Huberman Lab - AMA #9: Kratom Risks, Does Infrared Sauna Work & Journaling Benefits

Episode Date: July 28, 2023

Welcome to a preview of the ninth Ask Me Anything (AMA) episode, part of the Huberman Lab Premium subscription. The Huberman Lab Premium subscription was launched for two main reasons. First, it was launched in order to raise support for the standard Huberman Lab podcast channel — which will continue to come out every Monday at zero-cost. Second, it was launched as a means to raise funds for important scientific research. A significant portion of proceeds from the Huberman Lab Premium subscription will fund human research (not animal models) selected by Dr. Huberman, with a dollar-for-dollar match from the Tiny Foundation. Subscribe to Huberman Lab Premium at https://hubermanlab.com/premium. Timestamps (00:00:00) Introduction (00:01:42) What Are the Short and Long-Term Effects of Taking Kratom? (00:24:12) Huberman Lab Premium In the full AMA episode, we discuss: How Does Infrared Sauna Compare to Traditional Sauna? Neurological Impact and Best Practices for Journaling for Goals, Habits and Growth Title Card Photo Credit: Mike Blabac Disclaimer

Welcome to the Uberman Lab podcast where we discuss science and science-based tools for everyday life. I'm Andrew Huberman and I'm a professor of neurobiology and Ophthalmology at Stanford School of Medicine. Today is an ask me anything episode or AMA. This is part of our premium subscriber channel. Our premium subscriber channel was started in order to provide support for the standard Huberman Lab podcast, which comes out every Monday and is available at zero cost to everybody on all standard feeds, YouTube, Apple, Spotify and elsewhere. We also started the premium channel as a way to generate support for exciting research being done at Stanford and elsewhere, research on human beings that leads to important discoveries that assist mental health, physical

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The first question is about cratum, and the question is, what are the short and long-term effects of taking cratum? For those of you that haven't heard of cratum, cratum is a substance that comes from a tree that grows naturally in Indonesia. The tree itself is called Mitragina Spiciosa, And it's been known for hundreds of years or more. We don't really know how long, but at least for a couple of hundred years, that when people chew the leaves of this tree,

they experience a mild stimulant effect. And there's also a process of extraction whereby you can take the leaves and get high concentrations of cratum that nowadays is packaged into various supplements, most often consumed in capsule form, although sometimes it's sold in raw powder form. Here's the key thing to understand about cratum. Indeed at low dosages, cratum has a mild stimulant effect.

However, at higher dosages, it has what's called an analgesic effect, that is a pain-killing effect, and it acts as a sedative. And, freedom itself acts as an opioid in the body. This is what's making freedom a very controversial topic these days. In particular, because most people have heard of the so-called opioid crisis, the opioid crisis has been a term coined to largely center around issues that have taken place in the United States, although these issues definitely extend beyond the borders of the United States. But the opioid crisis is essentially the overconsumption and widespread addiction to opioids. Opioids include things like morphine,

oxycodone, also called oxycontin, and there are other opioids similar to those compounds, all of which have the general effect of being painkillers and sedatives, and in some people, again, some people, eliciting a sense of euphoria, in particular at low to moderate dosages. However, people quickly develop a tolerance to those drugs and need to consume more and more of them in order to get the effect that they initially got from a lower dosage, and they are not just highly habit forming, they are highly addictive. And we can distinguish between habit forming and addictive by simply saying that addictive means people will continue to take something or do something despite negative consequences.

There are other relevant definitions of addiction as well. I define addiction more broadly as the progressive narrowing of the things that give you pleasure. And indeed, when people get addicted to opioids, it is a very bad picture. It often hampers many, many areas of their lives. And seriously, so the opioid crisis refers to the over prescription of opioid drugs. That's sort of what it's generally taken to mean, but it also includes accessing opioids such as morphine, oxycodone, et cetera, through gray market sources, through black market sources, and on and on. And of course, the acquisition of the drugs is just one piece.

