The Effects of Cannabis (Marijuana) on the Brain & Body

00:00:00.000 | - Welcome to the Huberman Lab Podcast,

00:00:02.280 | where we discuss science and science-based tools

00:00:04.880 | for everyday life.

00:00:05.900 | I'm Andrew Huberman,

00:00:10.400 | and I'm a professor of neurobiology and ophthalmology

00:00:13.320 | at Stanford School of Medicine.

00:00:15.160 | Today, we are discussing cannabis,

00:00:17.120 | also referred to as marijuana.

00:00:19.480 | Cannabis includes many different compounds

00:00:21.880 | that have profound impact on the brain and body.

00:00:24.960 | So while many of you have probably heard of THC,

00:00:27.720 | there are also compounds in cannabis

00:00:29.880 | such as CBD, and of course there are different types

00:00:32.640 | or strains of cannabis, including sativa strains

00:00:35.300 | and indica strains and hybrid strains.

00:00:38.200 | And believe it or not,

00:00:39.040 | nowadays there is also an entire literature,

00:00:41.900 | meaning a scientific and medicinal literature

00:00:43.960 | about type one, type two, and type three strains.

00:00:46.160 | I'll explain what all of that is and how they work.

00:00:49.000 | I'll talk about some of the medicinal applications

00:00:51.240 | of different strains of cannabis

00:00:52.720 | and combinations of cannabis strains,

00:00:54.840 | as well as some of the potential health hazards

00:00:57.560 | of cannabis use.

00:00:59.240 | I want to emphasize that any discussion about cannabis

00:01:01.400 | has to be framed within the context

00:01:03.160 | that the legality of cannabis varies tremendously

00:01:07.000 | depending on where you are in the world.

00:01:08.460 | So depending on which country you're in

00:01:11.120 | and even which state you're in

00:01:12.440 | or which area within a country,

00:01:14.760 | possessing and using and certainly selling cannabis

00:01:17.400 | can be either highly illegal or entirely legal

00:01:20.440 | or decriminalized or largely overlooked.

00:01:23.240 | You of course are obligated to know

00:01:25.400 | what those local laws are for you,

00:01:27.760 | where you live and where you travel.

00:01:30.000 | With that said, today's discussion really will include

00:01:33.600 | a full picture as to where cannabis

00:01:37.080 | and the various and even very specific compounds

00:01:39.780 | within cannabis can be extremely useful

00:01:42.200 | in the treatment of some ailments

00:01:44.160 | and where certain compounds in cannabis

00:01:46.800 | can be extremely dangerous for certain individuals to use,

00:01:50.200 | in particular individuals that have pre-existing

00:01:53.600 | genetic propensity for psychosis.

00:01:56.180 | That theme is going to come up again and again,

00:01:57.900 | but we are also going to talk about the role of cannabis

00:02:00.400 | in anxiety, in depression,

00:02:02.720 | both positive and negative effects.

00:02:04.420 | We'll talk about sex differences

00:02:05.660 | in terms of women versus men

00:02:08.120 | and how they react differently to cannabis.

00:02:09.920 | And I would be entirely remiss

00:02:11.500 | if I didn't include a conversation about cannabis,

00:02:14.480 | meaning THC, CBD, hybrid strains, et cetera,

00:02:17.800 | in creativity and different modes of thinking.

00:02:20.440 | Because as many of you probably know

00:02:22.580 | or at least have heard about,

00:02:24.540 | cannabis can impact the way that we think,

00:02:27.240 | the types of memory systems we can access

00:02:29.440 | and what's called convergent and divergent thinking,

00:02:31.340 | which is one way of conceptualizing

00:02:33.680 | what is commonly referred to as creativity.

00:02:36.820 | So today's discussion is going to include

00:02:39.240 | a lot of information,

00:02:40.420 | but I promise to make it clear and accessible to all of you,

00:02:42.920 | regardless of whether or not

00:02:43.920 | you have a background in biology or not.

00:02:46.320 | And today's discussion will also be quite nuanced.

00:02:49.360 | You'll find me routinely reading

00:02:51.120 | directly from specific research papers,

00:02:53.300 | something that of course we always do on this podcast.

00:02:56.660 | But today I'm really going to dig into

00:02:58.200 | some of the finer points of the methodology in papers

00:03:01.420 | and some of the statistics that were used

00:03:03.800 | and the specific populations of people that were studied.

00:03:06.640 | Because as it turns out,

00:03:07.880 | there are instances that we will discuss

00:03:09.720 | in which the use of cannabis

00:03:11.440 | can be immensely beneficial to one group

00:03:14.160 | and yet can be entirely detrimental to another group,

00:03:17.480 | even at equivalent dosages

00:03:19.360 | and depending on a number of different factors.

00:03:21.560 | So we will discuss what those factors are.

00:03:23.760 | Just to give you a brief overview

00:03:25.520 | of the kind of structure I'm going to put on today's episode,

00:03:28.520 | we will review, of course, cannabis and its various forms.

00:03:31.400 | I'll talk about some of the biology,

00:03:32.520 | but we are going to really drill into how dosage,

00:03:36.120 | that is the concentration of THC relative to CBD,

00:03:39.880 | impacts whether or not cannabis

00:03:41.640 | is going to have one effect or another.

00:03:43.080 | We will also talk about the frequency of use,

00:03:46.280 | daily use, multiple times per day use,

00:03:49.040 | weekly use or monthly or occasional use.

00:03:51.480 | We will also talk about different professions

00:03:53.600 | and how some people may have a little bit more leeway

00:03:55.800 | in terms of whether or not they decide to use cannabis

00:03:58.560 | or any of its various component chemical constituents,

00:04:02.280 | that is CBD or THC, et cetera.

00:04:04.920 | And for other professions,

00:04:06.680 | it might be entirely inappropriate

00:04:08.280 | because of the particular kinds of cognitive tasks

00:04:10.600 | those professions demand.

00:04:12.080 | We will also talk about genetic predisposition,

00:04:14.680 | again, sex differences, hormone effects.

00:04:16.760 | And I will also touch on

00:04:17.860 | what I think is the most important variable

00:04:20.200 | in determining whether or not cannabis

00:04:22.580 | is right or wrong for you.

00:04:24.920 | And that is your age at which you are considering

00:04:28.160 | starting or continuing use or ceasing use.

00:04:31.200 | What I can assure you is that by the end of today's podcast,

00:04:34.080 | you will have a quite thorough understanding of cannabis,

00:04:37.360 | how it works, what it does,

00:04:39.080 | what its potential benefits can be,

00:04:40.920 | what its potential hazards are,

00:04:43.000 | and whether or not it's right for you

00:04:44.800 | and the people that you know.

00:04:45.960 | I'm excited to announce that the Huberman Lab Podcast

00:04:48.040 | has now launched a premium channel.

00:04:49.920 | The purpose of the premium channel is several fold.

00:04:51.780 | First of all, I will be hosting regular AMAs,

00:04:54.480 | Ask Me Anythings, where you can ask me anything,

00:04:56.760 | and I will provide answers in depth

00:04:58.680 | to your specific questions about science

00:05:00.440 | and science-related tools for mental health,

00:05:02.680 | physical health, and performance.

00:05:04.440 | Now, there is a nominal cost to the premium channel.

00:05:06.740 | It's $10 per month, or you can pay $100 for the entire year.

00:05:10.880 | I should mention, however,

00:05:12.160 | that a significant portion of the funds

00:05:13.800 | raised through the premium channel

00:05:15.480 | are going to support not just the Huberman Lab Podcast,

00:05:17.840 | which we will continue to release every Monday on schedule,

00:05:21.480 | of zero cost to all consumers,

00:05:23.460 | content on mental health, physical health, and performance,

00:05:27.360 | but proceeds from the premium channel

00:05:29.920 | will also be used to fund research,

00:05:31.840 | in particular, research done on human beings,

00:05:33.900 | so not animal models, but on human beings,

00:05:35.960 | which I think we all agree is a species

00:05:37.760 | that we are most interested in,

00:05:39.960 | and we are going to specifically fund research

00:05:42.960 | that is aimed toward developing further protocols

00:05:45.580 | for mental health, physical health, and performance,

00:05:47.620 | and those protocols will be distributed

00:05:49.520 | through all channels, not just the premium channel,

00:05:51.940 | but through all channels,

00:05:52.780 | Huberman Lab Podcast and other media channels.

00:05:54.940 | So the idea here is to give you information

00:05:57.520 | to your burning questions in depth

00:05:59.720 | and allow you the opportunity to support

00:06:01.900 | the kind of research that provides

00:06:03.560 | those kinds of answers in the first place.

00:06:05.640 | Now, an especially exciting feature of the premium channel

00:06:07.980 | is that the Tiny Foundation has generously offered

00:06:10.940 | to do a dollar-for-dollar match

00:06:12.560 | on all funds raised for research through the premium channel.

00:06:16.220 | So this is a terrific way that they're going to amplify

00:06:18.840 | whatever funds come in through the premium channel

00:06:20.800 | to further support research for science

00:06:22.840 | and science-related tools for mental health,

00:06:24.640 | physical health, and performance.

00:06:26.160 | If you'd like to sign up

00:06:27.000 | for the Huberman Lab premium channel,

00:06:28.760 | again, there's a cost of $10 per month,

00:06:30.820 | or you can pay $100 upfront for the entire year.

00:06:33.580 | That will give you access to all the AMAs.

00:06:35.920 | You can ask questions and get answers to your questions,

00:06:38.800 | and you'll, of course, get answers to all the questions

00:06:41.400 | that other people ask as well.

00:06:42.780 | There will also be some premium content,

00:06:44.720 | such as transcripts of the AMAs

00:06:46.540 | and various transcripts and protocols

00:06:48.440 | of Huberman Lab podcast episodes not found elsewhere.

00:06:51.680 | And again, you'll be supporting research

00:06:53.980 | for mental health, physical health, and performance.

