Key points on how recreational marijuana products affect the brain and body

Host Amber Smith: Upstate Medical University in Syracuse, New York invites you to be "The Informed Patient" with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith. Recreational marijuana is now legal for adults in New York State, and a variety of cannabis products will soon be available in dispensaries. Before you start experimenting, let's understand what you might be getting into. My guest today is Dr. Hesham Masoud. He's an associate professor of neurology and neurosurgery at Upstate. He specializes in endovascular surgical neuro radiology, and he's a member of the stroke team at Upstate. Welcome back to The Informed Patient, Dr. Masoud.

Hesham Masoud, MD: Thank you. Thank you for having me.

Host Amber Smith: Let me first ask you about the basics. Cannabis contains a bunch of ingredients. The two I think we'll be focusing on are CBD and THC. Can you differentiate those for us?

Hesham Masoud, MD: Yeah. So CBD stands for cannabidiol, and THC stands for tetrahydrocannabinol. So those are the major components, like you had said, and the differences is, the CBD is non-psychoactive, and the THC is psychoactive. I'd say that that's the biggest difference between those two major ingredients in cannabis.

Host Amber Smith: What does psychoactive mean?

Hesham Masoud, MD: Essentially what it does is, cannabis, it works on these two receptors that we have called CB-1 and CB-2. And, you know, we have this indogenous, so in internal system, that we use of endo cannabinoids that utilize these receptors. But when we're using exogenous cannabinoids from a flowering product, plant, I should say, it's acting on those two receptors, and those receptors are located in areas that have to do with executive function and memory. When we say psychoactive effect, we mean essentially really applying a lot of the effect on those systems. So, you would have differences that would have to do with those realms, and specifically what they would be would be typically, some change in behavior and inhibition, disinhibition, I would say, and memory impairment.

Host Amber Smith: Is it true that different cannabis products have different amounts of CBD and / or THC?

Hesham Masoud, MD: Yes. Yes. So, cannabinoids, exogenous cannabinoids, and cannabinoids that we're getting from these plants, they have lots of ingredients that are called just sort of phyto cannabinoids. Now the most common ones are the -- you know, in terms of their frequency -- is the THC and CBD. And that relative concentration of THC versus CBD is really what's going to predict for you if you're getting more of a psychoactive component versus one that doesn't have that and has maybe the CBDs effect, which are thought to have anti-inflammatory, antioxidant effects. And so, if you're looking at the ratio between those two -- and that's essentially what they use to sort of classify the ratios. You know, they call them "chemo types," and if 1 is if you're THC rich, and all the way down to 5 is if you don't have any cannabinoids at all in it. So, it is a marker of how to sort of predict, also, the effect of the product is by paying attention to those two concentrations or the ratio, I should say, between the two.

Host Amber Smith: Are there other components of marijuana that have important effects on the body? Or is it mostly, we need to be concerned with CBD and THC?

Hesham Masoud, MD: There are over a hundred of these phytocannabinoids, which are these exogenous cannabinoids that we're getting from the flowering plants that can be extracted. But I'd say, yeah, THC and CBD are the most abundant. And so that's the focus and primary understanding of its effect and modulation. You know, CBD is interesting because it signals through different pathways and it doesn't activate CB-1 and CB-2. So that's why you don't get that psychoactive effect. So CBD is a cannabinoid that doesn't act on those two receptors, and that's why we think it doesn't have those impairments associated. And then you see its use in a broad field, almost like a cure-all. Now CBD at low concentration blocked certain receptors, and in a higher concentration may activate others. And so these are sort of the ideas of its effect, but it does not include the CB-1 and CB-2, and that's why people are not having those, behavioral disinhibition and memory loss associated.

Host Amber Smith: You specialize in taking care of patients who have had strokes. I wonder, is there an association between marijuana use and strokes?