It's also the overconsumption of those drugs, and of course, the addiction to those drugs, which has proved to be so pernicious. So what does this have to do with creatum? Cratum is also in opioid, and we'll talk about how it differs in its opioid properties from the drug side just talked about because it is different from morphine and hydrocodone, but it also has some similar properties as well. But the deal with cratum is that a good number of people out there have managed to wean themselves off opioids such as morphine and hydrocodone

through the use of cratum. And that has been used as justification for keeping cratum on the market and keeping it legal. However, and this is a very important, however, cratum itself has also proved to be not only habit forming, but addictive, especially when taken at dosages that exceed that lower dose that just generally creates a bit of stimulant to a little bit of euphoric effect. When people start taking higher dosages of cratum, it is very clear that it does become addictive and itself is very hard to come off of, so much so that people experience so called cratum withdrawal. Now the reason I mentioned that cratum has been used by a good number of people to wean themselves off

of the more potent forms of prescription opioids, is that when I solicited for questions about Cratum on social media, it was a very binary response. In fact, there was one camp, a very rabid camp that said, Cratum is terrible. I took this stuff, I got addicted, it was extremely hard to come off of. There were additional comments in there, such as as I know somebody who literally had to go to rehab because of

Cradle, who developed a bunch of other addictions because of Cradle, essentially many many responses of people who had only bad experiences with Cradle, meaning they liked it enough at first that they continue to take it and it became addictive for them or somebody that they know. However, there was another camp that was equally vocal, which kept saying, no, if one really adheres to the lower dosages of cratum, cratum itself can be a useful tool for getting off other opioids. And there were even a few bonafide medical professionals, medical doctors, that is, and I happen to know them and their reputations is quite good, who chimed in and sort of reconciled the two camps by saying,

indeed, if one can avoid taking credit them at all, you should. There is no reason to take this thing thinking that it's quote unquote good for you. You would be wise to avoid taking it because there is a high probability if you take it at a given dosage or at a dosage that is going to get your brain and body into a state of euphoria and ogegia and the sort of classic opioid effect that it's going to become habit forming or addicting for you. That said, these same medical professionals acknowledged that a fair number of people that they knew managed to get off of the more potent

forms of opioids, such as morphine, oxycodone, and so forth, using cratum. And they said, well, if it's a choice between being addicted to morphine and hydrocodone versus taking cratum and addicted to those substances and cratum somehow allowed them to taper off of those substances, that they would look more favorably upon cratum, if and only if they would also commit to progressively lowering their dose of cradum and eventually coming off of cradum. So the general takeaway from all of that is,

if you can avoid taking cradum, meaning if you haven't taken it already, don't. And that reminds me of a very important point, which a guest on the Hubertman Lab podcast, Dr. Robert Merlanka, who's a MD and PhDs, my colleague at Stanford School of Medicine is a world expert on the mechanisms underlying addiction and dopamine and drug reinforcement among many other things. What he said on the podcast is absolutely true, which is that it is impossible to get

addicted to a substance that you've never consumed. That might seem obvious, but think about that one again. It is impossible to get addicted to a substance that you've never consumed. That might seem obvious, but think about that one again. It is impossible to get addicted to a substance that you've never consumed. So I think the safest statement to make is if you have not tried cratum, you would be wise to avoid it. Because you stand a chance to become addicted to it. If however you are somebody that's addicted to other forms of opioids,

you absolutely should talk to your physician about that and how to get off of those opioids. But there is evidence that some people have used cratum to successfully wean themselves off the more potent forms of opioids that I talked about, namely morphine and hydrocodone, as well as a few others. Now, if you're somebody who already takes cratum, you need to be very thoughtful about the dosage that you take. And you also need to be thoughtful about the fact that people differ dramatically in their response to opioids.

This is also important and people do not talk about this enough. We hear, for instance, that, oh, you know, if people are taking anywhere from one to five grams, maybe one to six grams of cratum per day, that's keeping it in the dosage range for which people don't generally tend to get addicted. You'll hear things like that. And by the way, when I say one to five or one to six grams per day, I'm not talking about the individual compounds that are present in cratum. There are a couple of different plant alkaloids. I'll talk about in a moment that are present in cratum.