00:06:56.340 | You can sign up for the premium channel

00:06:57.760 | by going to HubermanLab.com/premium.

00:07:00.420 | Again, that's HubermanLab.com/premium.

00:07:03.300 | Before diving into all of that,

00:07:04.540 | I'd like to highlight a new,

00:07:06.280 | what I think is very useful and zero-cost resource.

00:07:10.120 | This resource is what's called non-sleep deep rest,

00:07:13.580 | or NSDR protocol.

00:07:15.700 | I've talked many times before on the Huberman Lab podcast

00:07:17.960 | about non-sleep deep rest, AKA NSDR.

00:07:21.960 | NSDR is sort of an umbrella term

00:07:24.100 | for a variety of different practices.

00:07:26.660 | So these are behavioral practices

00:07:28.180 | that allow you to direct your brain and body

00:07:30.500 | into a particular state.

00:07:32.960 | And most typically, that state is one of deep relaxation,

00:07:36.160 | but also one in which you can access

00:07:39.100 | your bodily and brain systems for teaching yourself

00:07:42.840 | how to relax in real time

00:07:44.960 | and how to recover some of the sleep

00:07:47.620 | that you may not be getting at night,

00:07:49.600 | and to restore levels of dopamine

00:07:52.200 | in particular areas of the brain

00:07:53.700 | that are involved in motivation

00:07:55.060 | and cognitive and motor control.

00:07:56.960 | Basically, NSDR is a wonderfully restorative tool.

00:08:00.340 | This has been demonstrated many times over now

00:08:02.620 | through quality peer-reviewed science.

00:08:04.260 | And there are neurochemical benefits

00:08:05.960 | and there are physical benefits,

00:08:07.020 | and there are certainly psychological benefits.

00:08:09.540 | I highly recommend NSDR to anybody

00:08:12.420 | that has trouble falling asleep

00:08:14.660 | or that wakes up in the middle of the night

00:08:16.060 | and needs to get better at falling back asleep,

00:08:18.040 | as well as to anyone out there

00:08:19.560 | that has issues with anxiety

00:08:20.940 | or sort of self-regulation of any kind.

00:08:22.720 | And if you don't have any of those issues,

00:08:24.580 | it's also immensely beneficial just as a restorative

00:08:27.120 | for leaning back into focus work of any kind.

00:08:29.320 | Now, a number of people have reached out

00:08:30.680 | about finding NSDR protocols,

00:08:32.360 | and there are a number of different good ones out there

00:08:34.200 | floating around.

00:08:35.100 | I've decided to put a zero-cost NSDR script

00:08:39.060 | out there on the internet for people to access.

00:08:41.020 | So you can find it by going to YouTube

00:08:42.740 | and simply put my last name, Huberman and NSDR,

00:08:46.440 | into the search function.

00:08:48.060 | This is a YouTube channel that's hosted by Virtusan,

00:08:50.780 | which has a terrific app that includes NSDR

00:08:53.100 | and a number of other health and wellness protocols.

00:08:55.700 | But they've been quite generous

00:08:56.780 | in hosting a 10-minute NSDR read by me.

00:08:59.980 | This NSDR is distinct from,

00:09:01.960 | although I should say similar to Yoga Nidra,

00:09:04.260 | which some of you are familiar with.

00:09:06.380 | This NSDR is different than Yoga Nidra

00:09:09.100 | in the sense that it doesn't have intentions.

00:09:11.140 | There's no mystical component.

00:09:12.540 | And I describe a little bit of the science

00:09:14.760 | and why specific components of the NSDR included,

00:09:17.420 | things like long exhale breathing.

00:09:19.020 | I talk about perceptual shifts

00:09:20.460 | and how to move from thinking and planning

00:09:22.660 | to pure sensation.

00:09:23.740 | If none of that makes sense right now,

00:09:25.240 | it'll make total sense after listening to the NSDR script.

00:09:28.340 | Again, it's a 10-minute NSDR script read by me.

00:09:32.020 | You can do this first thing in the morning when you wake up,

00:09:34.300 | especially if you didn't get enough sleep that night

00:09:36.460 | and you're feeling a little bit fatigued

00:09:38.180 | and you need to lean into the day with full vigor.

00:09:40.220 | You could do it at any point during the day,

00:09:42.100 | or if you wake up in the middle of the night.

00:09:43.420 | Again, this is a zero-cost resource for you.

00:09:45.980 | You can find it by going to YouTube,

00:09:47.300 | put my last name in, and NSDR.

00:09:49.640 | I encourage you to try it.

00:09:51.020 | And if you like it, or frankly, if you don't,

00:09:54.200 | you can just put that in the comment section

00:09:55.800 | there on YouTube.

00:09:56.880 | And I've put it there as a free resource to you

00:09:59.580 | so that you can benefit from the research-backed,

00:10:03.120 | peer-reviewed studies that point to NSDR

00:10:05.180 | as a very useful practice.

00:10:07.460 | Before we begin, I'd like to emphasize that this podcast

00:10:09.900 | is separate from my teaching and research roles at Stanford.

00:10:12.660 | It is, however, part of my desire and effort

00:10:14.860 | to bring zero-cost-to-consumer information about science

00:10:17.460 | and science-related tools to the general public.

00:10:20.140 | In keeping with that theme,

00:10:21.220 | I'd like to thank the sponsors of today's podcast.

00:10:23.920 | Our first sponsor is Levels.

00:10:25.940 | Levels is a program that lets you see

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00:10:28.980 | by giving you real-time feedback on your diet

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00:10:34.940 | in your immediate and long-term health

00:10:36.780 | is how well you're managing your blood glucose

00:10:39.020 | or blood sugar.

00:10:40.060 | I started using Levels about a year ago

00:10:41.860 | as a way to see how different foods

00:10:43.380 | and different lifestyle factors

00:10:45.380 | were impacting my blood glucose levels.

00:10:47.740 | So for instance, it allowed me to see how different foods

00:10:50.020 | and particular macronutrients

00:10:51.460 | and combinations of macronutrients

00:10:53.420 | would either peak or trough my blood sugar

00:10:56.980 | or keep my blood sugar steady.

00:10:59.060 | It also allowed me to see how working out

00:11:01.420 | with weights or running, how that impacted my blood glucose.

00:11:04.340 | So for me, it was a fascinating experiment

00:11:06.380 | unto myself as to how my meal schedule,

00:11:10.680 | the specific foods I was eating,

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00:14:02.260 | On many episodes of the Huberman Lab Podcast,

00:14:04.300 | we talk about supplements.

00:14:05.820 | While supplements aren't necessary for everybody,

00:14:07.960 | many people derive tremendous benefit from them.

00:14:10.500 | Things like enhancing sleep and the depth of sleep,

00:14:13.140 | or for enhancing focus and cognitive ability,

00:14:15.860 | or for enhancing energy or adjusting hormone levels

00:14:19.140 | to optimal range for you.

00:14:20.700 | The Huberman Lab Podcast is now partnered

00:14:22.440 | with Momentus Supplements.

00:14:23.780 | We partnered with Momentus for a number of important reasons.

00:14:26.460 | First of all, the quality of their ingredients

00:14:28.900 | is exceptional, it's really second to none.

00:14:31.180 | Second of all, they ship internationally,

00:14:32.960 | and that was important to us

00:14:34.020 | because a number of you reside outside of the United States.

00:14:36.780 | Third, we've worked with Momentus very closely

00:14:39.300 | to develop single ingredient formulations.

00:14:41.720 | Now, this turns out to be very important

00:14:43.620 | because if you're going to take supplements,

00:14:45.820 | you want to know what's working for you and what isn't.

00:14:48.260 | And of course, you want to optimize the cost efficiency

00:14:51.420 | and the biological efficiency of those supplements.

00:14:54.460 | To find the supplements we discuss

00:14:55.780 | on the Huberman Lab Podcast,

00:14:57.020 | you can go to Live Momentus, spelled O-U-S,

00:14:59.660 | livemomentus.com/huberman.

00:15:02.220 | And I should just mention that the library

00:15:03.600 | of those supplements is constantly expanding.

00:15:05.780 | Again, that's livemomentus.com/huberman.

00:15:08.920 | Let's talk about cannabis.

00:15:10.700 | And when we refer to cannabis,

00:15:12.420 | we are indeed referring to marijuana or the marijuana plant.

00:15:16.560 | Now, cannabis plants come in different strains

00:15:19.220 | or different varieties, and those different strains

00:15:22.280 | are indeed different genetic strains.

00:15:25.180 | So just as animals and humans

00:15:26.940 | have different genetic backgrounds

00:15:28.540 | and they can be crossed to one another

00:15:30.140 | to yield further genetic variation in the offspring,

00:15:34.780 | plants can be hybridized to one another in various ways

00:15:38.620 | through grafting or through the use

00:15:40.260 | of different types of seed combinations, et cetera,

00:15:43.100 | in order to generate different strains.

00:15:45.240 | There are also naturally occurring differences

00:15:47.820 | in the strains of plants,

00:15:49.520 | and the cannabis plant is no exception.

00:15:52.500 | So for instance, in the context of a discussion

00:15:55.220 | about cannabis and its medicinal uses and recreational uses,

00:15:59.500 | we need to distinguish between the sativa variety,

00:16:03.940 | the indica variety, a variety called ruderalis,

00:16:08.380 | that's not often discussed,

00:16:10.120 | and hybrids of sativa, indica, and ruderalis.

00:16:13.940 | Before diving into the different strains of cannabis

00:16:16.020 | and how they impact the brain and body both similarly

00:16:18.740 | and differently, I want to emphasize

00:16:21.540 | that the cannabis plant contains a number

00:16:24.140 | of different psychoactive compounds.

00:16:26.220 | Now, the most powerful of those compounds is THC.

00:16:29.980 | The technical name for it is delta-9-tetrahydrocannabinol,

00:16:34.980 | but THC, as I'll refer to it,

00:16:37.940 | is just one of the psychoactive

00:16:40.180 | and biologically active compounds within cannabis plants.

