How Marijuana Affects the Brain & Body | Dr. Andrew Huberman
00:00:00.000 | [Silence]
00:00:02.520 | Now let's take a step back into the real world
00:00:05.080 | and evaluate or think about what happens
00:00:07.720 | when somebody smokes cannabis or ingests cannabis
00:00:12.240 | by way of edible or tincture or something of that sort.
00:00:15.000 | Cannabis is very fast to enter the bloodstream.
00:00:19.980 | In fact, within 30 seconds,
00:00:23.520 | it's going to enter the brain
00:00:24.640 | and permeate throughout the brain and body.
00:00:26.920 | That's very, very fast.
00:00:28.320 | I mean, when you contrast that with something like alcohol
00:00:30.880 | or even nicotine, depending on how the nicotine is delivered,
00:00:33.760 | that is a very fast delivery of the psychoactive
00:00:37.160 | and biologically active compound,
00:00:38.960 | which in this case is THC and CBD
00:00:41.080 | and probably some other things as well.
00:00:43.400 | So within 30 seconds,
00:00:44.520 | it reaches the brain and bodily tissues.
00:00:47.520 | And within 30 to 60 minutes,
00:00:50.760 | it's going to reach its peak concentrations
00:00:53.240 | and have its peak biological effects.
00:00:55.520 | Those aren't always the same thing,
00:00:56.560 | but in the case of cannabis,
00:00:58.240 | and again, here I'm using cannabis
00:00:59.360 | as a kind of umbrella term for THC and CBD,
00:01:02.120 | the effects are going to peak at about 30 to 60 minutes
00:01:05.280 | after bringing those compounds into the body
00:01:07.960 | in some way or another.
00:01:09.600 | And the effects tend to last
00:01:10.960 | anywhere from three to four hours,
00:01:12.560 | although there's some variation on that
00:01:14.280 | depending on individual metabolism,
00:01:16.440 | whether or not somebody is familiar with the compound,
00:01:20.920 | believe it or not, psychologically familiar,
00:01:22.360 | but also biologically familiar,
00:01:24.080 | or whether or not it's a first-time use
00:01:25.360 | or occasional use and so on.
00:01:26.760 | THC and CBD and other components of cannabis
00:01:32.240 | are highly what we call lipophilic.
00:01:34.120 | That is, they have an affinity toward
00:01:36.920 | and they can actually pass through fatty tissues.
00:01:39.060 | Now, every cell in your body,
00:01:40.160 | but especially neurons,
00:01:41.640 | have a double layer of fat on their outside.
00:01:44.560 | And of course, when people hear fat,
00:01:46.360 | they always think, "Oh, fat's bad, fat's bad."
00:01:48.680 | Most of the world seems to want to lose fat or bodily fat.
00:01:51.600 | Here, we're talking about the fatty membrane,
00:01:54.400 | the barrier around each tissue.
00:01:56.160 | In this case, we're talking particularly about neurons.
00:01:58.960 | And THC and CBD and the other components of cannabis
00:02:03.320 | are highly lipophilic.
00:02:04.640 | So they can get into essentially all cells
00:02:06.520 | just simply by flowing into them.
00:02:08.320 | They will also remain in those cells for a long time.
00:02:11.580 | So I know that a number of people,
00:02:13.880 | depending on whether or not they get tested
00:02:15.960 | for work or for sport or otherwise,
00:02:18.080 | for cannabis or CBD and THC,
00:02:20.900 | don't take this as a strict number,
00:02:23.560 | but typically if one ingests CBD or THC,
00:02:28.560 | smokes cannabis, ingests by orally, et cetera,
00:02:31.480 | it doesn't matter.
00:02:32.320 | It's going to stay in that fatty tissue
00:02:34.140 | and can be detected for at least as long as 80 days
00:02:37.520 | after ingestion.
00:02:38.360 | And there's a whole industry
00:02:39.400 | as to how to accelerate the clearance.
00:02:42.480 | And I should just tell you that just losing bodily fat
00:02:45.860 | isn't going to eliminate it from your system,
00:02:48.960 | maybe partially in those fat cells,
00:02:51.000 | but certainly intravisceral fat and other fatty tissue
00:02:55.000 | that's in and around the brain and body
00:02:56.960 | is going to harbor that THC molecule and the CBD molecule
00:03:01.280 | for quite a long while, at least 80 days.