Hesham Masoud, MD: I will say just as a blanket statement, anecdotally in my own practice, over 10 years now, I would say it's exceedingly rare that I've seen marijuana be the culprit that is directly associated with a stroke. And this seems to be born out in the literature when we're looking at population studies. And so there's a lot of differences when we're trying to interpret population studies. Cause you know, populations are a little bit different obviously. And so, there are Swedish trials out there. There are nationwide inpatient sampling that we do of different age groups. And for the most part, there is not a clear association across the board between marijuana and strokes. And so, preparing for this, I tried to pick out sort of the highest risk stuff that I've found. And then for every one that you find an association, you may find something that doesn't have that association. And so it makes it a little bit more difficult. And I think to start, it would be sort of pertinent to understand, okay, what is this doing to my risk factors for stroke in general and kind of start from there. Because I think one thing that might be lost in population studies is essentially the specificity of someone's own circumstances. That kind of gets washed out when you're looking at a large population.

So someone may have an individual risk that is maybe modulating by the THC use. So for instance, it's thought that THC may have effects on blood pressure, may have effects on heart rhythm. And so if I'm someone who's tenuous in that regard, then maybe it may tip me over into a bad state, a pathological condition, as opposed to just, oh, a symptom. That's the thing about marijuana, I would say, sort of the overarching theme.

But if we look at some of the data, the effect that marijuana has on blood pressure is typically a lowering of the blood pressure, not a highering of the blood pressure. And high blood pressure is the thing I worry about the most for strokes.

However, if you have a certain scenario where your blood vessels are narrow, and you lower your blood pressure suddenly, then maybe that narrowing and that low blood pressure can equal a stroke. So you can see how a specific scenario is lost when I make these blanket statements. So I don't want a listener to be like, "oh yeah, I listened to this, and they just said, oh, population studies." No. Well, in general, yes, it seems like the risk is lower, and really what seems to be the issue is how you're ingesting this thing. So if you're mixing it with tobacco, and tobacco inhalation and smoke is part of this, it's certainly more inflammatory an agent to your system and detrimental potentially than it would be, for instance, if you were using it in a way where you're not combusting it.

So not combusting it means vaporizing where you can pass hot air through it. Or, ingesting it, which has its own special considerations between those two, but just to kind of understand the, the risk profile. There are things about how one is using the marijuana that we're seeing. A population study will find a risk associated with marijuana and then say, oh, but if we control for smoking, that risk goes away. And then another observation that it has a synergistic effect potentially. So marijuana and smoking -- bigger risk for stroke. These are the things that I think we have to pay attention to.

Now there is a study that I found about heart attacks -- which I thought was interesting and of relevance here -- that found that within about an hour of smoking marijuana, this observation that there was an elevated, up to five times almost -- short of an, a 4.8 -- so almost five timeelevated risk of having a heart attack within an hour of smoking. So compared to a period of nonuse. And so that maybe signals that it could sort of trigger an acute illness, right? An acute condition. Does it do that for everybody? It doesn't seem like it, but when it does, it seems like there's an elevated risk in certain situations.

Now, interestingly in another study over 25 years of follows, so we're talking about around 5,000 patients followed for around 25 years, they found that marijuana wasn't associated with heart disease. So you can see how it's difficult to interpret this in a black and white fashion. Um, and that held true for other risk of death from cardiovascular disease and stroke. And then again, on the flip side, maybe an increased risk in a three-year study of cumulative incidents, which is maybe a difference of around 0.5%. So 1.37 and 0.5 4% was the difference, so you can see how these risks are not huge differences when they're being quoted or observed. And they're also not consistent. But that doesn't necessarily convey a universal low risk for everyone who's using the recreational marijuana.

You know, this is a long answer to a short question, but I think it's important that it kind of extend it out to include things that, you know, were specific to stroke risk and found that patients who had heavy use -- meaning more than 10 days out of the month -- may be at an elevated risk for TIA (trans ischemic attack) and stroke. And like I said, there might be vulnerable populations. So, you know, in one Canadian study, pregnant patients who really shouldn't be smoking marijuana, obviously, because that has a risk to the baby in certain development, but they may have even higher risk of certain types of strokes, like a bleeding stroke. So again, speaking to this, it's all a combination of its effect and how that has its unique consequences, depending on what the risk profile is, which is individual.

