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Your weekly dose of drug facts while dispelling fiction
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you're listening to locally produced programming created in KUNV Studios
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on public radio KUNV 91.5 please be advised that the voices and opinions you may hear do not necessarily represent the views of KUNV Las Vegas the University of Nevada Las Vegas or the Board of Regents of the Nevada System of Higher Education
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Welcome to another episode of The Chemical Collective.
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The Chemical Collective offers you your weekly dose of drug facts, while dispelling fiction. Today we're talking about the practice of taking the stimulant betel and some of its effects on the brain and society.
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So to start with, can you tell us what betel is and where it comes from?
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Well the interesting thing about betel is it comes from many different places. Mostly it comes from Asia, Africa, and some of the Pacific Islands. It's really popular in Papua New Guinea right now. It's part of a palm tree. So typically it's used as a nut, the areca nut, and this is what you make into what's called the quid. Traditionally it's used as a stimulant, an upper, gives you increased energy and wakefulness. It's also had a lot of reports of mood stabilization, making people feel happier. The prep is made with leaves sometimes of the betel vine, but almost always it's that areca nut and it's mixed with other things that we'll talk about to get some of the alkaloids
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out of it.
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Okay, so to clarify, a betel quid and areca nut are the same? Like, can you expand more on how betel is prepared or used to get its stimulant effects?
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Yeah, so the areca or betel nuts are used to make what is called a betel quid or lump. And so this quid is made by taking a fresh betel leaf from the tree, spreading a paste of slaked lime or tuna, which is a white paste made from powdered oyster shells or coral, on the leaf and then placing a small amount of the bettel or arachnid in the center of the leaf. And then from there the bettel leaf is folded and sometimes secured with a clove or cardamom pod to make a small packet. This quid is chewed
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or held in the mouth with the saliva and juices from the quid, often being spat out. And one of the things to think about too is it kind of comes like a coconut, again being from kind of the palm family. So the coconuts that you see in the store had a green big husk on it and really what you're trying to get at is that inner nut part and that's part of the quid and the betel all together that you're making the paste out of. Okay.
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Are there any variations or additions that could be added to the prep or is it usually made like the same way each time?
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Different regions have different additions. One thing that typically is done is that you add something that's highly basic. By basic, I mean on the pH scale. One of the most common things to add, as Haley has already said, is lime. And lime doesn't mean lime, like lime juice. Lime is like sodium hydroxide. And so this is one of the major variations in that some people use actual slake lime, some people use roasted oyster shells, and then how you put it in your mouth is kind of different. Again, Regen, some people use aniseed, cinnamon pod, cardamom pod, probably the most common is a mustard stalk or vine that is dipped into the slake lime and then made into this quid, this paste that gets chewed. Okay, so you just said
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Regen. It makes me wonder, are there region-specific ways to prepare it? Do you have examples of how betel is prepared in a different culture? Yeah, there are variations in the way betel is prepared across different regions and cultures. So in some parts of India, a variation called pan is popular, which includes additional ingredients like coconut, macuas, and saffron. And then in Indonesia, betel preparations called siri or sirame include ingredients like gamber.
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And now that, you know, we have obviously international trade and this has become very prominent like most drugs do, people are kind of shopping around. So I know that the Indian betel or quid can be sweeter. So some people prefer that and some are more pungent. So people are now kind of shopping all over to get different betel nuts.
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A big part of this show is discussing how drugs integrate with culture. And when I think about how drugs are typically taken kind of like in social settings with others, is there a rich history of this, but with betel use? Can you guys expand on maybe some of the cultural and social aspects of betel use? Betel is definitely seen as by the people that use it
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as a cultural drug in that one of the main properties people talk about is its ability to increase hospitality. So it causes social bonding, increases connections between people. It's also kind of seen as you know a wealth of status or you know some way to make your host make the person in their house feel good. So I don't know anecdotally I think of it as like somebody comes over and you cook them one of the best prime ribs ever or like a lobster tail. It's kind of seen like that. So it's a social lubricant also, right? So again, those social connections, kind of like we use alcohol in our culture. You have a couple of drinks before dinner. So highly cultural.
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Or like making a cup of tea or something. Absolutely. Okay, got it.
