How Marijuana Affects the Brain & Body | Dr. Andrew Huberman

ANDREW HUBERMAN: Now, let's take a step back into the real world and evaluate or think about what happens when someone smokes cannabis or ingests cannabis in the form of an edible or a tincture or something like that. Cannabis enters the bloodstream very quickly. In fact, within 30 seconds, it will enter the

brain

and spread throughout the

brain

and

body

. That's very, very fast. I mean, if we compare it to something like alcohol or even nicotine, depending on how the nicotine is administered, it is a very rapid administration of the psychoactive and biologically active compound, which, in this case, is THC and CBD, and probably some other things too.

Thus, in 30 seconds it reaches the brain and

body

tissues. And within 30 to 60 minutes, it will reach its maximum concentrations and have its maximum biological effects. They aren't always the same, but in the case of cannabis (and again here, I'm using cannabis as a sort of general term for THC and CBD) the effects will peak between 30 and 60 minutes. after introducing those compounds into the body in one way or another. And the effects tend to last between three and four hours, although there is some variation depending on individual metabolism, whether or not someone is familiar with the compound, believe it or not, psychologically familiar, but also biologically familiar, or yes or no .

It is not the first use or occasional use, etc. THC, CBD and other components of cannabis are highly lipophilic. That is, they have affinity and, in fact, can pass through fatty tissues. Now every cell in your body, but especially neurons, has a double layer of fat on the outside. And of course, when people hear about fat, they always think, oh, fat is bad, fats whatever. Most of the world seems to want to lose fat or body fat. Here, we are talking about the fatty membrane, the barrier that surrounds each tissue. In this case, we are talking particularly about neurons.

And THC, CBD, and the other components of cannabis are highly lipophilic, so they can penetrate virtually all cells simply by flowing into them. They also stay in those cells for a long time. So I know that a number of people, depending on whether or not they test for work, or for sport, or for cannabis, or CBD and THC, don't take this as a strict number, but normally, yes one ingests CBD or THC, smokes cannabis, ingests it orally, etc., it doesn't matter, it will remain in that adipose tissue and can be detected for at least 80 days after ingestion.

And there's a whole industry on how to expedite authorization. And I should just tell you that simply losing body fat is not going to get rid of it from your system, maybe partially in those fat cells, but certainly in the visceral fat and other fatty tissues that are in and around the brain and the body, it will get rid of it. harbor that THC molecule and the CBD molecule for quite a long time, at least 80 days. So if someone smokes cannabis or ingests it, it reaches the bloodstream very quickly. And the components that are psychoactive enter the bloodstream and can immediately access neurons and other cells and begin to have these effects of parking on those endogenous cannabinoid receptors and impacting the signaling between neurons, which leads to the subjective effects of cannabis. , including THC and CBD.

So let's talk about what those different subjective effects are. Again, this will vary depending on whether or not people are digesting cannabis sativa strains. Just to remind you, these tend to be elevated mood, alertness, and talkativeness. People who take sativa strains tend to talk a lot more than they would otherwise. Again, there are exceptions to this. Of course, there are exceptions. I'm sure there are people yelling, although I guess if you're quiet people who don't talk much, you probably aren't yelling. Or if not, you won't do it with sativa. Intentional joke. But in any case there are exceptions, but there are also general rules.

And sativas tend to satisfy people with a high, energetic mood and, again, with their heads held high. And indica varieties tend to do the opposite, more sedating, relaxing, etc. Why the hell would they do that? Okay, well, without going into a deep dive into the different neurotransmitter systems of the brain and body, what we know for sure is that CB1 receptors are present on a huge number of different neurons in brain structures and neural circuits, so that sativa strains that act as stimulants making people feel happy because they generally tend to elevate the mood, at least in certain doses, talkative, tend to make people feel like they have interesting ideas that they might want to share , they tend to limit their context so it tends to increase focus.