00:03:03.640 | Okay, so if someone smokes cannabis or they ingest cannabis,
00:03:08.320 | very rapidly gets into the bloodstream
00:03:10.960 | and the components that are psychoactive
00:03:12.760 | get into the bloodstream
00:03:13.800 | and are immediately able to access neurons and other cells
00:03:18.160 | and start having these effects
00:03:19.160 | of parking at those endogenous cannabinoid receptors
00:03:21.800 | and impacting the signaling between neurons,
00:03:24.080 | which leads to the subjective effects of cannabis,
00:03:28.560 | including THC and CBD.
00:03:29.880 | So let's talk about
00:03:30.720 | what those different subjective effects are.
00:03:33.120 | Again, this is going to vary depending on whether or not
00:03:35.080 | people are ingesting sativa varieties of cannabis.
00:03:39.280 | Just to remind you, those tend to be elevated,
00:03:41.720 | mood, alertness, talkativeness.
00:03:43.560 | People who take sativa varieties tend to talk a lot more
00:03:46.320 | than they would otherwise.
00:03:47.960 | Again, there are exceptions to this.
00:03:49.400 | Of course, there are exceptions.
00:03:50.600 | I'm sure there are people out there shouting,
00:03:51.960 | although I guess if you're the quiet people
00:03:53.200 | who don't talk too much, you're probably not shouting,
00:03:55.040 | or if you're not, you're not doing on sativa.
00:03:57.480 | Joke intended, but in any event, there are exceptions,
00:04:00.520 | but there are also general rules.
00:04:02.300 | And the sativas tend to meet people sort of mood elevated,
00:04:04.640 | energetic, again, the sort of head high,
00:04:07.620 | and indica varieties tend to do the opposite,
00:04:11.080 | more of a sedative, relaxant, et cetera.
00:04:14.480 | Why and how would they do that?
00:04:16.300 | Okay, well, without going into an extensive deep dive
00:04:18.860 | into the different neurotransmitter systems
00:04:20.420 | of the brain and body, what we know for sure
00:04:23.180 | is that CB1 receptors are present on an enormous number
00:04:26.900 | of different neurons in brain structures and neural circuits
00:04:29.920 | so that the sativa varieties that act as sort of a stimulant
00:04:34.340 | making people feel happy because in general,
00:04:38.460 | they do tend to elevate mood, at least at certain dosages.
00:04:42.060 | Talkative, tend to make people feel like they have ideas
00:04:46.500 | that are interesting, that they might want to share,
00:04:49.060 | tend to narrow their context, so tend to increase focus.
00:04:51.840 | This is something that's not often discussed about cannabis,
00:04:54.020 | but it can, especially the sativa varieties
00:04:55.860 | can increase people's level of focus to particular things,
00:04:58.940 | something they're watching or something they're doing,
00:05:00.860 | or music allows them to narrow their sense of focus.
00:05:03.460 | That's going to occur by activation of CB1 receptors
00:05:07.980 | in the so-called prefrontal cortex,
00:05:09.480 | which is just behind the forehead.
00:05:11.140 | And the prefrontal cortex acts as a strong modulator
00:05:14.460 | of so-called limbic circuitry and other circuitry
00:05:17.180 | that is more stress-oriented.
00:05:19.180 | The way to think about the stress and limbic circuitry,
00:05:22.540 | such as the amygdala, which many people have heard about,
00:05:24.940 | is that they aren't really circuits for fear and stress.
00:05:27.780 | They are circuits that are constantly evaluating
00:05:29.940 | one's own internal state, heart rate, et cetera,
00:05:32.840 | and what's happening externally.
00:05:34.780 | And sorry to say, but the default of those systems
00:05:37.940 | is to detect danger, the sort of threat detection systems.
00:05:40.940 | And then the prefrontal cortex largely acts
00:05:43.080 | as a brake on those systems,
00:05:44.900 | sort of like the reins pulling back on a steed of horses
00:05:47.740 | that would otherwise just kind of take off.