00:16:44.240 | There's also CBD, which is technically referred

00:16:48.500 | to as cannabidiol, and cannabidiol, CBD,

00:16:53.480 | is known to be used for things like pain management,

00:16:56.620 | anxiety management, and other medicinal purposes.

00:16:59.580 | We will talk about the efficacy of CBD for those purposes,

00:17:03.060 | as well as some of, believe it or not,

00:17:04.820 | some of the dangers of CBD,

00:17:06.520 | depending on where it's sourced and the dosage, et cetera.

00:17:10.360 | So we've got THC, CBD, and also CBN, or cannabidiol.

00:17:15.360 | CBN is less often discussed.

00:17:18.380 | You're going to hear a lot less

00:17:19.620 | about CBN-containing products out there,

00:17:22.780 | CBN-containing medicines,

00:17:24.120 | but it is relevant to today's discussion,

00:17:25.840 | so it will come up a bit.

00:17:27.040 | Now, I will be sure to provide more specificity

00:17:29.380 | to what I'm about to say, but very broadly speaking,

00:17:33.440 | THC is largely responsible

00:17:35.620 | for the psychoactive effects of cannabis,

00:17:39.140 | that is, the changes in mood,

00:17:40.540 | the changes in bodily state and sensation, et cetera,

00:17:44.660 | whereas CBD, and to some extent CBN,

00:17:48.580 | have profound effects on the brain and body,

00:17:52.160 | but they don't tend to give people the sensation

00:17:54.380 | of altered perception, altered mood, et cetera.

00:17:58.080 | Some people might say they are not the component of cannabis

00:18:00.960 | that "gets you high,"

00:18:03.120 | although today we will really drill

00:18:04.360 | into what the high itself represents

00:18:06.660 | in terms of chemical systems in the brain and body,

00:18:09.360 | and what we will soon learn is that what we think of

00:18:13.380 | as being high actually includes a number

00:18:16.260 | of different changes in the brain and body,

00:18:17.820 | some of which can be best explained by CBD, not by THC,

00:18:22.460 | which runs counter to what most people out there

00:18:24.940 | know and believe.

00:18:26.380 | So broadly speaking, we have THC, CBD, and CBN,

00:18:30.880 | but I want to point out that the cannabis plant

00:18:33.140 | has over 70, seven zero, 70 different psychoactive compounds,

00:18:37.260 | many of which still have not been studied

00:18:40.100 | in isolation and in detail.

00:18:42.140 | So there's a big future of research for cannabis

00:18:44.740 | and for THC and THC-related psychoactive compounds,

00:18:48.340 | as well as for CBD and CBN.

00:18:50.760 | Today we're mainly going to focus on THC and CBD,

00:18:54.300 | as I mentioned before.

00:18:55.620 | I should also point out that the cannabis plant

00:18:57.300 | has over 400 biologically active compounds.

00:19:01.180 | So these are biologically active compounds

00:19:03.180 | that may or may not have psychoactive properties,

00:19:06.660 | that may or may not be useful for pain relief, et cetera.

00:19:09.460 | Again, there is a vast landscape for exploration

00:19:12.780 | of the cannabis plant and of hemp for what they include

00:19:16.700 | that could be beneficial to us or detrimental to us.

00:19:20.000 | So again, a lot more work to do.

00:19:21.820 | Today, we're going to really try and stay on target

00:19:23.880 | with what we already know

00:19:25.740 | and where there are certain exciting mysteries

00:19:28.380 | or intriguing mysteries about what we ought to explore

00:19:30.980 | more, I will certainly highlight those.

00:19:33.100 | Let's go back to the different strains of the cannabis plant,

00:19:36.980 | sativa, indica, and ruderalis,

00:19:39.220 | and explore how each of those differentially impacts

00:19:43.360 | the brain and body, because therein I think we can start

00:19:45.860 | to learn a lot about this incredible plant

00:19:48.540 | that is the cannabis plant.

00:19:50.280 | And whether or not you are a user of cannabis

00:19:53.120 | or whether or not you are entirely opposed to cannabis use,

00:19:56.460 | understanding how cannabis works in the brain and body

00:19:59.540 | itself is absolutely fascinating and can teach you a lot

00:20:03.060 | about how your brain and body work at a basic level.

00:20:06.300 | And can tell you a lot about how your brain and body

00:20:08.580 | will react to different life events

00:20:10.240 | and how your mood is established and stabilized

00:20:13.220 | and how your appetite is established and stabilized

00:20:16.220 | and so on.

00:20:17.180 | So we have the three major strains of cannabis,

00:20:19.100 | sativa, indica, and ruderalis.

00:20:21.900 | And for sake of today's conversation,

00:20:23.680 | we can pretty much cross off ruderalis.

00:20:26.000 | It's not often consumed and components of ruderalis

00:20:30.120 | are not often consumed for medicinal

00:20:32.920 | or recreational purposes.

00:20:34.360 | Let's focus on sativa and indica.

00:20:37.560 | People will consume the sativa variety of cannabis,

00:20:42.900 | either by edible or by smoking cannabis,

00:20:47.280 | or they will consume the indica variety of cannabis,

00:20:50.000 | again, by edible or by smoking cannabis,

00:20:53.360 | or sometimes they will take it in a transdermal form

00:20:56.340 | or a sublingual form.

00:20:58.360 | There are a bunch of different ways to get the cannabis

00:21:01.260 | into the body, but there's a clear distinction

00:21:04.420 | between sativa and indica that actually shows up first

00:21:07.660 | in the structure of the plant.

00:21:09.780 | At their extremes, meaning in a pure strain of sativa,

00:21:14.140 | it tends to be a taller plant, a longer stalk,

00:21:16.660 | believe it or not.

00:21:17.640 | And actually the length of the leaves

00:21:19.440 | is quite a bit longer.

00:21:20.780 | Whereas the indica plant tends to be more short and stout.

00:21:25.020 | And for those aficionados out there,

00:21:27.860 | I'm sure you know a lot of the other specific features

00:21:29.860 | of sativa versus indica.

00:21:31.280 | But already what we're talking about is the same plant,

00:21:34.340 | cannabis, with two very different morphologies or shapes.

00:21:38.280 | You might say, well, why is this interesting

00:21:39.620 | or important to how it affects me or affects other people

00:21:43.020 | for medicinal recreational purposes?

00:21:44.800 | Well, it turns out that even though they are the same plant,

00:21:47.720 | these two different genetic varieties,

00:21:49.660 | because of the way that they grow

00:21:52.700 | and the way they capture sunlight and the way,

00:21:55.300 | believe it or not, that the different plants

00:21:57.520 | within that strain interact with one another,

00:21:59.780 | 'cause believe it or not,

00:22:00.920 | plants are interacting with one another,

00:22:02.940 | they actually bring different elements

00:22:04.900 | of the psychoactive compounds to different components

00:22:07.300 | within the leaves and the so-called buds.

00:22:09.340 | The takeaway is that when consumed,

00:22:12.580 | and when I say consumed, I want to be very clear,

00:22:14.460 | I don't necessarily just mean oral consumption

00:22:17.880 | or eating cannabis sativa by edible.

00:22:22.060 | I also mean smoking it, and that could be, you know,

00:22:25.040 | people will, just like with tobacco,

00:22:27.740 | the way that they bring the psychoactive components

00:22:30.240 | into their bloodstream and into their brain and body

00:22:32.700 | is to essentially heat the dried leaves

00:22:36.260 | of the cannabis plant.

00:22:38.580 | Then the heat liberates some of the psychoactive components

00:22:42.720 | that when inhaled into the lungs,

00:22:44.560 | because the lungs include a lot of vasculature,

00:22:46.820 | a lot of basically blood vessels and capillaries,

00:22:50.400 | that the psychoactive components

00:22:53.700 | are actually directly absorbed from the lungs

00:22:55.580 | into the bloodstream,

00:22:56.440 | and they can cross into the bloodstream

00:22:58.040 | and permeate throughout the body

00:23:00.260 | and cross the so-called blood-brain barrier.

00:23:02.240 | So in other words, burning the plant liberates the smoke

00:23:06.800 | that contains the psychoactive compounds,

00:23:09.640 | and those are inhaled into the lungs

00:23:11.520 | and then get into the brain and body

00:23:13.140 | and act on the brain and body.

00:23:14.620 | And the major effect of sativa varieties

00:23:17.220 | are to create a high, if you will,

00:23:19.940 | and I'm putting this in air quotes

00:23:20.980 | for those of you that are listening,

00:23:22.440 | but to also act as a stimulant.

00:23:24.460 | The sativa varieties tend to make people

00:23:26.260 | feel kind of invigorated, somewhat alert.

00:23:29.040 | It doesn't tend to be as much of a sedative

00:23:31.040 | as some of the other varieties.

00:23:32.720 | Some people report heightened sense of focus

00:23:35.140 | or heightened sense of creativity.

00:23:36.680 | We will talk a little bit later on

00:23:37.880 | as to whether or not they actually are achieving

00:23:39.820 | heightened levels of focus and creativity,

00:23:41.780 | or whether or not they just perceive themselves

00:23:43.460 | to have heightened levels of focus and creativity.

00:23:45.480 | The sativa varieties tend to make people

00:23:47.880 | feel a little bit less susceptible

00:23:50.520 | to pain and noxious stimuli,

00:23:52.780 | which are basically stimuli that you don't like.

00:23:55.900 | So the sativa varieties are often prescribed

00:23:59.260 | or are used in the recreational context

00:24:02.840 | for pain management and relief.

00:24:05.200 | Basically, the sativa variety is known to include

00:24:08.100 | a sort of head-biased effect.

00:24:10.460 | So here we're talking about subjective effects,

00:24:12.920 | and of course, these will vary

00:24:14.200 | from one individual to the next.