This is something that is not often talked about in cannabis, but it can, especially sativa strains, increase people's level of concentration on particular things. Something they are watching, something they are doing, or music, allows them to limit their sense of concentration. This will occur through the activation of CB1 receptors in the so-called prefrontal cortex, which is located just behind the forehead. And the prefrontal cortex acts as a strong modulator of the so-called limbic circuits and other circuits that are more stress-oriented. The way to think about stress in limbic circuits like the amygdala, which many people have heard of, is that they are not actually circuits for fear and stress.

There are circuits that constantly evaluate one's own internal state, heart rate, etc., and what is happening externally. And I'm sorry to say it, but the default of those systems is to detect danger, the threat detection systems. And then the prefrontal cortex largely acts as a brake on those systems, like reins pulling back a steed that would otherwise simply take off. For this reason, sativa varieties tend to increase CB1 activation in the prefrontal cortex and other circuits. This then leads to an overall reduction in stress due to the way prefrontal circuits can reduce amygdala activation. That, of course, doesn't explain why some people get very stressed and very paranoid when smoking sativa or other cannabis strains, or ingesting other cannabis strains.

We will talk about the paranoid effect and why it occurs and who could predict what would happen to them in a moment. But I just want to give you an idea of ​​how this works because, as I mentioned before, THC and/or CBD will bind to that CB1 receptor. Let's say in the prefrontal cortex, the prefrontal cortex neurons will bind there and then there will be retrograde signaling to the presynaptic neuron. And in the case of the prefrontal cortex, what's happening is that it increases transmission, increasing the release of neurotransmitters in the prefrontal cortex. However, at the same time, the same THC and CBD that are introduced into the system bind to the same type of receptors, CB1 receptors, in other brain structures, such as the amygdala.

And it causes retrograde signals to the presynaptic neurons in the amygdala, but silences the activation of those neurons. So this is interesting. We have the same compounds, THC and/or CBD, introduced into the body and brain, binding to the same receptors, in this case, the CB1 receptors, but depending on where those receptors are located and what areas of the brain we are referring to, or They are causing elevated levels of alertness and activation of systems that are designed to make you talk, be alert, be in the mood, etc., concentrate, or they are causing suppression of those circuits.

So here we have a see-saw effect where the same compound increases mood, alertness, and concentration in the prefrontal cortex, and decreases stress and threat detection in the amygdala. And that's one of the reasons why, especially sativa strains of cannabis, they allow people to get into these states of focus, some would even say flow. Although I don't want to go into what flow states really are. That's for a different discussion and is very ill-defined as it is. And I certainly don't want to give people the impression that cannabis increases flow states, because that's not always the case.

And certainly, most of the time, it won't be like that. But the idea here is that this molecule enters our brain and is changing everything towards a state of concentration, of elevated mood, of greater sense of importance about whatever we are doing. And now, of course, anything we could be doing could be writing a song, writing poetry, communicating with someone. But it could also be something as trivial as watching a cartoon or watching a movie, which is not trivial in itself but in terms of thinking about the creative aspects or the creative activity that stimulates the non-productivity-oriented aspects of cannabis.

So narrowed focus, elevated mood, more relaxed and yet energetic. Those are the main effects of sativa strains, except... and this is in very large bold, triple underlined except... except in some individuals, depending on the dosage but also on pre-existing neural circuits and propensity for anxiety , some people ingest or smoke sativa. varieties, and regardless of whether or not it is a type I, type II or type III variety. Well, regardless of the ratio of THC to CBD, people will experience intense anxiety and paranoia. Now, how can you predict who will experience intense anxiety and paranoia and who will experience intense relaxation, concentration and sense of creativity when ingesting or smoking a type I, type II or type III sativa?

Well, there's no way to predict that. And there is a lot of what I would call street knowledge, or bedroom knowledge, or peer knowledge... not peer reviewed but peer discussed, that is, among friends, people and acquaintances, what one needs to do is just smoke more or simply ingest more. You hear that, oh well listen, if it makes you paranoid, you just need to use more. This is absolutely categorically false. All we know about the way THC and CBD work is that they tend to potentiate, that is, increase the effects of these different systems at certain synapses and in different areas of the brain and body.