Host Amber Smith: So there might be a risk of, like you said, heart disease or stroke, but I'm also curious about if someone is experiencing symptoms after they've taken a cannabis product and it feels like they're having a stroke. Have you seen cases where the side effects of cannabis use, make a person feel as if they're having a stroke?

Hesham Masoud, MD: You know, this is really a great question to ask because anything that gets commercialized is automatically going to get more intense flavor, and higher effect, and more potency, right? That's essentially what happens with products that are sold in that way. And so we're seeing that. A study found that the THC component, the potency has increased from 4% in 1995 to around 15% in 2018. So it's important that we know that we're also maybe getting some more potent recreational use here. And so it is important to distinguish between the two things. So going back to what does it essentially do? So we talked about behavioral disinhibition. We talked about memory. And then, some of the cardiovascular effects which may have to do with the rhythm of the heart and lowering the blood pressure.

And so essentially what I would say is it really goes down to the symptom to me. So if someone smokes or uses marijuana and then has a prolonged palpitation of the heart, I wonder did that then precipitate this patient to going into atrial fibrillation, which is an irregular heart rhythm that may be stimulated. Now again, in the literature, is this a consistent observation? No, but it would be something that I would worry about, something that is now triggering an underlying condition, and it's come now and bubbled up to the surface. If someone is hypotensive, and they feel like they're going to pass out, and essentially they're just an overall feeling of malaise or whatever, I'd say, come in, you may need to get some fluids.

Host Amber Smith: Are there symptoms that would prompt someone, a cannabis user, to seek medical care?

Hesham Masoud, MD: So looking at symptoms that can happen from acute use of marijuana, I kind of reviewed poison center calls in Colorado, from a period of time of over a couple of years and found that the most symptoms seem to be things like being agitated or irritable, confused, and for the most part, people just got IV (intravenous) fluids when they got to the hospital, and a couple got maybe an anti-anxiety medication because they were having maybe too much anxiety related to what I would presume is a higher THC content in a specific product. Those are the kinds of things that I would expect to see. Now in my practice, have I really been called a lot for patients who've had a marijuana intoxication that have had a stroke? Only once in the emergency room. An older patient presented to me, and I examined him, and really, it's key that you don't try to make a lot of decisions on your own. Because you want an evaluation. And like I said, something like this can precipitate a real deficit. And so I would go back to the symptoms.

If the symptoms are, from a neurologic standpoint, are a subtraction of neurologic function. So suddenly I can't do something, then I want you to get evaluated. And then the evaluation is really going to be, is this something that could be attributed to a vascular territory in the brain versus just an overall drug effect? And then it's important to know, what is this person's blood pressure? What is their heart rhythm? Do I need to support that? In some very small instances -- you know, obviously children have a more sensitive; they may need to get respiratory support. There is a condition that has been linked with marijuana use that's called RCVS. Marijuana products have a vasoactive component in terms of its effect, meaning that it can exert an effect on our blood vessels in the brain, in terms of their size maybe they can spasm down as a relation tomarijuana, and that has been described in a condition called reversible cerebral vasoconstriction syndrome, (RCVS.) It's a descriptive term, which essentially means that the blood vessels of the brain, they clamp down, but it was reversible. It went away after a while. And this is linked with certain medications and has been associated with marijuana use, presumably because of this vasoactive effect of the cannabinoids. And so that's something to be aware of.

How does it manifest? Well, a sudden onset, really severe headache. And so it can mimic an aneurism rupture. And in some instances you may even see leaking of blood on the surface of the brain. Now the good news is, is the prognosis of it is very different and favorable in comparison to an aneurysm that's ruptured, but you can see how it can be a pretty seriouscondition. And so that is something that I think people should be aware of that if you do have a sudden severe onset headache, you should get that checked out.

Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith talking with Dr. Hesham Masoud. He's a neurologist at Upstate, and we've been talking about marijuana since recreational marijuana is now legal for adults in New York state.