00:24:15.980 | Some people will smoke cannabis sativa

00:24:18.020 | or ingest cannabis sativa orally

00:24:20.280 | and will feel an entirely different array of effects,

00:24:24.400 | but most people, the majority of people,

00:24:26.440 | experience a sort of head-centered high alertness focus

00:24:30.640 | and a sense that they're more creative.

00:24:33.040 | Contrast that with the indica varieties of cannabis,

00:24:36.320 | and when people smoke or eat or ingest indica varieties,

00:24:40.960 | the psychoactive components of indica,

00:24:43.100 | and again, this is pure indica,

00:24:44.620 | so not hybridized with sativa at all,

00:24:46.480 | but just pure indica,

00:24:47.800 | tend to lead to more full-bodied effects.

00:24:51.040 | People report feeling more complete full-body relaxation,

00:24:55.340 | more of a sedative effect.

00:24:57.560 | Indica cannabis is often prescribed

00:25:00.440 | and/or used recreationally

00:25:02.120 | in order to achieve a state of sleep

00:25:04.840 | or to help relieve anxiety,

00:25:06.780 | so less of a stimulant effect,

00:25:09.280 | and we will talk about why,

00:25:10.960 | literally the underlying neural circuits,

00:25:12.960 | that lead to the sativa variety

00:25:15.760 | causing more of a elevated mood and a head high, if you will,

00:25:19.880 | and the indica varieties being more full-body relaxation.

00:25:23.000 | One of the ways to remember the distinction

00:25:24.420 | between the effects of cannabis sativa and cannabis indica

00:25:27.560 | was relayed to me by a friend

00:25:29.160 | who actually was a chronic, meaning every day, all day,

00:25:32.540 | consumer of marijuana.

00:25:34.800 | He basically smoked marijuana for 20 years

00:25:36.680 | before quitting about four or five years ago,

00:25:39.020 | and he said that indica is often referred to as indicouch,

00:25:43.360 | meaning laid back in the couch,

00:25:45.860 | and that can help you remember

00:25:47.580 | that the indica varieties of cannabis

00:25:50.020 | do tend to be more sedative in their effects.

00:25:52.860 | Okay, so there's sativa and there's indica,

00:25:54.520 | and then now there are hybrid strains.

00:25:56.780 | So marijuana growers and people who specialize

00:26:00.200 | in creating novel varieties of the cannabis plant,

00:26:03.020 | again, I'm using the words cannabis and marijuana

00:26:05.780 | more or less interchangeably here,

00:26:08.000 | they are very good at creating new strains of plant

00:26:12.200 | that might be 25% sativa and 75% indica or vice versa,

00:26:17.200 | or 50/50 or 90/10.

00:26:20.080 | Essentially what's happening nowadays

00:26:21.620 | is that through plant biology, plant genetics, I should say,

00:26:26.320 | growers are getting quite efficient

00:26:28.960 | at creating a variety of different strains

00:26:31.560 | of the marijuana plant that give rise to very nuanced

00:26:35.840 | and distinct effects on brain and body.

00:26:39.040 | In fact, so much so that there's now a new nomenclature,

00:26:42.680 | a new language emerging around cannabis

00:26:46.540 | and the development of novel strains of cannabis

00:26:48.780 | for medicinal and or recreational purposes.

00:26:51.780 | And while this might sound a little bit medical

00:26:54.960 | or a little bit clinical to some people,

00:26:57.440 | believe it or not, this is the nomenclature

00:26:59.140 | that it's now typically used.

00:27:00.500 | People still refer to the sativa, indica, and hybrid strains,

00:27:04.760 | but there's now also a description

00:27:06.480 | of so-called type one, type two, and type three strains

00:27:11.240 | for any given sativa, indica, or hybrid strain.

00:27:14.800 | Okay, so just to put this clearly in your mind,

00:27:17.200 | you've got sativa varieties, that is pure sativa varieties.

00:27:20.440 | You have indica varieties, again, pure indica,

00:27:24.400 | and then you have hybrid varieties.

00:27:27.040 | And beneath each of those, you have type one, type two,

00:27:30.280 | and type three strains of indica, sativa,

00:27:35.280 | or hybrid varieties.

00:27:38.140 | What are type one, type two, and type three?

00:27:41.340 | Well, type one, type two, and type three strains

00:27:45.420 | are strains that have varying amounts

00:27:47.760 | or ratios of THC to CBD.

00:27:51.320 | So for instance, type one strain.

00:27:54.760 | So for instance, you could have a pure sativa type one

00:27:58.160 | or a type one pure sativa or a type one indica.

00:28:01.200 | Those are going to have the greatest amount

00:28:04.240 | of THC relative to CBD.

00:28:06.540 | And I really want to emphasize this,

00:28:08.240 | understanding the ratio of THC to CBD

00:28:11.520 | can help explain a lot or even predict a lot

00:28:14.380 | about how a given strain of cannabis will impact somebody.

00:28:18.740 | For instance, because THC is largely responsible

00:28:22.880 | for the typical psychoactive components of cannabis,

00:28:28.120 | so what I mean here is if somebody is ingesting sativa

00:28:31.320 | and it routinely makes them feel more energized,

00:28:34.640 | elevates their mood,

00:28:35.820 | gives them a heightened sense of creativity,

00:28:38.280 | if that's what they experience,

00:28:40.200 | and they're taking a type one version of that,

00:28:42.680 | that means that it's quite rich in THC and very little CBD.

00:28:47.500 | However, if they were to take a type one version of sativa

00:28:51.280 | and it feels far too strong, like too much energy,

00:28:53.560 | or they felt like they were too much in their head,

00:28:55.480 | nowadays, there are strains of sativa

00:28:59.080 | that have been genetically engineered.

00:29:01.520 | And I don't mean by an engineer tinkering away

00:29:03.680 | with gene engineering in a kind of crisper creating mutants,

00:29:08.600 | but literally by hybridizing,

00:29:10.020 | crossing different plants to one another, okay?

00:29:13.140 | Creating in a natural context,

00:29:15.120 | the same way plants in the outside world

00:29:17.320 | would sometimes hybridize to one another.

00:29:19.620 | Creating a variety that's perhaps type two,

00:29:23.580 | which is going to have less THC and more CBD,

00:29:28.580 | or a type three,

00:29:29.480 | which is going to be very high CBD and very little THC.

00:29:33.400 | And the same is also true for the indica varieties.

00:29:36.480 | So I want to make sure that everyone understands this

00:29:38.200 | because it becomes very important

00:29:39.200 | for understanding the biology of cannabis

00:29:41.520 | and predicting positive versus negative effects of cannabis.

00:29:46.520 | Sativa has this kind of stimulant-like effect

00:29:49.420 | and tends to be more of a head high, if you will.

00:29:51.600 | Indica tends to be more full-bodied than lead

00:29:53.600 | to more in the couch, as I referred to it before,

00:29:56.040 | pun intended.

00:29:58.240 | Deep relaxation, reduced insomnia, et cetera.

00:30:02.020 | Now within each of those, sativa and indica,

00:30:03.680 | you have type one, type two, and type three.

00:30:05.220 | And that has everything to do with how much THC,

00:30:09.220 | which is the dominant psychoactive compound versus CBD,

00:30:13.660 | which has other effects mainly on the body,

00:30:15.960 | but not so much on the brain

00:30:18.300 | and modes of thinking and mood, et cetera.

00:30:20.080 | How much THC versus CBD is present.

00:30:22.200 | And again, type one is THC dominant,

00:30:25.080 | type two kind of equal ratios, if you will,

00:30:27.380 | of THC and CBD, and type three tend to be high CBD.

00:30:30.800 | Okay, so already we've got some categorization here

00:30:32.720 | that hopefully isn't overwhelming to you,

00:30:34.640 | but this turns out to be extremely important

00:30:37.100 | if you want to understand how cannabis works

00:30:39.440 | and predict the effects of cannabis.

00:30:41.360 | I'd like to take a quick break

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00:31:55.760 | Okay, so somewhat surprisingly,

00:31:57.280 | we're going to set aside cannabis.

00:31:58.680 | We're going to take what we know about sativa, indica,

00:32:01.200 | type 1, type 2, type 3, CBD, et cetera.

00:32:03.600 | We're just going to set that aside for a moment.

00:32:05.640 | Why would we do that?

00:32:06.480 | Well, we have to ask ourselves,

00:32:08.600 | why would any of these plants,

00:32:10.480 | why would any of these compounds, THC, CBD, sativa,

00:32:14.280 | indica, et cetera,

00:32:15.620 | why would any of that have any effect on us at all?

00:32:18.640 | And this discussion that we're about to have

00:32:21.720 | very much resembles the discussion

00:32:23.800 | that we had on a previous episode about nicotine.

00:32:26.480 | Because as many of you know,

00:32:28.000 | nicotine is a commonly used substance.

00:32:30.420 | In fact, if we were to look at

00:32:31.500 | the three most commonly used drugs,

00:32:34.060 | alcohol will be the top of the list.

00:32:35.600 | Many billions of people regularly use alcohol

00:32:38.520 | or occasionally use alcohol.

00:32:40.740 | Many billions of people also use nicotine.

00:32:44.200 | It's the second most consumed drug.

00:32:46.720 | So more than 1 billion

00:32:48.480 | and probably closer to 2 billion people consume nicotine.

00:32:51.080 | And then the third most consumed drug is cannabis

00:32:55.480 | in one form or another.

00:32:57.160 | And many of you are probably shouting,

00:32:58.280 | what about caffeine?

00:32:59.120 | What about caffeine?

00:32:59.940 | Well, in the context of drugs

00:33:02.160 | and in particular addictive drugs,

00:33:03.580 | caffeine doesn't quite rise to the list.

00:33:06.160 | But if we were to look at caffeine

00:33:09.140 | and include in that list,

00:33:10.800 | caffeine would be above all of those, okay?

00:33:12.560 | But the most commonly used drugs are alcohol.

00:33:14.400 | Second after that is nicotine and then cannabis.