That is, if someone experiences paranoia or anxiety about a particular strain of the

marijuana

plant, or about eating an edible in a particular way, or a particular type of edible, it is very likely that that person will experience the same effect every time they eat it. that strain. or variety. This is part of what led to this huge industry. I mean, there are a number of different reasons, but this is part of what has led to this huge, highly personalized cannabis industry, where people spend some time really looking into the different strains of cannabis and cannabis hybrids that work best for and work best. for them in particular contexts.

I wish I could tell you that if you are a person who is between 5 feet 7 and 6 feet tall and have blue eyes or brown eyes, sativa strains will be right for you, or that sativa strains are going to give you panic attacks, I can't to do that. The only way to determine that would be to actually experience ingesting or smoking them, which is certainly not what I'm suggesting either. That depends on you. I'm not telling you what to do or what not to do, but there are no good predictors. In fact, if you look at the literature, it's not entirely clear that people who have a higher level of anxiety when not smoking cannabis experience cannabis as less paranoid or more relaxing.

That's simply not the case. Now, what we can say for sure is that general categories of effects, such as increased concentration and reduced anxiety, are largely due to the activation of areas such as the prefrontal cortex. Now, unlike other compounds like nicotine, or alcohol, or neurotransmitter systems like dopamine, when we talk about the cannabinoid system, and I say effects, biological effects, psychoactive effects, I want you to always keep in mind, please, for Please, Please keep in mind that those effects can be varied and often in opposite directions. So let's give an example of that. I just mentioned that when people smoke or eat sativa, it tends to produce a specific set of effects, or it generally leads to a specific set of effects, increased concentration, mood, etcetera.

Whereas when you ingest or smoke indica and its components, well, again, we're still talking about THC and CBD in varying proportions. But now cannabis indicates and we say, well, why would sleep transition time improve? Or at least give people the impression that the transition time to sleep improved? We'll talk later about what indica actually does for sleep. But indica also tends to suppress the activation of the amygdala and threat detection centers in the brain. Again, it binds to the same CB1 receptors and those retrograde signaling mechanisms we talked about before, but it also tends to deactivate the hippocampus, an area of ​​the brain associated with memory, which is why indica strains lead to pronounced ...or should we say deep flawsin short-term memory and sometimes also in long-term memory if consumed over long periods of time.

We will talk about consumption in the short, medium and long term, and occasional consumption in the future. So what I would like you to learn from this component of the discussion is, first of all, the mechanism of action by which cannabis impacts the brain and the body, but in particular the brain will be through the CB1 receptors. And those CB1 receptors can lead to an acceleration or a brake on particular biological mechanisms. And there will be a constellation of different speeding up and slowing down of different neural systems in the brain and body depending on whether or not people ingest sativa, indica or some hybrid strain.

And perhaps most importantly, even if you didn't understand anything I said about the biology of these different strains and receptors, understand that there is no way to predict what the effect of a given strain will be on an individual. Whether people who are considered calmer, more anxious, or having any number of different personality dimensions will respond one way or another has been extensively explored. But in fact, there is no way to know. On top of that, the dosing of THC and CBD can be quite simple in the form of edibles because there can be, at least if it's a controlled source, a defined amount of milligrams of THC, a defined amount of milligrams of CBD.

This is true for ingestibles. It's much more difficult to measure that from smokable forms of cannabis, especially if those smokable forms of cannabis are obtained through sources where there isn't a lot of clear information about the total amount of THC in that product. Now, all of this is changing quite a bit today due to the marketing of THC and CBD and cannabis products in different areas, including the United States. But still, many people ingest cannabis, THC and CBD through sources where they do not really know how much they are putting into their body. Therefore, it is very difficult to predict whether or not someone gets incredible anxiety relief, a greater sense of mood, focus and well-being, pain relief, etc., or whether or not they have full-blown panic attacks, etc. based solely on dosage information. .