And these have different effects on the opioid system. So nowadays, some of the companies that sell cratum, and by the way, this is sold over the counter as a supplement. It does not require prescription to purchase, at least at this point in time in the United States. Some of these products will have a higher concentration of one or the other alkaloids within them such that you can't really compare one gram of one brand of Cradem to one gram of another brand of Cradem because they can have wildly different levels of these different alkaloids and these different alkaloids have wildly different impact on different aspects of your brain and body biology in particular how much they tend to impact the so-called

endogenous opioid system. Okay, so when we talk about dosages we have to keep this in the back of our mind and we have to keep in the back of our mind that there does seem to be a subgroup of people. We don't know how big this subgroup of people is, but we know it's not everyone, but it's somewhere between 10 and 40% of people seem to respond to opioids in a particularly potent way. They really like them.

And perhaps not surprisingly, people outside of that category don't tend to like opioids. I can certainly say that I am somebody who, when I've been prescribed things like vikadin or any other opioid post surgery for pain, I hate taking those drugs. I absolutely hate it. I'd rather deal with the pain. They make me nauseous. They make me feel terrible.

That said, I know people who love opioids. It's like a natural fit for their chemistry in the sense that it tends to evoke more euphoria. They just immediately like the feeling. Some of you may remember the episode of the Huberman Lab podcast that I did about alcohol. And there too, I discussed the fact that about 8 to 10% of people who consume alcohol get an increased dopamine response to alcohol that's not observed in other people. And that particular subgroup of people is very, very at risk for developing alcohol use disorder, sometimes called alcoholism, because they can drink in a way and they experience

a high from drinking in a way that other people simply do not experience. Now like everybody else, if they consume too much alcohol, they get drunk. So it's not about the drunk effect. It's about the dopamine and other sorts of chemicals that are released in those people in response to alcohol that other people just don't seem to experience at the same level of potency. So again, with things like cratum and the other opioids, there's a category of people and it's a much larger category of people. Again, 10 to 40 percent, we don't know exactly how many because the studies are

not really completed and there aren't enough of those studies yet, unfortunately. But when those people take an opioid, wow, wow, do they like it? And those people in particular are very much at risk for developing an addiction to opioids. And so those people especially should never, ever go near a cradum if they haven't or if they are already taking cradum. These are the people that are constantly ratcheting up their dose. These are the people that tell you, no, I'm not addicted, but if you were to say, hey, all right, well, then let's do an experiment where you don't take cradum for a week.

Those are going to be the people that are suddenly going to get anxious about the mere idea of that. I've also talked about this in reference to cannabis when I did an episode about cannabis. Again, I'm not putting a blanket statement out there about cannabis as being good or bad on that episode. I talked about the fact that cannabis does indeed have various therapeutic uses, but that there are a good number of people who rely on cannabis for anxiety control and other ways of modulating their brain chemistry and bodily chemistry such that if you were to say, hey, are you addicted to cannabis? They'd say, no, I don't have to smoke cannabis. I don't have to take my edibles. But if you were to push them a little bit and say, all right, well, then, you know, let's do an experiment where you don't consume any cannabis in any form for 10 days. They don't like the idea of that experiment at all. So much so that where they to run that

experiment, they would experience a lot of the withdrawal symptoms associated with addiction. So I can't in good faith say that cratum is safe for everybody because it is simply not. Now, is it safer than the other opioids? And if so, why? Well, in order to address that, let's take a short glance at the pharmacology of cratum and how it works in terms of its neurochemistry in the body. And I'm going to keep this pretty brief because in the future, I'm going to do an extended episode all about opioids, and I will include cratum in that conversation. But just to back up a little bit and discuss what opioids are. Opioids are compounds that can activate the so-called endogenous opioid system.

All of us have within our brain and body the capacity to release our own opioids. That's right, you have opioids within your body, they are released from neurons and they bind to so-called opioid receptors. Perhaps some of you have heard of the so-called runners high. The runner's high is a euphoric state. It's a fairly mild euphoric state in most cases,

but it's a euphoric state induced by long duration effort, aka the runner's high. The runner's high is just a phrase used to explain that when we engage in long duration, repetitive action effort, the body starts releasing these endogenous opioids. They bind to receptors and they trigger things like analgesia relief from pain.