00:33:19.400 | Nicotine, as some of you may know,

00:33:21.860 | if you listen to the episode on nicotine,

00:33:23.320 | but even if you didn't,

00:33:25.280 | nicotine comes from the tobacco plant.

00:33:27.660 | And there are a few other plants that include nicotine.

00:33:29.600 | And typically it's brought into the brain and body

00:33:32.400 | by smoking tobacco, dipping tobacco,

00:33:34.240 | snuffing tobacco or vaping nicotine.

00:33:37.400 | Nicotine exists in the outside world in these plants,

00:33:41.640 | the tobacco plants.

00:33:42.800 | But the reason it has an effect on the body

00:33:44.640 | is that there are so-called

00:33:45.560 | nicotinic receptors in the body.

00:33:47.640 | Now those nicotinic receptors

00:33:48.880 | were named after nicotine, the compound,

00:33:51.260 | but they existed in the brain and body,

00:33:53.420 | not because of the existence of a tobacco plant,

00:33:55.980 | but because there are other chemicals in the body

00:33:59.080 | that naturally occur, namely acetylcholine

00:34:01.960 | that bind the nicotine receptor.

00:34:04.080 | Those chemicals such as acetylcholine

00:34:07.320 | that bind the nicotinic receptor in your brain and body

00:34:10.080 | create an enhanced sense of focus, et cetera, et cetera.

00:34:13.220 | But nicotine from tobacco binds that same receptor,

00:34:18.220 | but with much greater affinity

00:34:20.680 | and therefore also creates a state of focus,

00:34:23.560 | but a much greater one than we can achieve without nicotine.

00:34:27.080 | Okay, so you can see the nicotine episode

00:34:28.480 | if you want to learn more about that.

00:34:30.280 | In a very similar way,

00:34:33.060 | all of our brains and bodies

00:34:35.540 | from the time that we are conceived,

00:34:38.120 | believe it or not, very shortly after conception,

00:34:40.360 | if we want to be accurate,

00:34:41.740 | very early conception when you were in the womb,

00:34:44.360 | and still now, if you're listening to this,

00:34:47.040 | you have what are called cannabinoid receptors

00:34:51.800 | because you also have endogenous cannabinoids.

00:34:55.880 | What do we mean by that?

00:34:56.720 | You have receptors which are like little parking spots

00:34:59.460 | that are present on cells in your brain and body.

00:35:03.340 | And what we call a ligand,

00:35:05.680 | which is basically just a chemical that's released,

00:35:07.560 | parks in that receptor

00:35:09.720 | and causes a number of different biological effects.

00:35:12.720 | Cannabis contains compounds

00:35:17.340 | that also bind to those receptors.

00:35:19.480 | But here, I want to make a really clear distinction.

00:35:21.440 | We have what are called endogenous ligands.

00:35:23.660 | Those that just mean chemicals from within us

00:35:26.240 | that we make naturally,

00:35:27.360 | even if we never go near the cannabis plant

00:35:29.360 | or any other source of cannabis,

00:35:31.160 | we have chemicals that are created in us

00:35:34.200 | that park in those receptors and cause biological effects

00:35:38.320 | on mood, on perception, on the immune system,

00:35:40.320 | on hunger, et cetera.

00:35:41.620 | Again, without ever going anywhere near cannabis,

00:35:44.400 | we have these endogenous cannabinoids.

00:35:47.280 | Indogenous cannabinoids are floating around in us,

00:35:49.680 | or I should say they are released in us in particular ways,

00:35:52.080 | bind to these receptors

00:35:53.040 | and cause changes in mood, appetite, et cetera.

00:35:55.760 | They have many different effects on the brain and body.

00:35:57.720 | We will talk about those.

00:35:59.680 | But just like with nicotine,

00:36:01.200 | there are substances in the outside world,

00:36:03.280 | in this case, cannabis contains these substances,

00:36:06.800 | so things like THC and like CBD,

00:36:11.280 | that when ingested by smoking or vaping

00:36:14.040 | or by ingesting edibles,

00:36:15.640 | also will park in those same receptors,

00:36:20.160 | the cannabinoid receptors, and lead to biological effects.

00:36:24.360 | Now, it's a little bit misleading

00:36:25.560 | because we call them cannabinoid receptors

00:36:27.480 | as if they were there to bind cannabis,

00:36:31.440 | or just like we call the nicotine receptors

00:36:33.440 | and nicotinic receptors,

00:36:35.240 | it makes it seem as if they were there

00:36:36.880 | in order to bind nicotine from tobacco.

00:36:40.320 | But that's not the way our brains and bodies evolved.

00:36:42.560 | Our brains and bodies evolved for these receptors

00:36:45.600 | to make use of chemicals that exist within us

00:36:48.560 | called, again, endogenous chemicals.

00:36:51.480 | And those endogenous chemicals lead to certain effects,

00:36:54.200 | as I mentioned before.

00:36:55.440 | The key thing here,

00:36:56.580 | if you haven't understood anything I've said up until now,

00:36:59.360 | please understand this.

00:37:00.360 | The key thing is that THC and CBD

00:37:04.560 | and the other components of cannabis bind to those receptors,

00:37:08.420 | those endogenous cannabinoid receptors,

00:37:10.660 | the ones that we naturally make,

00:37:12.520 | with much greater affinity

00:37:14.800 | and exert a vastly greater potency

00:37:17.720 | and effect on mood and perception, et cetera,

00:37:20.820 | than do our endogenous cannabinoids.

00:37:23.940 | Another analogy that one could take

00:37:26.760 | in order to understand this

00:37:28.280 | would be hormones like testosterone and estrogen.

00:37:31.800 | Many people, I would say all people,

00:37:35.040 | make testosterone and estrogen to varying degrees.

00:37:37.600 | It's going to depend on whether or not you're male, female,

00:37:39.280 | your age, whether or not you've gone through puberty,

00:37:40.800 | et cetera, et cetera.

00:37:42.200 | But let's just say testosterone, for example.

00:37:45.360 | There's testosterone circulating in your body.

00:37:48.960 | That's true if you're male or female.

00:37:50.800 | And there are receptors called androgen receptors.

00:37:53.060 | We could even call them testosterone receptors.

00:37:56.080 | And the testosterone binds to those receptors

00:37:58.180 | and has effects on cells.

00:37:59.340 | It causes hair growth, changes the voice.

00:38:01.660 | It can affect libido.

00:38:02.920 | It affects all sorts of things in the brain and body,

00:38:04.640 | depending on which organ and tissue you're talking about.

00:38:07.740 | But of course, there are people

00:38:09.280 | that take synthetic testosterone

00:38:11.080 | or derivatives of testosterone.

00:38:14.000 | And some of those derivatives, for instance,

00:38:15.600 | in the bodybuilding community and the sports community,

00:38:17.600 | they will take things like Diana ball.

00:38:19.260 | These are modified versions of testosterone

00:38:23.160 | that can bind to the testosterone receptor

00:38:26.120 | with much greater affinity,

00:38:28.100 | or I should say the androgen receptor

00:38:29.820 | with much greater affinity

00:38:31.020 | and have supra physiological effects,

00:38:34.060 | effects that would essentially never be seen

00:38:36.880 | from testosterone that was endogenously,

00:38:41.760 | excuse me, endogenously released within the body.

00:38:45.600 | We could say the same thing for estrogen.

00:38:47.280 | There are estrogen receptors, they bind estrogen, okay?

00:38:51.820 | But if someone were to take synthetic estrogen

00:38:54.240 | or to ingest a plant compound that contains

00:38:56.720 | various estrogenic compounds,

00:38:58.080 | and those plants certainly exist out there,

00:39:00.680 | they can have supra physiological effects

00:39:03.240 | on those receptors.

00:39:04.800 | Why am I telling you this?

00:39:06.080 | Well, many people believe that because cannabis,

00:39:10.040 | marijuana is a plant and plants grow out of the ground

00:39:14.080 | and they're naturally occurring,

00:39:16.040 | and because we have receptors in our body

00:39:19.340 | that are there without the need to engineer them

00:39:23.040 | from some external source, right?

00:39:25.120 | They're in our genome, they program for it,

00:39:26.720 | and we're born with these things

00:39:27.700 | and we keep these our entire life.

00:39:30.080 | Many people mistakenly think,

00:39:31.800 | ah, you know, these plant compounds are safer for us

00:39:35.920 | or better for us or are somehow appropriate

00:39:38.060 | for us to ingest, but that's simply not true.

00:39:41.440 | And here, I'm not saying that cannabis

00:39:43.180 | is always a bad idea for people.

00:39:44.720 | There are certain populations and certain people

00:39:46.440 | for which it can be relatively safe recreationally,

00:39:49.520 | that's the truth, and there are other populations

00:39:51.440 | for which it can be downright dangerous

00:39:53.440 | recreationally or medicinally.

00:39:55.080 | And of course, there are medicinal purposes

00:39:57.400 | that are being explored and we'll talk more about that.

00:39:59.600 | But this is vital to understand

00:40:01.120 | because I think that when we hear,

00:40:02.580 | oh, it's from a plant, it's natural,

00:40:04.680 | and then you also have a receptor for these,

00:40:06.200 | endogenous cannabinoid receptors,

00:40:08.080 | and therefore the marriage of those two, right?

00:40:11.480 | The coming together of the chemical THC or CBD or both

00:40:15.360 | with these receptors is somehow supposed to happen

00:40:18.240 | as if this was a purpose of having these receptors,

00:40:21.440 | but it's simply not the case in the same way

00:40:23.200 | that the nicotinic receptors are not there

00:40:25.660 | because nicotine is good for us.

00:40:27.340 | They're there because there are compounds

00:40:28.640 | that exist within us that are good

00:40:30.940 | to bind to those receptors from time to time.