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What about its use as maybe traditional medicine or maybe in ceremonies? Yeah, so it's also used for medicinal purposes to treat a variety of coughs, colds, and skin diseases. So the areca nut itself has been used as a treatment for various conditions like dysentery and asthma. And so regarding traditional ceremonies and rituals, it's believed that petal has spiritual and mystical properties, and it was used in offerings to deities. Okay, so after chewing a
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bettaquid, how does it work in the brain? This is always my favorite part. I'm
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always excited once we get to the brain. So the short answer to this and something that's, you know, a common theme is it works in many different ways. So if you go online in Wikipedia, you're going to find out that it works on alkaloids. As I said in the past, that's how most drugs work. So the major psychoactive alkaloid in the Reconut is Orecoline. This seems to work mostly on a group of receptors called the muscarinic receptors. These are cholinergic muscarinic receptors. We talked about previously that there are two types of main receptors in the brain. You have that ionotropic that's fast passing ions and then you have that slower more modulatory G-protein coupled receptors. So this is part of those G-protein coupled receptors. There's a lot of evidence for Erycoline again working on the muscarinic system, but there's also a lot of proof that it works on the opioids which again are things like heroin, how they make you feel and there's also lots of GABAergic innovation. So GABA is kind of the major inhibitory neurotransmitter in the brain. So the short answer is it's kind of a dirty drug. It works on many different things and those are typically the drugs that are super addictive and people like a lot.
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So from what I'm understanding the Orecoline is a muscarinic agonist, right? So can you just expand a little bit on what that is.
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Yeah, so a muscarinic agonist is a compound or ligand or molecule which activates activity of the muscarinic acetylcholine receptor. And so once these receptors are activated, it can regulate processes like attention learning and memory. Can you explain more about these muscarinic receptors and maybe like what you were alluding to earlier, the cholinergic system?
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Yeah, so there's really two classes. There's the G-protein muscarinic and then the ligand-gated nicotinic. So a lot of people report that they take nicotine with this drug and also this drug is hitting the same kind of receptor. So there's a high concordance between taking Betel and then smoking or smoking and then taking Betel. So the cholinergic neurotransmitter is made up of two major classes of G-protein coupled muscarinic receptors. So drugs like pyrocarpines, scopolamine, these all act kind of on the exact same receptor, this G-protein muscarinic receptor.
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Are there different types of muscarinic receptors?
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Yeah, so by the use of selective, radioactively labeled agonist and antagonist substances, five subtypes of muscarinic receptors have been determined. And so these are named M1 through 5, so M1, M2, M3, so on. And M1, 3, and 5 receptors are coupled with GQ proteins, while M2 and M4 receptors are coupled with the GIO protein pathway. And this relates to their ability to transmit signals.
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Yeah, so again, remember back to that G protein couple receptor, those are type of class that when the ligand, you know, that's the active ingredient in the metal binds, something in the cell, a small protein, a signaling protein, a second messenger is kicked off. Interesting to me that there's two different types here, both the GI and GQ, that shows a gain. This is a compound that's able to affect a lot in the cellular space of the brain.
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Okay, so muscarinic acetylcholine receptors are coming more into focus, but what about some of the nicotinic acetylcholine receptors? Can you talk to that?
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Yeah, well, the first thing to do and to clarify this, again, nothing acts alone on a single receptor. So, for this BETL, it appears that it's going to favor the muscarinic receptors, but still there's going to be some activation of the nicotinic. And so, nicotinic acetylcholine receptors or receptors respond to acetylcholine when it binds, and nicotine is one of the ligands that can also bind or act as what we call an agnus to increase the effect. These are found in the central peripheral nervous system, that's to say they're everywhere. When I think about acetylcholine, I almost always think about something called the neuromuscular junction, and this is the space where your nerves touch kind of the muscles. So many of your tissues in your body use this receptors. And sorry, on that too, it's important to note that you know these drugs aren't working just on your brain. They are. You kind of have three brains. We always talk about this. You have your brain brain proper that we always talk about. Then you have your heart and then you really have your enteric system, your guts. And so it looks like these are really working on the peripheral nervous system, part of your ganglia, and they're also working on parts of your intestines to make them kind of signal and contract.