Now, people may not want to damage their lungs by smoking. So edibles are maybe gaining favor -- gummies, chocolates, teas. Are edibles more potent in terms of THC than smoking marijuana would be?

People are more health conscious now, and this is a good thing, and so other methods of ingesting marijuana are becoming pretty common. So you had mentioned edibles. Another one is vaporizing, and that could be vaporizing the dry flower product or vaporizing a concentrate where essentially you're not combusting but using some sort of material to heat and provide air and pass it through. And it's important to know that eating versus vaporizing has a different effect, slightly, that is not as easy to predict in terms of comparing it to smoking it using a conventional lighter. And so the reason for that is because these cannabinoids, so for instance, for vaporizing, they can have different vaporizing points in terms of temperature. And therefore you can have different ratios between your THC and your CBD than if you had smoked it. And so, essentially, people have a conversion factor of say, well, you know, 0.3 of the dose smoked is the same as the dose vaporized. But you can see how there is a consideration with that.

Hesham Masoud, MD: Now the other thing about an edible to consider besides its effects, so its effect is a little bit different because it's metabolized, and when it's metabolized through the liver and in our system, it gives us a product that has maybe a little bit of a different psychoactive effect that can be a little bit more, have a slightly different flavor to it and be a little bit more potent in a way that is different than smoking it. And so that can be difficult to predict as well because the dose response has to do with, obviously, the time from ingestion, and it's not as quick an absorption as it would be if one were inhaling it through smoking or a vapor. And then it's also important to know that this THC or these cannabinoids, if you're ingesting it, are really enhanced by foods that have fat in them. And so if you eat something that's greasy, it may potentiate the effect even more. So it can be a little bit difficult with edibles. And a lot of times you'll see scenarios where, or you're hear about scenarios where people don't wait enough time to, to know what their effect is going to be. And so they keep eating a little bit more, and then it potentiates. So, I would say it's a little bit more psychoactive when it's with an edible, so it can have a slightly different almost a little bit more of a potential effect on there. And then, it's difficult for the prediction of response. I would say at least a 90-minute period, and start really slow.

Host Amber Smith: Now marijuana was used medicinally before it was legalized for recreational use. What did doctors prescribe it for?

Hesham Masoud, MD: So historically things like pain management, anxiety coming back up again. CBD is something that's being touted as an antioxidant and anti-inflammatory agent. And so people are trying to utilize it in conditions where there may be inflammatory nerve pain, or arthritic pain or so on and so forth. Other than that, there has been some business about its use in seizures. It hasn't really been born out that much in data, but that might be something that listeners may have heard about. Essentially, it's just about this THC CBD profile and that ratio and trying to figure out, well, what would be helpful if I did a lot of this, or if I had more of this in the ratio? You know, the plants are different, right? So if you were to split the two plants and say, okay, what's a plant that's going to give me more body and less of a head effect, then I would say would be something that would be indica. Indica plants sort of tend to do that sort of effect. And then a sativa is something that's going to maybe make you more anxious or have more of a psychoactive effect. And so that's a basic marker between the two. But again, it's important to note that indica will have THC in it, right? It's just about the ratios. So I think looking at those ratios, one can sort of predict where these things are being used as therapeutic agents, but, you know, clinical trials are forthcoming.

Host Amber Smith: Are there cannabis products that could be used legitimately to help with sleeping, for instance?

Hesham Masoud, MD: Well, the indica products tend to be ones that have more of a body effect that will make people sleepy. I just think essentially utilizing something like a recreational drug for a sort of basic housekeeping, sleeping, things like that, is probably not a great idea, in the same way that it would be not a great idea to be taking sleeping pills as your way to sleep because it's indicative of something else here. Why can't we sleep? Is it because of poor sleep hygiene? Is it because I have a sleep condition? You know, it's sort of a symptom and not something that needs some attention. So essentially, yeah, it would be higher up on that indica content or indica flavor, which would essentially make people more sleepy. People have used it specifically for that. But I would say in terms of medicinal use, I think it's important to understand why these things are happening to us before we start trying to figure out how to solve them.