00:40:34.160 | Now, here's the key thing about,

00:40:36.240 | I guess today I'm saying there are a lot of key things,

00:40:37.760 | but here's another key thing about understanding cannabis

00:40:41.020 | in the way that it works, which is that THC and CBD,

00:40:45.760 | when they're brought into the brain and body

00:40:47.600 | by smoking or edible, et cetera,

00:40:50.440 | they bind to those receptors,

00:40:53.960 | those endogenous cannabinoid receptors,

00:40:56.080 | and they tap into the same systems

00:40:58.460 | that your endogenous cannabinoids would tap into,

00:41:01.800 | the ones that affect mood and energy and creativity

00:41:04.180 | and relaxation, et cetera,

00:41:05.880 | but they do so with thousand-fold greater potency.

00:41:10.880 | And as a consequence of that,

00:41:13.240 | your endogenous cannabinoids are out-competed.

00:41:16.820 | They really get no opportunity

00:41:18.620 | to interact with those receptors.

00:41:20.800 | And understanding that can lead

00:41:23.040 | to a very clear understanding of why, for instance,

00:41:25.580 | when people use cannabis to relieve anxiety

00:41:28.760 | or they use cannabis to enter a certain brain state

00:41:31.120 | for creativity or to enter sleep,

00:41:33.640 | why a dependence on cannabis starts to emerge.

00:41:37.080 | Because if they don't ingest cannabis,

00:41:39.540 | and again, ingest could mean smoke to bring THC in or CBD in

00:41:44.360 | or ingest orally or even transdermal or tincture

00:41:46.680 | or one of the other varieties,

00:41:48.380 | if they don't do that,

00:41:50.080 | then what happens is not only are the receptors

00:41:53.300 | not stimulated to the same degree

00:41:55.480 | or with the same potency that they normally are,

00:41:59.060 | but the endogenous cannabinoids

00:42:01.160 | can no longer have their effect.

00:42:02.620 | So people experience heightened levels of anxiety,

00:42:05.160 | disrupted mood, disrupted brain state, and so on.

00:42:09.880 | Now, again, I want to be very clear

00:42:11.900 | that I'm not trying to paint a picture of cannabis

00:42:13.980 | as all bad or even partially bad.

00:42:16.120 | What I want to do today is give you as much information I can

00:42:19.400 | as to how cannabis works,

00:42:21.440 | how its different component parts work,

00:42:23.000 | how the different types of cannabis work,

00:42:25.080 | and point to some of the valid medicinal uses

00:42:28.680 | and some of the recreational uses,

00:42:30.200 | and then lay out the landscape for you

00:42:33.040 | as to who is really most at risk

00:42:35.320 | in terms of psychoactive components, immune components,

00:42:39.640 | and so on and so forth

00:42:40.640 | so that you can make the most informed choice for you.

00:42:42.520 | I am not here to tell you what to do or what not to do.

00:42:45.960 | As I like to say, do as you wish, right?

00:42:49.700 | I mean, don't do as you wish

00:42:51.240 | if it harms other people or yourself,

00:42:52.440 | but do as you wish, but know what you're doing.

00:42:55.020 | So that's really my goal here.

00:42:56.520 | So as we begin to dive further into the biology,

00:42:58.600 | I think you'll start to get a clearer picture

00:43:00.520 | of why cannabis is so effective in some contexts,

00:43:03.740 | but also why it can create such massive suffering

00:43:07.720 | in other contexts because of the way that it out-competes

00:43:11.280 | your own natural endogenous cannabinoid systems.

00:43:14.560 | So let's talk about those endogenous cannabinoid systems,

00:43:16.760 | what they are and how they work,

00:43:18.660 | because that will give us a lens

00:43:20.400 | into what the higher potency or maximum impact

00:43:24.640 | of the various cannabis plant varieties and strains

00:43:27.120 | and THC and CBD and so forth, how and why those work.

00:43:30.960 | So what are the endogenous cannabinoids,

00:43:33.000 | these chemical substances that everybody makes?

00:43:36.860 | You make them, I make them,

00:43:38.380 | you've been making them basically

00:43:40.000 | from the time that you were conceived

00:43:41.200 | and you are going to make them until the time that you die.

00:43:43.880 | Whether or not they have the impact

00:43:45.520 | and the biological functions that I'm about to describe

00:43:47.640 | will depend a lot on whether or not

00:43:49.560 | you are using your own endogenous cannabinoids

00:43:53.240 | to park in those receptors

00:43:54.600 | that you also have from birth until death,

00:43:57.960 | or whether or not you are tickling those receptors

00:44:01.760 | or strongly activating those receptors

00:44:04.380 | using some external source like cannabis, THC, et cetera.

00:44:11.380 | The two main endogenous cannabinoids

00:44:14.000 | that we want to consider are anandamide,

00:44:16.680 | which we will refer to as EAE, so anandamide,

00:44:20.320 | and another one, which is arachidinoyl glycerol,

00:44:24.640 | arachidinoyl glycerol, which we will abbreviate 2AG.

00:44:28.140 | So let's just take EAE and 2AG,

00:44:31.620 | lump them together and talk about the endogenous cannabinoids

00:44:34.780 | just to make it simple.

00:44:35.880 | But if you want to do the deep dive

00:44:37.440 | on anandamide versus 2AG, please be my guest.

00:44:41.620 | The endogenous cannabinoids are released from neurons.

00:44:45.980 | What are neurons?

00:44:46.820 | Neurons are nerve cells,

00:44:48.580 | and nerve cells should be conceptualized like this.

00:44:52.360 | You have presynaptic neurons and postsynaptic neurons.

00:44:54.940 | Presynaptic neurons basically contain little vesicles,

00:44:57.740 | little bubbles full of neurotransmitter, which are chemicals.

00:45:02.020 | And when neurons are stimulated electrically,

00:45:05.140 | and that could be from a thought,

00:45:06.540 | it could be from the desire to move,

00:45:08.800 | it could be because of a drug,

00:45:10.700 | it could be because you're hungry,

00:45:12.500 | the relevant neurons will vomit out

00:45:16.340 | or will fuse, as we say, those little packets,

00:45:19.620 | those little bubbles of neurotransmitter

00:45:21.500 | into the gap between the pre- and postsynaptic neuron.

00:45:23.940 | We call that a synaptic cleft or the synapse.

00:45:26.540 | It's a little gap, a little space.

00:45:27.920 | And the neurotransmitter flows across that synapse,

00:45:30.760 | and some of it will park in little parking spots

00:45:33.480 | that we call receptors on the postsynaptic neuron side.

00:45:36.460 | Depending on which neurotransmitter it is,

00:45:38.400 | and a bunch of other things not worth going into right now,

00:45:41.340 | the parking of that chemical

00:45:43.400 | in those neurotransmitter receptors

00:45:44.800 | will either cause that neuron on the postsynaptic side

00:45:48.900 | to itself release neurotransmitter elsewhere,

00:45:52.700 | or it will quiet it down,

00:45:54.640 | so-called excitation and inhibition.

00:45:56.400 | That's kind of neurotransmission in a nutshell.

00:45:58.540 | If you don't understand it, no big deal.

00:46:00.220 | It's not going to prevent you

00:46:01.100 | from understanding today's discussion.

00:46:02.380 | If you understand even a small fraction

00:46:04.380 | of what I've just said,

00:46:05.780 | then it's going to allow you to understand

00:46:08.680 | not just today's discussion, but a lot of neuroscience

00:46:10.940 | with a lot more nuance and depth of understanding.

00:46:13.540 | The key thing to know about the endogenous cannabinoids

00:46:18.940 | is that unlike most neurotransmitters,

00:46:22.500 | they are released from the postsynaptic side.

00:46:25.700 | So what happens is neurotransmitter

00:46:27.920 | goes from presynaptic neuron to postsynaptic neuron,

00:46:31.100 | but under certain conditions,

00:46:33.000 | the postsynaptic neuron itself releases a chemical,

00:46:36.480 | and that chemical goes backward,

00:46:38.340 | what we call retrogradely, to the presynaptic neuron,

00:46:41.340 | binds the receptors there,

00:46:42.980 | and changes the probability that the presynaptic neuron

00:46:46.580 | will release neurotransmitter.

00:46:48.080 | Put simply, endogenous cannabinoids

00:46:52.460 | tend to decrease the probability

00:46:55.140 | that a neuron will release neurotransmitter.

00:46:59.000 | They are sort of a brake on the system.

00:47:00.760 | They are a way of shutting down

00:47:03.100 | the communication between neurons, regulating it,

00:47:06.120 | not to make it completely quiet,

00:47:07.500 | but to adjust the levels with a lot of nuance.

00:47:10.660 | Now, the other thing that the endogenous cannabinoids do

00:47:13.620 | is sort of a mind bender,

00:47:15.420 | because we're talking about cannabis,

00:47:17.300 | and a commonly known feature

00:47:19.620 | of cannabis and marijuana consumption

00:47:21.980 | is disruptions in short-term memory.

00:47:24.020 | And there is essentially zero debate

00:47:26.220 | as to whether or not that occurs,

00:47:27.500 | and we'll talk about the mechanisms a little bit later.

00:47:29.780 | And yet endogenous cannabinoids,

00:47:33.680 | the chemicals that you naturally release

00:47:35.300 | from these postsynaptic neurons

00:47:36.720 | that travel retrogradely back to the presynaptic neuron,

00:47:40.240 | actually can lead to strengthening of connections

00:47:43.820 | between the presynaptic neuron and the postsynaptic neuron

00:47:47.280 | through a process called long-term potentiation, or LTP.

00:47:51.600 | They can also cause what's called depression

00:47:55.140 | of communication between a presynaptic neuron

00:47:57.680 | and a postsynaptic neuron.

00:47:59.980 | Long-term depression has nothing to do

00:48:03.580 | with depression as a psychological state or as a illness.

00:48:07.560 | Long-term potentiation and long-term depression

00:48:11.060 | simply refer to the probability

00:48:12.940 | that one neuron will be able to stimulate

00:48:15.380 | and activate another neuron.