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Similar to the muscarinic, I'm curious now, do the nicotinic acetylcholine receptors also have different subtypes?
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Yeah, they do. So, in vertebrates, nicotinic receptors are broadly classified into two subtypes, so based on their primary sites of expression. And so, there's muscle subtype nicotinic receptors and neuronal type nicotinic receptors.
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And again, as Haley said, this is in vertebrates. So, we have a vertebra, we have a spinal cord, that's us. It's important to think about this because evolutionarily, most of these plants didn't make a drug that made us feel good. They made a drug for invertebrates, that's things that don't have a spine, things like insects that come along and nibble them, to again stimulate those muscles and slow it down, put them to sleep, make them feel maybe not so well, so that they wouldn't want to continue to eat the plant or in some cases, maybe in the betel nut case, because it is a seed, make the animal take this nut into its body and then transport it somewhere else so it could be planted. Kind of fascinating how plants kind of taken over both vertebrates and invertebrates to pass on their own genes. Yeah.
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Okay, so we've mentioned the receptor systems that betelquid use can activate. Can you guys just like briefly summarize kind of the sequence of events that happens beginning to end when you start to chew it to actual effects that we're going to get into. Yeah.
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So, when betel is chewed, orecoline first activates muscarinic receptors in the salivary glands, and this is the most overt indication of betel quid use. Orecoline is then absorbed through the lining of the mouth and into the bloodstream where it can cross the blood-brain barrier and enter the brain. And then once it's in the brain, orecoline acts on both types of acetylcholine receptors as well as other types dopamine, serotonin, GABA, which hopefully we can talk about more later. Yay GABA! And then activation of each of these receptors in combination appears to be related to developing, reinforcing, and habit-forming the addictive effects associated with betelquid or arecanut chewing. And then effects of Betelquid on the brain are complex and can vary depending on the individual, the dose, and other factors. So some of the effects of Betelquid on the brain include increased alertness, heightened mood, and increased cognitive performance. However, the long-term use of Betelquid can also have negative effects on the brain like addiction, cognitive impairment, and increased risk of neurodegenerative diseases. You mentioned that the activation of like salivary glands and that these cholinergic receptors are also expressed across the body. What are some examples of how Betel affects maybe specifically just the body?
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Yeah, so earlier I said, you know, it affects the parasympathetic nervous system and this is really that outside of your brain kind of part of your body. Hayley just talked about how, you know, we get this increase in salivary production again outside the body. So when we think about our ganglia, we have all these little kind of mini brains throughout our body that kind of inform what's happening at the tissue level. This is really where Betel is working. So one of the first things people report, especially first-time users, is kind of trying to get out the poison. And then, within this, you get this contraction of other tissues, and one of the tissues that contracts are the muscles in the eyes, so you get this pupillar constriction. Some people talk about their heart racing. I haven't seen any good evidence on that as far as papers, et cetera, but it kind of makes sense when you have that parasympathetic nervous system activation.
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Now I'm starting to see how that will use and impact both the brain and body, but I am really curious what are some of the positive and negative effects of chewing Betel? Yeah, so chewing Betel has been associated with both positive and negative effects on health. So some of the positive effects of Betel include alertness, improved mood, and a feeling of relaxation. And then as far as digestive aid goes, the alkaloids in betel can also help stimulate production of digestive enzymes, which aid in digestion. And then it also has anti-inflammatory properties. So some studies suggest that betel leaves have anti-inflammatory properties that may be useful in treating conditions like arthritis.
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Yeah, and I'm always kind of not intrigued, but curious when we talk about the digestive aids, because this is like eating a whole bunch of jalapenos right you can't call that a digestive aid it's going to speed things up right so again I think we need to see more research on that there are a lot of negative effects of chewing bettel the first one that I want to bring up is that it is likely one of the most addictive drugs plants on the planet so again in that nicotinic family, muscarinic receptors, nicotine is a drug that is highly, highly addictive. Hopefully, I don't have to tell people about that. This is more so. It often gets betel, this wrap, which is true that it causes all kinds of cancer. So it has carcinogenic properties, mostly on the mouth. Again, I suspect that isn't from the betel. That's probably from the slake lime. So you're putting sodium hydroxide, which we also call drain cleaner, and you're trying to do this to irritate the mucosal membrane, the membranes in your mouth, so the drug gets into the bloodstream faster. Again, with that slake lime, Papua New Guinea, where this has taken storm, there's a recent paper that came out showing that over half the people of Papua New Guinea are addicted to this and because of that this mouth cancer and tooth decay and gum disease are on the rise. So highly addictive, all kinds of other health risks. People have reported mothers that are addicted to this have lower weight babies. These are kind of indices A, that this is a potent drug and that it can be misused very easily.