00:05:50.020 | And so the sativa varieties tend to increase CB1 activation
00:05:53.860 | in the prefrontal cortex and in other circuitry
00:05:56.660 | that then leads to a kind of overall reduction in stress
00:05:59.800 | because of the way that prefrontal circuitry
00:06:01.240 | can reduce activation of the amygdala.
00:06:03.820 | Now that, of course, does not explain
00:06:06.120 | why some people become very stressed and very paranoid
00:06:09.100 | when they smoke sativa varieties or other varieties
00:06:11.900 | of cannabis or ingest other varieties of cannabis.
00:06:14.180 | We will talk about the paranoid effect
00:06:15.940 | and why that occurs and who might predict
00:06:18.860 | that would occur to them in a little bit.
00:06:21.300 | But I just want to give you a sense of how this is working
00:06:23.500 | because as I mentioned before,
00:06:25.060 | THC and/or CBD are going to bind that CB1 receptor,
00:06:29.460 | let's say in prefrontal cortex,
00:06:30.620 | the neurons of prefrontal cortex is going to bind there.
00:06:32.980 | And then there'll be a retrograde signaling
00:06:34.900 | back to the presynaptic neuron.
00:06:36.220 | And in the case of prefrontal cortex,
00:06:38.020 | what's happening is it's increasing transmission,
00:06:41.020 | increasing the release of neurotransmitter
00:06:42.700 | in prefrontal cortex.
00:06:44.300 | However, at the same time,
00:06:46.020 | the very same THC and CBD that was brought into the system
00:06:51.060 | is binding the very same type of receptors, CB1 receptors
00:06:54.660 | in other brain structures, such as the amygdala,
00:06:57.840 | and causing retrograde signaling back
00:07:00.680 | to the presynaptic neurons in the amygdala,
00:07:03.740 | but it's quieting the activation of those neurons.
00:07:07.840 | So this is interesting, right?
00:07:09.040 | We have the same compounds, THC and/or CBD,
00:07:12.820 | brought into the body and brain,
00:07:15.460 | binding the same receptors, in this case, the CB1 receptors,
00:07:19.760 | but depending on where those receptors are located
00:07:23.020 | and which brain areas we're referring to,
00:07:25.660 | they are either causing heightened levels of alertness
00:07:30.660 | and activation of systems that are designed
00:07:33.120 | to make you talkative and alertness and mood, et cetera,
00:07:35.580 | focus, or they're causing suppression of those circuitries.
00:07:40.280 | So we have kind of a seesaw effect here
00:07:42.280 | where the same compound is increasing mood and alertness
00:07:44.480 | and focus in the prefrontal cortex
00:07:45.800 | and is decreasing stress and threat detection
00:07:49.080 | in the amygdala, and that's one of the reasons why,
00:07:51.980 | especially the sativa varieties of cannabis,
00:07:54.920 | allow people to enter these states of focus.
00:07:57.360 | Some might even say flow,
00:07:58.520 | although I don't want to go into
00:08:00.380 | what flow states really are.
00:08:01.960 | That's for a different discussion,
00:08:03.760 | and it's very poorly defined as it is.
00:08:07.180 | And I certainly don't want to give people the impression
00:08:08.940 | that cannabis increases flow states,
00:08:10.640 | because that's not always the case,
00:08:13.220 | and certainly most often it's not going to be the case.
00:08:15.600 | But the idea here is that this molecule comes into our brain
00:08:19.100 | and is shifting everything towards a state of focus,
00:08:22.280 | elevated mood, of heightened sense of importance
00:08:25.500 | about whatever it is that we happen to be doing.
00:08:27.420 | And now, of course, whatever we could happen to be doing
00:08:29.980 | could be writing a song, writing poetry,
00:08:33.760 | communicating with somebody,
00:08:35.120 | but it could also be something as trivial
00:08:36.840 | as watching cartoons or watching a movie,
00:08:40.400 | which is not trivial in its own right,
00:08:42.680 | but in terms of thinking about the creative aspects
00:08:45.440 | or the creativity-stimulating aspects of cannabis,
00:08:48.800 | not sort of productivity-oriented.
00:08:51.580 | So narrowed focus, elevated mood,
00:08:53.600 | more relaxed and yet energetic.