00:48:17.240 | And as I just told you,

00:48:19.680 | the endogenous cannabinoids can either turn up the dial

00:48:23.220 | or turn down the dial.

00:48:24.420 | They can either increase the probability

00:48:26.340 | or decrease the probability

00:48:28.060 | that a given connection between neurons

00:48:30.580 | will function more or will function less.

00:48:33.340 | So if you think about the communication between neurons

00:48:35.060 | as a crosstalk, as a conversation,

00:48:37.860 | well, the endogenous cannabinoids can dictate

00:48:41.580 | whether or not that conversation is likely to occur

00:48:43.900 | or not to occur.

00:48:44.740 | Think of them as either putting someone

00:48:47.380 | at the top of your text chain in your phone,

00:48:50.320 | which would be long-term potentiation,

00:48:52.460 | or essentially blocking their number,

00:48:55.100 | which would essentially be long-term depression.

00:48:58.680 | So if you're getting the impression

00:49:00.880 | that the endogenous cannabinoids

00:49:02.240 | are working in a number of different ways

00:49:04.160 | and it's not very straightforward, you're right.

00:49:06.200 | In fact, that's the message that I'd like you to take away.

00:49:08.420 | The endogenous cannabinoids

00:49:10.260 | are sometimes increasing neuronal communication.

00:49:12.440 | This can lead to increases in mood

00:49:14.440 | or increases in the likelihood

00:49:16.840 | that someone will talk a certain way

00:49:18.380 | or behave a certain way or feel a certain way.

00:49:20.760 | They can also lead to decreases in synaptic transmission,

00:49:24.220 | that is communication between neurons,

00:49:25.760 | in ways that will make somebody's mood lower

00:49:29.180 | or will make them less hungry or more hungry.

00:49:32.380 | And here's the really key thing.

00:49:34.960 | There are two kinds of endogenous cannabinoid receptors

00:49:38.260 | referred to as CB1 and CB2.

00:49:40.940 | And we can say with confidence

00:49:42.960 | that CB1 is highly enriched in the nervous system

00:49:46.620 | and especially within the brain.

00:49:48.160 | It's found not everywhere,

00:49:49.480 | but almost everywhere in the brain

00:49:51.060 | and elsewhere in the nervous system,

00:49:52.180 | so spinal cord and other aspects of the nervous system.

00:49:55.900 | CB2, the cannabinoid receptor.

00:49:58.640 | CB2 is largely located in the tissues of the body,

00:50:02.500 | including the immune system, the liver,

00:50:04.660 | even the genitals, et cetera.

00:50:07.040 | So what this means is that the endogenous cannabinoids

00:50:09.680 | are having these sorts of effects on neurons

00:50:11.880 | that I talked about,

00:50:12.720 | but they are also having effects on immune cells,

00:50:15.660 | on reproductive organs, on liver, on digestion,

00:50:18.420 | on hunger, et cetera,

00:50:19.660 | through mechanisms that are divorced from the function

00:50:22.640 | of the nervous system of neurons.

00:50:24.900 | Now, in reality, no system of the brain and body

00:50:26.860 | is divorced from the nervous system

00:50:28.060 | because the nervous system is controlling everything.

00:50:30.340 | There is really the master controller

00:50:31.620 | and everything's feeding back to the nervous system,

00:50:33.440 | so it's a two-way street.

00:50:34.880 | But the simple way to think about it is CB1 receptors

00:50:38.180 | are mainly in the nervous system

00:50:40.140 | and CB2 receptors are mainly in the body

00:50:42.300 | and endogenous cannabinoids.

00:50:45.020 | Again, EAE, anatomide, and 2AG, arachidinol glycerol,

00:50:50.020 | are impacting CB1 and CB2 receptors.

00:50:53.460 | Today, we're mainly going to talk about CB1 receptors

00:50:55.740 | 'cause they are the ones that are responsible

00:50:57.220 | for most of the familiar effects of cannabis.

00:50:59.780 | But the key takeaway at this point

00:51:02.500 | is to really understand that the major effects

00:51:05.920 | of your endogenous cannabinoids on these receptors

00:51:08.740 | in this particular CB1 are very nuanced.

00:51:12.220 | It depends on context, it depends on which neurons.

00:51:14.260 | It's sometimes increasing communication between neurons,

00:51:17.020 | sometimes decreasing it.

00:51:18.940 | And then along comes cannabis,

00:51:21.260 | and that cannabis, again, can arrive by smoking,

00:51:24.280 | by vaping, by edible.

00:51:26.780 | And cannabis contains THC and CBD

00:51:30.060 | that potently bind the CB1 receptor.

00:51:34.700 | And now the effects of the CB1 receptor

00:51:37.900 | being occupied by THC or being occupied by CBD

00:51:43.660 | are not very nuanced.

00:51:44.860 | In fact, they are very predictable.

00:51:47.500 | And especially important is to understand

00:51:50.120 | that they are so strong and they park in that receptor

00:51:53.220 | with such affinity, with such force and precision

00:51:56.500 | and stubbornness and refusal to leave that receptor

00:51:59.100 | that they completely out-compete

00:52:02.020 | the endogenous cannabinoid system.

00:52:04.100 | In fact, they leave the endogenous cannabinoid system

00:52:06.440 | essentially dysfunctional,

00:52:08.440 | which in some cases may be a good thing,

00:52:10.920 | but in most cases is going to lead to problems

00:52:14.280 | of various kinds.

00:52:15.120 | And we'll talk about what sorts of problems.

00:52:16.520 | And again, I feel obligated to say,

00:52:19.120 | this is not me saying don't ingest cannabis or THC or CBD.

00:52:23.220 | That's not what I'm saying.

00:52:24.400 | What I'm saying is if you evaluate the potency,

00:52:28.000 | that is in technical terms,

00:52:29.440 | it would be the affinity with which these compounds,

00:52:32.520 | THC and CBD and CBN bind to these endogenous receptors,

00:52:37.240 | that would be like a howitzer gun,

00:52:38.820 | like a cannon going off as compared to endogenous cannabinoid

00:52:43.820 | whether or not it's EAE or 2AG,

00:52:46.580 | which is more like a cap gun level of activation,

00:52:49.700 | at least in this analogy.

00:52:50.980 | So now you have what at least I would like to think

00:52:53.700 | is a fairly complete understanding

00:52:55.620 | of the different varieties of cannabis,

00:52:57.780 | at least at a broad sweep

00:53:00.360 | and the different biological effects that they can have,

00:53:03.100 | at least in terms of the major receptors

00:53:04.860 | and in retrograde signaling, et cetera, et cetera.

00:53:07.940 | Now let's take a step back into the real world

00:53:10.500 | and evaluate or think about what happens

00:53:13.140 | when somebody smokes cannabis or ingest cannabis

00:53:17.660 | by way of edible or tincture or something of that sort.

00:53:20.460 | Cannabis is very fast to enter the bloodstream.

00:53:25.400 | In fact, within 30 seconds,

00:53:28.940 | it's going to enter the brain

00:53:30.060 | and permeate throughout the brain and body.

00:53:32.320 | That's very, very fast.

00:53:33.720 | I mean, we contrast that with something like alcohol

00:53:36.280 | or even nicotine, depending on how the nicotine is delivered,

00:53:39.160 | that is a very fast delivery of the psychoactive

00:53:42.560 | and biologically active compound,

00:53:44.340 | which in this case is THC and CBD

00:53:46.480 | and probably some other things as well.

00:53:48.780 | So within 30 seconds,

00:53:49.920 | it reaches the brain and bodily tissues

00:53:52.920 | and within 30 to 60 minutes,

00:53:56.140 | it's going to reach its peak concentrations

00:53:58.620 | and have its peak biological effects.

00:54:00.920 | Those aren't always the same thing,

00:54:01.940 | but in the case of cannabis,

00:54:03.660 | and again, here I'm using cannabis

00:54:04.780 | as a kind of an umbrella term for THC and CBD,

00:54:07.520 | the effects are going to peak at about 30 to 60 minutes

00:54:10.700 | after bringing those compounds into the body

00:54:13.360 | in some way or another.

00:54:15.040 | And the effects tend to last

00:54:16.360 | anywhere from three to four hours,

00:54:17.980 | although there's some variation on that

00:54:19.720 | depending on individual metabolism,

00:54:21.860 | whether or not somebody is familiar with the compound,

00:54:26.340 | believe it or not, psychologically familiar,

00:54:27.800 | but also biologically familiar,

00:54:29.480 | or whether or not it's a first time use

00:54:30.780 | or occasional use and so on.

00:54:33.800 | THC and CBD and other components of cannabis

00:54:37.660 | are highly what we call lipophilic.

00:54:39.560 | That is they have an affinity toward

00:54:42.360 | and they can actually pass through fatty tissues.

00:54:44.480 | Now, every cell in your body,

00:54:45.560 | but especially neurons have a double layer of fat

00:54:48.860 | on their outside.

00:54:49.960 | And of course, when people hear fat,

00:54:51.800 | they always think, "Ooh, fat's bad, fat's whatever."

00:54:54.100 | Most of the world seems to want to lose fat or bodily fat.

00:54:57.000 | Here we're talking about the fatty membrane,

00:54:59.840 | the barrier around each tissue.

00:55:01.600 | In this case, we're talking particularly about neurons.

00:55:04.400 | And THC and CBD and the other components of cannabis

00:55:08.740 | are highly lipophilic.

00:55:10.040 | So they can get into essentially all cells

00:55:11.920 | just simply by flowing into them.

00:55:13.720 | They will also remain in those cells for a long time.

00:55:17.000 | So I know that a number of people,

00:55:19.320 | depending on whether or not they get tested for work

00:55:21.920 | or for sport or otherwise for cannabis or CBD and THC,

00:55:26.320 | don't take this as a strict number,

00:55:28.980 | but typically if one ingests CBD or THC,

00:55:33.980 | smokes cannabis, ingests orally, et cetera,

00:55:36.900 | it doesn't matter.