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Are there any studies or any thoughts on how long the effects of Betel actually last? Yeah, so the effects of Betel can last anywhere from 30 minutes to several hours depending on the individual and the amount of time and frequency of use. So chewing Betel can produce a mild strong stimulant effect which can include feelings of euphoria, heightened alertness, increased heart rate and blood pressure, and a sense of well-being. And these effects typically begin within a few minutes of chewing and can last for one to three hours.
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Yeah, and a lot of that research that you just cited is from this Panket L paper that maybe we can put in some of the notes for the show. But the blood pressure and all this kind of comes out of that, that, you know, it's massively affecting your body and your body systems. One thing we didn't really get into, we just kind of got into a little, was, you know, how this kind of spreads. So the starting signal, obviously, is the acetylcholine and the nicotinic muscarinic receptors. But this is also acting on serotonin, dopamine and also GABA.
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Wow, I'm really curious about that. Can you speak a little bit more to what might make this drug be used recreationally and further to that where we might see that because I know earlier we touched on some of the social aspects of Betel but it's still
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being used recreationally? Yeah, it's being used recreationally a lot and I guess the easiest way to say why it's being used recreationally is that it's a potent drug and it's available. So if you look at places for instance like India where marijuana grows readily people have been using it for thousands and thousands of years. So most of the areas that we mentioned have the betel palm there. And so it's a traditional medicine, but then obviously when something's a medicine, it gets used recreationally.
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Would you say that it's as effective or as strong as other recreational drugs? Because you just briefly mentioned the potency. So I'm curious if that's something.
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Yeah, so that's a difficult thing to get into. I mean, all drugs have potency. I would say it has some mild effects compared to, say, things like cocaine or amphetamine, but much stronger than things like tobacco. That doesn't make it a better drug. That just means that the effects hit different targets.
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Okay. What makes it less potent or what does it have to do with addiction, for instance? How does addiction to betyl compare to addiction to some other stimulant or even depressants like alcohol, for instance?
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Okay.
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Yeah, so there's some evidence to suggest that betyl might be less addictive than nicotine, but it still has addictive properties and can lead to dependence with long-term use. We mentioned earlier that it contains the arachnid, which releases alkaloids that have a mild stimulant effect on the central nervous system. These alkaloids are similar to the ones found in nicotine, which is a highly addictive substance. So research has suggested that the addiction potential of betyl may be lower than that
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of nicotine is probably one of the most, if not the most addictive substances on the planet. So to say something's less than nicotine doesn't mean that it's safe, just means it's kind of in the ballpark of nicotine, but a little less.
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Very true.
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That makes me wonder about the use of Betel not only in a social setting, but maybe in an individual seeking perhaps therapy. Can Betel be used to treat things like depression or addiction?
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Well, people are self-medicating with this, right? And it becomes one of these again when you have a recreational drug, quandaries that we need to understand more about. So for instance, you can treat, not effectively at all, your depression with alcohol. We call that alcoholism. It's not a good thing. And it starts this vicious cycle where you're depressed, you drink. Then when you drink, you have this GABA rebound, you are more depressed, and then you drink more. So Betel's probably in that same GABA-nergic category where people are self-medicating with it, but I don't think that it's solving any problems like most drugs, right? It's probably just prolonging the issues that need to be dealt with at the time, whether they be biological or physical, psychosocial.
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Okay. Let's circle back real quick to Bettle's role in traditional medicine. Can you provide some examples or some scientific evidence maybe to support its efficacy?
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Yeah, so there's some anecdotal evidence supporting the use of Bettle in traditional medicine. There's limited scientific research on its efficacy. So some studies have investigated the potential health benefits of Betel, but results have been mixed and more research is needed so that we can fully determine its effectiveness. I was curious if you guys could just briefly summarize some of maybe the health risks associated with Betel use. I know that we touched on a couple already, but just like speed quick.