00:08:55.800 | That's the major effects of the sativa varieties,
00:08:58.720 | except, and this is a really big, bold-faced,
00:09:01.620 | triple-underlined except,
00:09:03.500 | except in some individuals, depending on dosage,
00:09:06.900 | but also depending on pre-existing neural circuitry
00:09:10.940 | and propensity for anxiety,
00:09:12.820 | some people ingest or smoke sativa varieties.
00:09:16.580 | And regardless of whether or not it's a type 1, type 2,
00:09:18.860 | or type 3 variety, okay?
00:09:20.540 | Regardless of the ratio between THC and CBD,
00:09:23.700 | people will experience intense anxiety and paranoia.
00:09:28.500 | Now, how do you predict
00:09:30.200 | who will experience intense anxiety and paranoia
00:09:32.760 | and who will experience intense relaxation,
00:09:35.400 | focus, and sense of creativity
00:09:37.880 | from ingesting or smoking a type 1, type 2,
00:09:40.600 | or type 3 sativa?
00:09:42.520 | Well, there is no way to predict that.
00:09:45.120 | And there's a lot of kind of what I would call street lore
00:09:47.560 | or dorm room lore or kind of peer, not peer-reviewed,
00:09:52.440 | but sort of peer-discussed,
00:09:55.040 | I mean, among friends and people and acquaintances,
00:09:57.620 | lore out there that what one needs to do
00:10:00.400 | is simply smoke more, right?
00:10:02.280 | Or just ingest more, you hear that.
00:10:04.080 | Oh, well, listen, if it makes you paranoid,
00:10:05.620 | you simply need to use more.
00:10:06.920 | That is absolutely categorically false.
00:10:09.400 | Everything we know about the way that THC and CBD work
00:10:12.760 | is that they tend to potentiate,
00:10:14.620 | that is increase the effects of these different systems
00:10:19.620 | at given synapses
00:10:21.080 | and in different areas of the brain and body.
00:10:22.640 | That is, if someone experiences paranoia or anxiety
00:10:27.480 | from a given strain of the marijuana plant
00:10:31.680 | or from ingesting an edible in a particular way
00:10:33.840 | or a particular kind of edible,
00:10:35.360 | that person is very likely to experience the same effect
00:10:39.400 | every time they ingest that strain or variety.
00:10:41.960 | This is part of what's led to this enormous industry.
00:10:46.600 | I mean, there are a number of different reasons,
00:10:47.680 | but this is part of what's led to this enormous industry
00:10:49.800 | of highly customized cannabis,
00:10:53.080 | where people will spend some time
00:10:54.840 | really seeking out the different strains of cannabis
00:10:57.280 | and hybrids of cannabis that work best for them
00:11:01.560 | and work best for them in particular contexts.
00:11:04.240 | I wish I could tell you that if you are a person
00:11:07.400 | who is between five foot seven and six feet tall,
00:11:10.860 | and you have blue eyes or brown eyes,
00:11:13.980 | that the sativa varieties are going to be right for you
00:11:16.360 | or that the sativa varieties
00:11:17.640 | are going to give you panic attacks.
00:11:19.000 | I can't do that.
00:11:20.000 | The only way to determine it
00:11:21.200 | would be to actually experience ingesting those
00:11:24.120 | or smoking those,
00:11:24.960 | which is certainly also not what I'm suggesting, right?
00:11:27.020 | That's up to you.
00:11:27.860 | I'm not telling you what to do or what not to do,
00:11:29.780 | but there are no good predictors.
00:11:31.560 | In fact, if you look in the literature,
00:11:34.520 | it is not at all clear
00:11:35.680 | that people who have a heightened level of anxiety
00:11:39.020 | when they do not smoke cannabis
00:11:41.580 | will experience cannabis as less paranoia-inducing
00:11:46.580 | or more relaxing.
00:11:47.800 | That's simply not the case.
00:11:49.760 | Now, what we can say for sure
00:11:52.480 | is that general categories of effects,
00:11:55.320 | such as increased focus and reduced anxiety
00:11:58.160 | are largely due to activation of areas
00:12:00.000 | like the prefrontal cortex.