They trigger mild euphoria. They tend to change our perception of the outside world, make things look more beautiful. Shiny. They give things a little bit of a sheen. What I just described is a mild version of what people experience when they take something like morphine. When people take morphine, there's a more of a sedative effect. There's more of a euphoric effect. And there's more of a dreamlike effect. And again, it will depend on dosage, creatum, and morphine and hydrocodone all have the property of acting like the endogenous opioids.

But at much higher potency, when you bring them into your system, they cross the blood vein barrier, so they go into the brain, and they bind to a number of different opioid receptors. There's the new opioid receptor. By the way, these names all follow Greek alphabet letters. So the new opioid receptor, the Kappa opioid receptor, there are a bunch of different ones. Cratum binds preferentially to the mu opioid receptor and somewhat to the Kappa opioid receptor. There's a big misconception out there. A lot of people, especially people who are proponents of

Cratum, will say no, morphine and hydrocodome bind the mu opioid receptor, whereas Cratum binds the Kappa opioid receptor, so it's a different compound, very, very different, not true, not true. Cratum, morphine, and hydrocodone, all bind to the mu opioid receptor. And that's what's largely responsible for its opioid like effects, especially when you get the dosage up

to a level where you start getting the mild sedation, the analgesia, the pain relief, and keep in mind a lot of people are taking cratum because they want pain relief. And when that mu opioid receptor system is activated, it indirectly activates a lot of the reinforcement circuitry in the brain that relates to dopamine and serotonin. This is another area that will go into in more depth in the future, but there's been a lot of controversy people saying say, Oh, you know, creatum doesn't trigger the dopamine system. Therefore, it's not addictive. But that is simply not true.

It indirectly activates the reinforcement circuitry. That includes both dopamine and serotonin, but its primary effect is to hit this mu opioid receptor system that exists in a bunch of places in the brain, but mainly in the brainstem and a structure called the peri-aquaductal gray nucleus, which then provides pain relief. It triggers a number of different shifts in cognition. It's what creates that mild euphoria, et cetera, et cetera. Now, how can we be so confident that cratum is acting so similarly to hydrocodone and

to morphine, albeit with lower potency? And the reason is, if you give people a drug that blocks the muopiod receptor prior to them taking cratum, they don't experience any of the classic effects of taking credit. No euphoria, no analgesia, no sedation, even at the low dosage is no mild stimulant effect. So we really have to look at credit as an opioid. Okay, that's just the honest truth. And if you're somebody who doesn't like this message because you like credit, I'm I'm not telling you that you don't like cratum. I'm telling you, you likely like cratum because it's an opioid. So again, if you go online and you start asking

questions about cratum, again, you're going to see these two camps. You're going to see the cratum is terrible. It's addictive. It's everything bad camp. And then you're going to see the other camp out there. very vocal as well talking about how cratum helped them avoid other things that are worse. And you know, this is an argument that frankly, I don't think we want to lean on, right? The idea that substance A is not as bad as substance B and that making substance A unavailable is just going to send everyone running for substance B. You know, that's a weak argument, frankly, right? I heard this argument around cannabis, and by the way, I'm, I think pretty balanced about

cannabis. If you listen to the episode I did on cannabis, I think you'll agree that I believe that cannabis has its therapeutic applications. I also believe that young people, especially young males with a predisposition to psychosis, should not be taking high concentration THC cannabis, because the data tell us they are already at risk of psychosis, and they are at a much greater risk of psychosis if they do. So I think I'm pretty balanced about the story on cannabis, but I often hear the argument,

oh, cannabis isn't as bad as alcohol, and therefore cannabis is good. That's simply not rational. What we should be saying is whether or not it's cannabis or alcohol or creatum or any substance for that matter. What are the potential benefits? What are the potential risks? And again, this is far too much that we can go into in this AMA and we will go into in a future full length episode of the Human Lab podcast.