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Some of the repetitive things that we talked about earlier that seem to be coming up with Bettle are these oral health problems. Anytime you chew something, put it in your mouth a lot, it's not good for you. Even chewing gum causes problems. Oral health problems related to mouth cancer, gum disease, these are kind of foremost and in the forefront. The other ones are cardiovascular problems. So Bettle has been used associated with the increase of cardiovascular disease including heart attacks and strokes all kinds of digestive problems problems with it creating Ulcers in the gut. I don't know again if this is betel and we're putting this wrap on betel It could be more to do with again that sodium hydroxide that lime that we're putting on addiction addiction. This is for surely one. These receptors are known to be highly addictive and Betel contains all kinds of substances that we've previously known are addictive. So whether this addiction is fully just physical or psychological, we're not sure yet, but definitely it has this addictive problems. We just glossed over earlier, one of the big studies again that we mentioned earlier has shown that there's all kinds of complications that come out of pregnancy, of which the biggest one is lower birth weight. So again, as I always say, a lot more research is needed, but there are a bunch of very huge caveats with this drug.
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Is Betel legal to consume in the United States or is it regulated like other substances?
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Yeah, so in the United States, Betel is not a controlled substance, but some of its components, such as the arecanut, are classified as controlled substances under the Controlled Substances Act. Arecaline, an alkaloid found in the arecanut, is listed as a Schedule IV substance. So that means that it has a low potential for abuse and a limited risk of dependence. And then the sale and...
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Which, sorry to interrupt, if you think about it, that shows us a paucity in the scheduling, right? If we've said that this can't be addictive yet, all this stuff, it's just we haven't got ahead of where the addictive natures of this drug are yet.
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Yeah. Yeah.
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And so the sale and importation of some Betel components may be restricted, but the plant itself is native to the U.S. and it's not commonly grown or sold here. Some Betel-related products, such as Betel Nut or Betel Leaf, may be imported or sold in specialty stores and it's important to note that while betel is not illegal in the sale and distribution of certain forms of betel such as betel quid are restricted in other countries due to their health risks.
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One of the countries, two countries that I always look to in drug regulation that seem to be ahead at least in my opinion, well I'll add three because I'm Canadian one is Canada Two others are Portugal Portugal has done amazing things To decriminalize certain drugs and in that has kind of helped a lot of the problems with addiction Another one is Thailand Thailand has really jumped on board with plant medicines and Thailand has said with metal. This is a bad drug So that's something to think about too when we look at what countries have you know classified it as a controlled substance.
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Yeah, that was definitely going to be my follow-up question with other countries. Thank you for touching on that. But it does look like we do still have a little bit of time to answer some questions that we receive from students here at UNLV, specifically regarding Betel. You guys ready?
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Yes.
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OK.
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The first one is, is it possible to overdose using Betel?
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Yeah, absolutely. So when I think about overdose, the first thing I think about is something called an LD50. LD50 is the lethal dose that 50% of the, in many cases, lab animals you would have would have serious problems with it. It does have a significant LD50, meaning you absolutely can overdose on Betel. Overdosing looks like having nausea, vomiting, dizzy, confusion, and then this leads to typically some very big seizures and then even coma. And again, if you're not hitting the dose high enough to overdose, which I hope nobody ever does, having a significant dose over time can also cause problems leading to death very quickly.
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Okay, this next question looks pretty interesting too. What are the economic implications of trading betel and how does it impact the communities where it is grown and consumed?
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Yeah, so betel trade has significant economic implications for community where it's grown and consumed and so some of those implications are employment, betel cultivation and processing provide employment for many people, particularly in rural areas and this can contribute to local economies and improve livelihoods.
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Wow. Okay. Thank you guys so much. It looks like that's all the time that we have today. But thank you for the great discussion.
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Thank you, and thank you for listening to Chemical Lackadaise, where you get your weekly dose of drug facts while dispelling the fiction. Thank you, and thank you for listening to Chemical Lackadaise, where you get your weekly dose of drug facts while dispelling the fiction.
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I'm out.