00:12:01.440 | Now, unlike other compounds like nicotine or alcohol
00:12:04.760 | or neurotransmitter systems like dopamine,
00:12:06.740 | when we talk about the cannabinoid system,
00:12:09.000 | and I say effects, biological effects, psychoactive effects,
00:12:13.540 | I want you to keep in mind always,
00:12:15.440 | please, please, please keep in mind
00:12:17.440 | that those effects can be varied
00:12:20.060 | and often opposite in direction.
00:12:23.260 | So let's just give an example of that.
00:12:25.440 | I just mentioned that when people smoke or eat sativa,
00:12:29.360 | that it tends to lead to one specific set of,
00:12:32.240 | or generally leads to one specific set of effects,
00:12:35.120 | heightened focus, mood, et cetera.
00:12:36.520 | Whereas when they ingest or smoke indica
00:12:40.200 | and its components, right?
00:12:41.900 | Again, we're still talking about THC and CBD
00:12:44.440 | in varying ratios, but now indica cannabis,
00:12:48.180 | and you say, well, why would it improve
00:12:50.800 | the transition time to sleep?
00:12:52.720 | Or at least give people the impression
00:12:54.060 | that it improved the transition time to sleep.
00:12:55.600 | We'll talk about what indica actually does for sleep
00:12:57.800 | in a little bit.
00:12:59.020 | But indica also tends to suppress activation
00:13:01.960 | of the amygdala and threat detection centers in the brain.
00:13:04.200 | Again, binding the same CB1 receptors
00:13:06.160 | and those retrograde signaling mechanisms
00:13:08.240 | I talked about before.
00:13:09.700 | But it also tends to shut down the hippocampus,
00:13:12.900 | an area of the brain associated with memory,
00:13:16.320 | which is why indica varieties lead to pronounced,
00:13:20.620 | or I should say profound defects in short-term memory
00:13:23.980 | and sometimes in long-term memory as well,
00:13:25.620 | if it's consumed over long periods of time.
00:13:28.460 | We'll talk about short, medium, and long-term consumption,
00:13:30.780 | occasional consumption going forward.
00:13:32.580 | So what I'd like you to take away
00:13:33.660 | from this component of the discussion is,
00:13:35.460 | first of all, the mechanism of action
00:13:38.500 | by which cannabis impacts the brain and body,
00:13:42.820 | but in particular, the brain is going to be
00:13:44.260 | through CB1 receptors, and those CB1 receptors
00:13:47.000 | can lead to either an acceleration or a break
00:13:49.580 | on particular biological mechanisms.
00:13:51.260 | And there are going to be a constellation
00:13:54.180 | of different accelerations and breaking
00:13:56.540 | of different neural systems in the brain and body,
00:13:59.740 | depending on whether or not people ingest sativa
00:14:02.500 | or indica or some hybrid strain.
00:14:04.940 | And perhaps most importantly,
00:14:06.440 | even if you didn't understand anything that I've said
00:14:08.180 | about the biology of these different strains
00:14:09.940 | and the receptors, please do understand
00:14:12.100 | that there is no way to predict
00:14:14.940 | what the effect of a given strain will be on an individual.
00:14:18.920 | There has been extensive exploration
00:14:21.300 | as to whether or not people who are so-called mellower
00:14:23.940 | or more anxious or any number
00:14:26.860 | of different personality dimensions will respond
00:14:29.820 | in one way or the other,
00:14:30.700 | but in fact, there is no way to tell.
00:14:33.180 | Layer on top of that, the fact that dosing THC and CBD
00:14:37.820 | can be fairly straightforward in the form of edibles,
00:14:40.700 | right, because there can be,
00:14:42.620 | at least if it's a controlled source,
00:14:44.820 | a defined number of milligrams of THC,
00:14:48.140 | a defined number of milligrams of CBD.
00:14:50.560 | That's true for ingestibles.
00:14:52.520 | It's much harder to gauge that
00:14:54.720 | from the smokable forms of cannabis,
00:14:57.140 | especially if those smokable forms of cannabis
00:14:59.040 | are obtained through sources
00:15:00.280 | where there isn't a lot of clear information
00:15:02.760 | about the total amount of THC in that product.