Now, of course, we can create broad categories, and we're going to talk about studies that create broad categories of low dose, moderate dose, and high dose, frequent use, and infrequent use. But unlike alcohol, unlike nicotine, we can't really point to the specificity of X amount of grams of alcohol per week, that is, for X amount of alcohol, which is not certain. So I know a lot of people are wondering: how often can they smoke cannabis or how often can they safely eat cannabis, THC or CBD, in any of their different forms and products? Well, we have to really define what safety means, and we have to really recognize that there is a fairly loose set of controls over what you put into your brain and body when you ingest THC and CBD.

But even under conditions where it's very controlled, it's very difficult to predict what those effects will be. So before we get into the details of whether or not to take cannabis, who should and shouldn't, what the medicinal purposes are, and what some of the most recent and interesting data points to, I just want to briefly make a list. And I promise very briefly. I know I'm not usually concise, but I try to be thorough for your sake. I want to make a very short list of the different areas of the brain that are affected by THC and CBD, and why THC and CBD have the various effects that they do.

When someone smokes or ingests cannabis, no matter what the ratio of THC or CBD, if they experience memory deficits, and that is almost always present, it will be due to reductions in electrical activity within this region of the brain we call the hippocampus. . Hippocampus means seahorse. It is shaped like a seahorse. Anatomists like to name things based on their appearance. But in the hippocampus memory is reduced, particularly short-term memory. This is true regardless of whether or not a sativa, indica, or hybrid is used. In general, sativa strains will activate the prefrontal cortex, which will increase thinking and limit concentration on some activity.

And that is most commonly associated with sativa strains. Indica strains, as I mentioned before, tend to cause a suppression of activity in the prefrontal cortex, believe it or not. And stop thinking and planning. This is why indica strains are often used to relax and promote sleep. Regardless of whether it is a sativa or indica strain, and again, regardless of the ratio of THC to CBD, there is a general suppression of the neural circuits within the so-called basal ganglia and cerebellum. The basal ganglia and the cerebellum are areas of the brain that participate in action planning and action retention, so the basal ganglia would be the so-called go-no-go circuits.

And the cerebellum, which participates in balance but also in motor planning and sequencing. This is why people who smoke

marijuana

, regardless of the strain, will tend to have less physical mobility. Other common effects are redness of the eyes and dry mouth. This is actually due to the same general mechanism, which is a reduction in saliva and tear secretion and lubrication of the eyes by the tear glands of the eyes due to the presence of mainly CB2 but also CB1 receptors in the mouth and in the mouth. eyes. And there tends to be, especially with certain varieties of cannabis, an increase in appetite, the so-called munchies.

And that has a lot to do with a very, very high density of CB1 receptors in the hypothalamus, and in particular, areas of the hypothalamus like the arcuate nucleus of the hypothalamus, other areas as well, of course, that have tons of CB1 receptors attached. THC and CBD activate neurons that strongly stimulate appetite through two mechanisms. One is a cognitive mechanism that creates a preoccupation with food and an anticipation of taste, as well as the experience of taste. So the focus comes down to what you want to go eat. You really crave pizza. They seem to be foods rich in fat and carbohydrates.

But you really crave pizza and narrow your attention so you don't think about anything else. But it also sends signals from the hypothalamus to the intestine to neurons inside the stomach that regulate blood sugar. Therefore, THC and CBD have strong effects on blood sugar that generally lead to increased appetite. So two parallel mechanisms. One inside the brain, another inside the body, increasing appetite. And so there are a variety of different effects. And as I mentioned before, CB1 receptors are present throughout the nervous system of the brain, the spinal cord. In fact, the presence of CB1 receptors in the spinal cord largely explains the fact that THC and CBD, to some extent, although not very well studied, can provide some pain relief.

I should say something because many people perceive or believe they experience greater pain relief from cannabis than they actually do. In reality, it has a lot to do with a change in perception to basically focus on other things. But there appear to be some antinociceptive, i.e. anti-pain, effects of THC cannabis, in particular. And that is exerted largely through effects on CB1 receptors in spinal cord neurons. Therefore, a wide range of effects occur regardless of the strain you consume and whether you eat or smoke cannabis or not. And the wide range of effects can be explained by the fact that retrograde signaling can lead to activation or suppression of activity in various neurons.