But the other thing to really keep in mind is the lack of regulation over-cratum supplements. Now, as many of you know, I am a fan of many not all, but many supplements in certain conditions. I always say behaviors first, then nutrition, then if and only if it's needed, rely on supplementation. But supplementation is a big category. But when we're talking about supplements that are opioid compounds, I start to get nervous because of the high abuse potential and the high addiction potential of opioids. And cratum is included in that category.

A couple of other key notes about cratum, while death directly from cratum is fairly rare, it has happened. Now hydrocodone and morphine suppress respiration. Actually suppress breathing by way of a mechanism that if you're a listener of the Hibramin lab podcast, you know about, which is the so-called physiological sigh. Many of you, if you heard me talk about the physiological sigh, is something that you do voluntarily, the double inhale through the nose, and then a long exhale in order to rapidly reduce your level of stress, as far as we know, that's the fastest way to deliberately lower your level of stress.

But the physiological side was discovered in the 1930s as a spontaneous pattern of breathing that occurs involuntarily in sleep in order to re-inflate the lungs and offload carbon dioxide and bring oxygen back into the system on the subsequent breath. When I interviewed Dr. Jack Feldman, who is a professor at University of California, Los Angeles, and really the pioneer of the modern neuroscience understanding of respiration, he talked about some studies in his laboratory that were exploring why people die when taking opioids. This is a major issue associated with the opioid crisis.

What he mentioned was that the opioids bind to particular receptors in the brainstem locations that generate physiological size. So opioids, when taken as drugs, suppress physiological sign and do so during sleep and lack of adequate respiration, meaning people stop breathing during sleep, is one of the primary reasons why people die when they take opioids. Now, creatum is not known to suppress respiration when taken at low to moderate dosages, but when combined with any other opioids. And certainly when combined with alcohol, it can suppress respiration. And while the data on this are fairly scant, there is some evidence that creatum-induced death is caused by suppression of the respiration. And while the data on this are fairly scant, there is some evidence that cratum-induced death is caused by suppression of the respiration system. So again, death, due to taking cratum at the dosages that are recommended on most commercial packaging,

is fairly rare, although it has happened. It's unclear if it happened because it was taken in combination with other compounds. That seems likely, but we can't forget that a lot of people are taking credit at much higher dosages and in fact, progressively higher and higher dosages from these over the counter sources. And with increased dosage, there is, yes, an increased risk of respiratory failure. So again, all of this points to the fact that credit is simply not a benign substance. So if we're going to be very honest, the addictive potential of creatam is real. It is exacerbated for some people compared to others,

but it is real. It's very similarities to other more potent forms of opioids or what make it attractive for some people who are trying to come off those more potent form of opioids. But the goal, of course, is to completely come off all opioids. And creatum itself can be a bit of a trap. It can be a trap in the sense that people who have never taken other opioids can become addicted to creatum itself.

That is absolutely clear that can happen. It has happened in a great number of people. It's also clear that creatum can potentially be a trap. Notice, I said potentially, because if people are trying to come off other more potent forms of opioids and then they use cratum to do that and then they're ratcheting up their dosage of cratum such that they're now matching the endogenous response

to cratum in a way that doesn't really distinguish from the effects that they were getting from morphine and hydrocodone. Well, then they're just using a different getting from morphine and hydrocodone, well then they're just using a different form of morphine and hydrocodone. And I'm sure that some of you are out there saying that is ridiculous, you cannot compare the effects of cratum to the effects of hydrocodone. But the potency is about one-sixth of hydrocodone, and there are people out there who are just increasing and increasing both the dosage and modifying the type of cratum that they're taking so that they're getting the cratum that has a particularly high concentration of one of the alkaloids that hits that muopioid receptor hardest. And in doing so, sure, they're not getting the pure hydrocodone effect,

but they're getting really close. So my advice would be, if you haven't touched Cradum, don't touch it at all, ever. If you are taking Cradum, you need to take note of what we just discussed. Thank you for joining for the beginning of this Ask Me Anything episode, to hear the full episode, and to hear future episodes of these Ask Me Anything sessions,

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