00:15:05.840 | Now, this is all changing quite a lot nowadays
00:15:07.840 | because of the commercialization of THC and CBD products
00:15:12.120 | and cannabis in a number of different areas,
00:15:14.120 | including in the United States.
00:15:15.800 | But still many people are ingesting cannabis, THC, CBD
00:15:19.540 | through sources where they don't really know
00:15:20.780 | how much they're bringing into their system.
00:15:22.620 | And so whether or not someone gets
00:15:25.220 | incredible anxiety relief, enhanced sense of mood and focus
00:15:29.580 | and wellbeing, pain relief, et cetera,
00:15:31.640 | or whether or not they have full-blown panic attacks,
00:15:34.220 | et cetera, is very hard to predict
00:15:37.500 | based on dosage information alone.
00:15:39.800 | Now, of course, we can create broad categories
00:15:42.300 | and we're going to talk about studies
00:15:43.500 | that create broad categories of low dose,
00:15:45.480 | moderate dose and high dose,
00:15:47.240 | frequent use and infrequent use.
00:15:49.500 | But unlike alcohol, unlike nicotine,
00:15:52.320 | we can't really point to specificity of X amount of alcohol,
00:15:57.320 | grams of alcohol per week, which is safe,
00:15:59.880 | or X amount of alcohol, which is not safe.
00:16:02.280 | And so I know a lot of people out there are wondering,
00:16:04.640 | you know, how often can they smoke cannabis
00:16:07.840 | or how often can they eat cannabis or THC or CBD
00:16:11.480 | in any number of its different forms and products safely?
00:16:15.800 | Well, we have to really define what safely means
00:16:18.340 | and we have to really acknowledge
00:16:19.820 | that there's a pretty loose set of controls
00:16:24.020 | over what one is bringing into their brain and body
00:16:27.080 | as they ingest THC and CBD.
00:16:29.780 | But even under conditions in which it's very controlled,
00:16:33.020 | it's very hard to predict what those effects will be.
00:16:35.620 | So before moving into specifics of taking cannabis
00:16:39.540 | or not taking cannabis, who should, who shouldn't,
00:16:41.340 | what the medicinal purposes are
00:16:43.760 | and what some of the newer exciting data point to,
00:16:47.160 | I just briefly want to make a list.
00:16:48.480 | And I promise very briefly, I know I'm not often concise,
00:16:51.240 | but I do try to be thorough for your sake.
00:16:53.960 | I want to make a very brief list of the different brain
00:16:57.480 | areas that are impacted by THC and CBD
00:17:01.160 | and why THC and CBD have the various effects they do.
00:17:07.500 | When somebody smokes or ingests cannabis,
00:17:11.920 | doesn't matter what the THC or CBD ratio is,
00:17:16.060 | if they experience deficits in memory,
00:17:21.320 | and that's almost always present,
00:17:23.540 | that's going to be because of reductions
00:17:26.320 | in electrical activity within this brain region
00:17:28.340 | we call the hippocampus.
00:17:29.980 | Hippocampus means seahorse, it's shaped like a seahorse.
00:17:32.160 | Anatomists like to name things after what things look like,
00:17:35.000 | but hippocampus memory is reduced
00:17:38.000 | in particular short-term memory.
00:17:39.600 | That's true regardless of whether or not
00:17:41.400 | one is using sativa, indica, or some hybrid.
00:17:45.560 | In general, the prefrontal cortex is going to be activated
00:17:51.860 | by the sativa varieties, which is going to increase thinking
00:17:54.640 | and narrowly constrain focus to some activity.
00:17:58.820 | And that's more commonly associated
00:18:00.260 | with the sativa varieties.
00:18:01.620 | The indica varieties, as I mentioned before,
00:18:03.740 | tend to lead to a suppression of activity
00:18:05.780 | in prefrontal cortex, believe it or not.
00:18:08.020 | And turn off thinking and planning,
00:18:10.220 | this is why indica varieties are often used for relaxation
00:18:14.940 | and for promoting sleep.
00:18:16.500 | Regardless of whether or not sativa or indica variety,
00:18:20.980 | and again, regardless of the ratio of THC to CBD,
00:18:25.340 | there is a general suppression of neural circuits
00:18:28.340 | within the so-called basal ganglia and cerebellum.