Host Amber Smith: Are there long-term neurological effects from cannabis use?

Hesham Masoud, MD: There is a consideration about the timing of marijuana use in terms of adolescents, which can sort of put a cap on some cognitive abilities, seems to be the observation. And then it seems to be that people who have long-term use may have some structural changes on their MRI, so certain areas related to memory can be a little bit smaller. And so there is a concern that it can have long-term cognitive effects if we're using those structural changes as a surrogate for cognitive impairment. So yeah, I think it's very clearly bad for adolescents, and I think there is a suggestion that long-term -- I mean, it makes sense, you know -- if long-term, I'm using something that is inhibiting my memory center, then maybe longterm that memory center is going to be smaller than one that's not constantly being inhibited. You know what I mean? That would be, my interpretation of it as well. But in terms of, are we seeing long-term cannabis users are now going to nursing homes because of cognitive impairment? No, but there is a signal here of its effect in that direction.

Host Amber Smith: Interesting. Do you have any advice for adults who want to try cannabis products now that the state has made them legal? I'm thinking about you just mentioned two different types of plants that are grown differently that have different concentrations of CBD versus THC. How would a person know that when they go to a dispensary? If you were to enter into a dispensary and have to be tasked with making this decision, I would say 1. Be aware that you're dealing with more potent products now. So if you had used a recreational marijuana in the past, then maybe now you're entering into a commercialized space now, and so you need to be aware that things are significantly more potent. Be aware that essentially THC is what's going to have that psychoactive alkaloid that's going to have those behavioral disinhibitions, maybe anxiety, so on and so forth. That's going to be in a higher concentration in sativa plants. So if it says sativa, if it comes from a sativa plant, or they say "sativa dominant," expect that that means it's going to have more THC, so potentially more psychoactive versus CBD. And CBD is the one that has the anti-inflammatory, antioxidant effect and sort of the body type stuff. And thatmay have a higher component or higher concentration in a plant called indica. So if it says "indica dominant" or indica, then I would expect not to get as cerebral, but maybe more body. Are you never going to have the cerebral? No. Unless it's like zero THC and all CBD, expect to have some sort of psychoactive component. So that would be something to be aware of. It's this ratio though, of how much between THC and CBD and using sativa as your surrogate for THC and indica as your surrogate for CBD with the knowledge that indica still has THC in it.

Hesham Masoud, MD: I would say another thing to be aware of is the people behind the counter for the most part, if you're going to a dispensary that has some regulation to it, are going to know a little bit about things. So I would share maybe your history of use because potency is modulated, obviously, by your own intrinsic tolerance. And you can't really say, "oh, well, when I use alcohol, I am fine, so I'm going to be okay with marijuana." There is really no conversion there that I've seen. But, just sort of sharing that, "yes, I'm a heavy cannabis user," or "I'm a very light user," so on and so forth. And then that general awareness of that ratio in those two plants, I think one would do well to, as much as one can, sort of predict a little bit how things are going to go. And then when deciding on the way to ingest it, understanding that a vaporizer may be more potent, an ingestible may have a little bit more of a different behavioral effect than what you were used to when you had tried marijuana in the past. That can be in a very delayed fashion, so really give yourself time and plan your day accordingly. I think those are the basic considerations.

Host Amber Smith: Can a person predict how their body's going to react to cannabis?

Hesham Masoud, MD: Like I said, I think it really has to do with your tolerance level. And I would say it's really just about understanding when you would notice the effect. So if I've smoked within 15, 20 minutes, I sort of know what my dose was and what I would expect with, and then maybe stop, or someone wants to modulate beyond that point. But for ingestion, it's different because you may forget that you took something or time passes in a different way, and you maybe get a little bit of a psychoactive effect and then your understanding of time gets more expansive, and then you sort of forget, and then you re-dose. And so I would say maybe setting a timer for an edible so you understand when to expect, sort of an alarm like, "OK, by now it would have worked." And if it didn't, then I know where my general tolerance is.

