Welcome to the huberman live 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 this standard huberman Lab podcast which comes out every Monday and is available.
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without further Ado, let's get to answering your questions. The first question is about Kratom and the question is, what are the short and long-term effects of taking Kratom for those of you that haven't heard of Kratom create them, is a substance that comes from a tree that grows naturally in Indonesia the tree.
Self is called MIT
Regina specioza 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 Kratom 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 Kratom indeed at low dosages Kratom 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 Kratom itself acts as an opioid in the body. This is what's making Kratom a very controversial topic. These days in particular, because most people have heard of the so-called opioid crisis, the opioid crisis has been determined
Going 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 opioid 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 an addictive by simply saying that addictive means people will continue to take something
or do something
despite negative consequences. There are other relevant.
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 has a many, many areas of their lives and seriously. So so the opioid crisis refers to the over prescription of opioid Drugs. That's sort of what it is generally taken to mean but it also includes accessing opioids such as morphine. Oxycodone Etc. Through gray Market sources through black markets.
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 Kratom Kratom is also an opioid and we'll talk about how it
differs in its opioid properties, from the drugs, I just talked about because it is different from morphine and hydrocodone, but it also has some similar properties as well.
But the deal with Kratom, is that a good?
A of people out there have managed to wean themselves off, opioids, such as morphine and hydrocodone
through the use
of Kratom and that has been used as justification for keeping Kratom on the market and keeping it legal. However, and this is a very important, however, Kratom 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 little bit of you for
The effect when people start taking higher dosages of Kratom 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 Kratom withdrawal. Now the reason I mentioned that Kratom 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 Kratom on social media, it was a very binary response. In fact, there was one Camp a very rabid Camp. That's
It created was terrible. I took this stuff. I got addicted. It was extremely hard to come off of. There were additional comments and they're such as I know. Somebody who literally had to go to rehab because of Kratom who developed a bunch of other addictions. Because of Kratom essentially many, many responses of people who had only bad experiences with Kratom meaning. They liked it enough at first that they continue to take it
and it became addicted for them or somebody that they know.
However there was another camp that was equally.
Ghal which kept saying no if one really adheres to the lower dosages of Kratom Kratom itself, can be a useful tool for getting off other opioids and there were even a few bona fide medical
professionals. Medical doctors. That is, and
I happen to know them, and their reputations is quite good who chimed in and sort of reconcile the two camps by saying indeed. If one can avoid taking Kratom 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 analgesia and that sort of classic opioid effect that it's going to become habit-forming or addicting for you. That said the 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
Kratom and they said, well, if it's a choice between being addicted, to morphine and hydrocodone versus taking Kratom and addicted to those substances and Kratom somehow allowed them to taper off of those substances that they would look more favorably upon Kratom. If, and only, if they would also commit to progressively lowering their dose of Kratom and eventually coming off of Kratom. So the general take away from all of that is, if you can avoid taking Kratom meaning, if you haven't taken it already, don't, and that reminds me of a very important point.
Which a guest on the huberman live podcast, dr. Robert Moore Lanka, who's a MD and PhD is 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.
So, I think the safest statement to make is, if you have not tried Kratom, 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 Kratom 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 crazy,
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 0. So
important, and people do not talk about this enough. We here for instance, that oh, you know, if people are taking anywhere from 1 to 5 grams, may
be 126 grams of Kratom to 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 125 or 126 grams per day, I'm not talking about
About the individual compounds that are present in Kratom. There are a couple of different plant alkaloids. I'll talk about in a moment that are present in
Kratom and these have different
effects on the opioid system. So nowadays, some of the companies that sell Kratom and by the way, this is sold over the
counter as a supplement. It does not require a 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 Kratom to one.
Ram of another brand of Kratom 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.
Not everyone, but it's somewhere between 10 and 40 percent of people seem to respond to opioids in a particularly potent way. They really liked 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 Vicodin 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.