00:18:30.540 | Basal ganglia and cerebellum are areas of the brain
00:18:33.100 | that are involved in action planning
00:18:34.660 | and withholding action, so that would be the basal ganglia,
00:18:36.860 | so-called go/no-go circuitry.
00:18:39.380 | And the cerebellum, which is involved in balance,
00:18:41.980 | but also motor planning and motor sequencing.
00:18:44.600 | This is why people who smoke marijuana,
00:18:49.280 | regardless of the strain,
00:18:51.620 | will tend to be less physically mobile.
00:18:54.600 | Other common effects are reddening of the eyes,
00:18:57.100 | dryness of the mouth,
00:18:58.020 | that's actually caused by the same general mechanism,
00:19:00.860 | which is a reduction in the secretion of saliva
00:19:03.900 | and of sort of tears and lubrication of the eyes
00:19:07.020 | from the lacrimal glands of the eyes
00:19:08.780 | because of the presence of largely CB2,
00:19:12.360 | but also CB1 receptors in the mouth and on the eyes.
00:19:15.980 | And there tends to be,
00:19:17.940 | especially with certain strains of cannabis,
00:19:20.620 | increase in appetite, so-called munchies.
00:19:23.460 | And that has everything to do with very, very high density
00:19:28.020 | of CB1 receptors in the hypothalamus,
00:19:30.180 | and in particular areas of the hypothalamus,
00:19:31.940 | like the arcuate nucleus of the hypothalamus,
00:19:34.460 | other areas as well, of course,
00:19:36.220 | that have tons of CB1 receptors, bind THC and CBD,
00:19:41.020 | and activate the neurons that strongly stimulate appetite
00:19:44.340 | through two mechanisms.
00:19:45.860 | One is a cognitive mechanism of creating a preoccupation
00:19:49.740 | with food and anticipation of taste,
00:19:52.580 | as well as the experience of taste.
00:19:54.460 | So the narrowing of focus to what you want to go eat,
00:19:58.580 | right, you really crave, I don't know, pizza,
00:20:01.460 | it seems to be high-fat, high-carbohydrate foods,
00:20:03.260 | but really crave pizza, and narrowing of focus
00:20:08.260 | so that you're not thinking about anything else,
00:20:09.740 | but also signaling from the hypothalamus to the gut,
00:20:13.500 | to neurons within the stomach itself
00:20:15.900 | that regulate blood sugar.
00:20:17.620 | So there are strong effects on blood sugar of THC and CBD
00:20:22.420 | that generally lead to increases in appetite.
00:20:24.580 | So two parallel mechanisms, one within the brain,
00:20:27.280 | one within the body, increasing appetite.
00:20:29.340 | Okay, so there's an array of different effects.
00:20:30.920 | And as I mentioned before,
00:20:32.180 | CB1 receptors are present all over the nervous system
00:20:35.700 | in the brain, the spinal cord.
00:20:36.780 | In fact, the presence of CB1 receptors in the spinal cord
00:20:39.500 | largely explains the fact that THC and CBD to some extent,
00:20:43.660 | although it's not very well-studied,
00:20:44.940 | can provide some pain relief.
00:20:47.020 | I say some because a lot of people perceive
00:20:50.340 | or believe that they experience more pain relief
00:20:53.080 | from cannabis than they actually do.
00:20:55.260 | It actually has a lot to do with a perceptual shift
00:20:57.840 | to basically focusing on other things,
00:20:59.500 | but there does seem to be some antinosusceptive,
00:21:02.940 | meaning anti-pain effects of cannabis, THC in particular.
00:21:07.620 | And that is exerted largely through effects
00:21:09.980 | on CB1 receptors in neurons of the spinal cord.
00:21:14.280 | So a broad array of effects are taking place
00:21:16.540 | regardless of what strain you take
00:21:17.900 | and whether or not you eat the cannabis
00:21:20.100 | or you smoke the cannabis.
00:21:21.560 | And the broad array of effects can be explained
00:21:23.980 | by the fact that that retrograde signaling
00:21:25.820 | can lead to activation or suppression of activity
00:21:28.220 | in various neurons.
00:21:30.180 | (upbeat music)
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