Host Amber Smith: Do you think a person who's never tried cannabis before, will they experience symptoms the first time they try it, or is this something that you have to use over time?

Hesham Masoud, MD: It depends. I mean, the thing that's interesting is, you'll hear anecdotally, I'm sure people have conversations with friends and family members or whatever about like, oh, different tolerance levels, just inherent to the first time they tried it. "Oh, I tried it, I didn't feel anything." And so, really there's a big variable here, which is, we don't really know what we've tried, because we don't have that information. Now, with the legalization, the advantage is now I know what this stuff is, right? I know if it's sativa. I know if it's indica. I know if it has a THC component, that's higher CBD component. So I really, I can predict almost, based on my understanding of that ratio, right? And then how it's affected me specifically, I would start with a really low dose, and then wait for the effect. That's how we do it with pain medications in the hospital, interoperatively. I start with a very small dose. I see how it works. I wait enough time to expect that effect. And then I re-dose. I don't do cumulative dosing because I don't want to have a snowball effect at the end. And I think that that makes sense for anything. So yeah, the good news is, is if one has a basic understanding of the ratios, one can predict more than they could ever in the past. And I think it's important to know what we're using. There are synthetic cannabis out there, and that's dangerous and has a different effect and is very clearly linked to stroke and seizures and things, so it's important that if people are going to get these products, you get them from a very reputable source that's been verified. And I think that's an advantage behind legalization at the very least.

Host Amber Smith: If someone ingests marijuana and then starts having troubling symptoms, can they do anything to get it out of their system?

Hesham Masoud, MD: I did look into this and found for the most part, it seems to be waiting it out, having awareness that this is a drug effect in a big sense can sort of calm one down. Changing the sensory experience, so taking a shower. I would be mindful if you take a hot shower and you're having low blood pressure, then you may feel even worse and want to pass out, but maybe using something cold on the face. If you change the sensory experience, that tends to assist. Like we went over the poison control calls and when it got really bad, patients may have gotten an anti-anxiety drug in a controlled fashion in the emergency room. So what could be a search surrogate for that? Well, it seems like you can take CBD, so if you have a CBD -- no THC, just CBD -- product, apparently that might help. And then there is some interesting business about terpenes. And so I looked into this, and so terpenes are essentially like these essential oils of plants and are these aromatic, organic hydrocarbon class of these natural sort of unsaturated hydrocarbons that these plants produce. And they're classified by the number of carbons: mono, di, terpene, whatever. And the research seems to suggest that terpenes can modulate the effect of the cannabinoid at the receptor. So it can either assist its effect or inhibit its effect. And so, there are these "cure-all's," and in pop culture, I guess Neil Young is famous for recommending peppercorn if one has a little bit of an adverse effect to the recreational use, or lemon. And I think the idea here is to sort of evoke those terpenes that can inhibit the cannabinoid. And I've heard that in relation to just eating, that I'll maybe eat something, I think, oh, perhaps if they're eating something with a high terpene content.

So I think for the most part wait it out. Be aware that this is a drug effect and not something more sinister than that. If there is symptoms of actual organic disease, God forbid, like a sudden neurologic deficit, a prolonged heart rate rhythm, then come in and get it evaluated. If it's nothing, it's a quick turnaround. But be aware that maybe marijuana can be the straw that breaks the camel's back for someone specific, with a specific set of circumstances. And then, maybe take some CBD or use this terpene hypothesis.

Host Amber Smith: Well Dr. Masoud, I thank you so much for making time for this interview.

Hesham Masoud, MD: Oh my pleasure.

Host Amber Smith: My guest has been Dr. Hesham Masoud. He's an associate professor of neurology and neurosurgery at Upstate, where he specializes in endovascular surgical, neuro radiology. And he's a member of the stroke team at Upstate. The Informed Patient is a podcast covering health, science and medicine brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe. Find our archive of previous episodes at upstate.edu/informed. This is your host, Amber Smith, thanking you for listening.