It made 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 liked the feeling. Some of you may remember the episode of the human Lab podcast that I did about
alcohol and thereto. I
discussed the fact that about eight to ten percent of people who consume alcohol
get an increased dopamine response to
alcohol. That's not observed in other people and
that particular
Group 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
Of potency. So,
again, with things like Kratom and the other opioids, there's a
category of people, and it's a much larger category of people getting 10 to 40%. 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. Oh 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 Kratom if they
Haven't or if they are already taking Kratom, these are the people that are constantly ratcheting up their dose. These are the people that tell, you know, 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 Kratom 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. And 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
Repute accuses. 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 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
That were 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 Kratom 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 Kratom and how it works in terms of its neurochemistry in the body. 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 kratom 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 runner's high, the runner's, high is a euphoric State. It's a fairly mild euphoric state.
Eight 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,
Kratom, 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-brain barrier so they go into the brain and
They bind to a number of different opioid receptors. There's the Mew opioid receptor, by the way these names all follow Greek, alphabet letters. So the Mew opioid receptor. The Kappa opioid receptor there, a bunch of different ones
Kratom binds
preferentially to the Mew 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
Kratom will say no
morphine and hydrocodone. Bind, the MU opioid receptor,
Whereas Kratom binds the
Kappa, opioid receptor. So it's a different compound. Very, very different, not true, not true,
Kratom morphine, and
hydrocodone. All bind to the Mew 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 Kratom because
they want pain relief. And when that Mew
Receptor system is
activated it in directly 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, oh
you know, create them doesn't trigger the dopamine system, therefore it's not addictive, but that is simply not true. It in directly
activates the reinforcement circuitry that includes both, dopamine and serotonin. But its primary effect is to hit this Mew. Opioid receptor system that exists in a bunch of places in the brain. But mainly in the brain,
Damn in a structure called the periaqueductal
gray nucleus which then
provides pain relief. It triggers a number of different shifts in cognition it's what creates that mild. Euphoria etc, etc. Now, how can we be so confident that Kratom 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 MU opioid receptor, prior to
them, taking Kratom, they don't
experience any of the classic effects of taking,
Item. No Euphoria no
analgesia, no sedation. Even at the low dosage is no mild. Stimulant effect. So we really have to look at Kratom as an opioid. Okay. That's just the honest truth. And if you're somebody who doesn't like this message because you like
Kratom, I'm not telling you that you don't like Kratom. I'm telling you you likely like Kratom because it's an opioid. So again if you go online and you start asking questions about Kratom again, you're going to see
these two camps, you're going to see the
Kratom is terrible. It's
- it's everything, bad camp. And then you're going to see the other camp out there very vocal as well, talking about how Kratom help 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
Oh 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.
It is about 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
Kratom where any
substance for that matter. What are the potential benefits? What are the potential risks? And again this is far too much then 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 Kratom 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 the nutrition then if and only if its 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 Kratom is included in that category. A couple of other
key notes about kratom
While death directly from Kratom 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, the huberman Lab podcast, you know, about which is the so-called
physiological. Sigh, many of you heard me talk about the physiological
sighs 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
Full 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.
And what he mentioned was that the
opioids bind to particular receptors in the brain stem locations, that generate physiological sighs. So opioids, when taken as drugs suppress physiological, sighing, 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 Kratom is
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 Kratom induced death is caused by suppression of the respiration system. So again, death due to taking Kratom at the dosages that are recommended on most commercial packaging is fairly rare, although it has happened.
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 Kratom 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 Kratom is simply not a benign substance
so if we're going to be very
honest The Addictive potential of Kratom 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. Are 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 create them 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 Kratom itself. That is absolutely clear that can happen. It has
Opened in a great number of people. It's also clear that Kratom 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 kratom to do that. And then they're ratcheting up their dosage of Kratom such that. They're now matching the endogenous response to create them 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 form of
morphine and
Codone. And I'm sure that some of you are out there saying that is ridiculous. You cannot compare the effects of Kratom 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 Kratom that they're taking so that they're getting the Kratom that has a particular Lee High concentration of one of the alkaloids that hits that Mew, opioid 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 Kratom don't touch it at all. Ever, if you are taking Kratom 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 plus to receive transcripts of them and transcripts of the human Lab podcast, standard Channel and premium tools. Not released anywhere else.
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