00:55:37.740 | It's going to stay in that fatty tissue and can be detected

00:55:40.900 | for at least as long as 80 days after ingestion.

00:55:43.740 | And there's a whole industry as to

00:55:45.780 | how to accelerate the clearance.

00:55:47.880 | And I should just tell you that just losing bodily fat

00:55:51.280 | isn't going to eliminate it from your system,

00:55:54.360 | maybe partially in those fat cells,

00:55:56.420 | but certainly intravisceral fat and other fatty tissue

00:56:00.420 | that's in and around the brain and body

00:56:02.380 | is going to harbor that THC molecule and the CBD molecule

00:56:06.700 | for quite a long while, at least 80 days.

00:56:09.060 | Okay, so if someone smokes cannabis

00:56:12.160 | or they ingest cannabis,

00:56:13.740 | very rapidly gets into the bloodstream

00:56:16.400 | and the components that are psychoactive

00:56:18.160 | get into the bloodstream

00:56:19.200 | and are immediately able to access neurons and other cells

00:56:23.560 | and start having these effects of parking

00:56:25.020 | at those endogenous cannabinoid receptors

00:56:27.220 | and impacting the signaling between neurons,

00:56:29.480 | which leads to the subjective effects of cannabis,

00:56:33.980 | including THC and CBD.

00:56:35.300 | So let's talk about

00:56:36.140 | what those different subjective effects are.

00:56:38.540 | Again, this is going to vary depending on whether or not

00:56:40.480 | people are ingesting sativa varieties of cannabis.

00:56:44.700 | Just to remind you, those tend to be elevated.

00:56:47.140 | Mood, alertness, talkativeness,

00:56:48.980 | people who take sativa varieties tend to talk a lot more

00:56:51.740 | than they would otherwise.

00:56:53.380 | Again, there are exceptions to this.

00:56:54.820 | Of course, there are exceptions.

00:56:56.020 | I'm sure there are people out there shouting,

00:56:57.360 | although I guess if you're the quiet people

00:56:58.620 | who don't talk too much, you're probably not shouting,

00:57:00.460 | or if you're not, you're not doing it on sativa.

00:57:02.900 | Joke intended, but in any event, there are exceptions,

00:57:05.940 | but there are also general rules.

00:57:07.720 | And the sativas tend to meet people sort of mood elevated,

00:57:10.060 | energetic, again, the sort of head high,

00:57:13.040 | and indica varieties tend to do the opposite,

00:57:16.500 | more of a sedative, relaxant, et cetera.

00:57:19.900 | Why and how would they do that?

00:57:21.720 | Okay, without going into an extensive deep dive

00:57:24.300 | into the different neurotransmitter systems

00:57:25.840 | of the brain and body, what we know for sure

00:57:28.600 | is that CB1 receptors are present on an enormous number

00:57:32.320 | of different neurons and brain structures

00:57:33.980 | and neural circuits so that the sativa varieties

00:57:37.980 | that act as sort of a stimulant, making people feel happy,

00:57:42.820 | 'cause in general, they do tend to elevate mood,

00:57:45.420 | at least at certain dosages.

00:57:47.460 | Talkative tend to make people feel like they have ideas

00:57:51.920 | that are interesting, that they might want to share,

00:57:54.500 | tend to narrow their context, so tend to increase focus.

00:57:57.260 | This is something that's not often discussed about cannabis,

00:57:59.420 | but it can, especially the sativa varieties

00:58:01.280 | can increase people's level of focus to particular things,

00:58:04.380 | something they're watching or something they're doing,

00:58:06.260 | or music allows them to narrow their sense of focus.

00:58:08.860 | That's going to occur by activation of CB1 receptors

00:58:13.420 | in the so-called prefrontal cortex,

00:58:14.900 | which is just behind the forehead.

00:58:16.540 | And the prefrontal cortex acts as a strong modulator

00:58:19.860 | of so-called limbic circuitry and other circuitry

00:58:22.580 | that is more stress-oriented.

00:58:24.560 | The way to think about the stress and limbic circuitry,

00:58:27.960 | such as the amygdala, which many people have heard about,

00:58:30.360 | is that they aren't really circuits for fear and stress.

00:58:33.200 | They are circuits that are constantly evaluating

00:58:35.360 | one's own internal state, heart rate, et cetera,

00:58:38.240 | and what's happening externally.

00:58:40.200 | And sorry to say, but the default of those systems

00:58:43.360 | is to detect danger, the sort of threat detection systems.

00:58:46.360 | And then the prefrontal cortex largely acts

00:58:48.500 | as a brake on those systems,

00:58:50.300 | sort of like the reins pulling back on a steed of horses

00:58:53.140 | that would otherwise just kind of take off.

00:58:55.440 | And so the sativa varieties tend to increase CB1 activation

00:58:59.280 | in the prefrontal cortex and in other circuitry

00:59:02.080 | that then leads to a kind of overall reduction in stress

00:59:05.220 | because of the way that prefrontal circuitry

00:59:06.660 | can reduce activation of the amygdala.

00:59:09.220 | Now that of course does not explain

00:59:11.540 | why some people become very stressed and very paranoid

00:59:14.520 | when they smoke sativa varieties

00:59:16.160 | or other varieties of cannabis or ingest other varieties

00:59:18.940 | of cannabis.

00:59:19.780 | We will talk about the paranoid effect and why that occurs

00:59:22.520 | and who might predict that would occur to them

00:59:25.200 | in a little bit.

00:59:26.720 | But I just want to give you a sense of how this is working

00:59:28.920 | because as I mentioned before,

00:59:31.320 | THC and/or CBD are going to bind that CB1 receptor,

00:59:34.860 | let's say in prefrontal cortex

00:59:36.060 | and neurons of prefrontal cortex is going to bind there.

00:59:38.360 | And then there'll be a retrograde signaling

00:59:40.320 | back to the presynaptic neuron.

00:59:41.640 | And in the case of prefrontal cortex,

00:59:43.420 | what's happening is it's increasing transmission,

00:59:46.420 | increasing the release of neurotransmitter

00:59:48.100 | in prefrontal cortex.

00:59:49.700 | However, at the same time,

00:59:51.460 | the very same THC and CBD that was brought into the system

00:59:56.500 | is binding the very same type of receptors,

00:59:59.060 | CB1 receptors in other brain structures

01:00:01.260 | such as the amygdala

01:00:02.340 | and causing retrograde signaling

01:00:05.780 | back to the presynaptic neurons in the amygdala,

01:00:09.160 | but it's quieting the activation of those neurons.

01:00:13.260 | So this is interesting, right?

01:00:14.440 | We have the same compounds, THC and/or CBD

01:00:18.220 | brought into the body and brain,

01:00:20.860 | binding the same receptors,

01:00:22.880 | in this case, the CB1 receptors,

01:00:25.180 | but depending on where those receptors are located

01:00:28.460 | and which brain areas we're referring to,

01:00:31.100 | they are either causing heightened levels

01:00:34.740 | of alertness and activation of systems

01:00:37.860 | that are designed to make you talkative

01:00:39.500 | and alertness and mood, et cetera, focus,

01:00:42.220 | or they are causing suppression of those circuitries.

01:00:45.700 | So we have kind of a seesaw effect here

01:00:47.680 | where the same compound is increasing mood and alertness

01:00:49.900 | and focus in the prefrontal cortex

01:00:51.220 | and is decreasing stress and threat detection

01:00:54.500 | in the amygdala.

01:00:55.980 | And that's one of the reasons why,

01:00:57.380 | especially the sativa varieties of cannabis,

01:01:00.340 | allow people to enter these states of focus.

01:01:02.760 | Some might even say flow,

01:01:03.940 | although I don't want to go into

01:01:05.780 | what flow states really are,

01:01:07.380 | that's for a different discussion

01:01:09.180 | and it's very poorly defined as it is.

01:01:12.580 | And I certainly don't want to give people the impression

01:01:14.340 | that cannabis increases flow states

01:01:16.060 | because that's not always the case

01:01:18.620 | and certainly most often is not going to be the case.

01:01:21.020 | But the idea here is that this molecule

01:01:23.100 | comes into our brain and is shifting everything

01:01:26.060 | towards a state of focus, elevated mood,

01:01:29.220 | of heightened sense of importance

01:01:30.900 | about whatever it is that we happen to be doing.

01:01:32.820 | And now of course, whatever we could happen to be doing

01:01:35.380 | could be writing a song, writing poetry,

01:01:39.180 | communicating with somebody,

01:01:40.540 | but it could also be something as trivial

01:01:42.240 | as watching cartoons or watching a movie,

01:01:45.820 | which is not trivial in its own right,

01:01:48.100 | but in terms of thinking about the creative aspects

01:01:50.860 | or the creativity stimulating aspects of cannabis

01:01:54.220 | and not sort of productivity oriented.

01:01:57.000 | So narrowed focus, elevated mood,

01:01:59.020 | more relaxed and yet energetic.

01:02:01.200 | That's the major effects of the sativa varieties, except,

01:02:05.220 | and this is a really big, bold face, triple underlined,

01:02:07.860 | except in some individuals, depending on dosage,

01:02:12.320 | but also depending on preexisting neural circuitry

01:02:16.340 | and propensity for anxiety,

01:02:18.240 | some people ingest or smoke sativa varieties

01:02:21.980 | and regardless of whether or not it's a type one,

01:02:23.920 | type two or type three variety, okay?

01:02:25.940 | Regardless of the ratio between THC and CBD,

01:02:29.140 | people will experience intense anxiety and paranoia.

01:02:33.900 | Now, how do you predict?

01:02:35.620 | Who will experience intense anxiety and paranoia

01:02:38.180 | and who will experience intense relaxation, focus

01:02:41.700 | and sense of creativity from ingesting or smoking

01:02:45.220 | a type one, type two or type three sativa?

01:02:47.920 | Well, there is no way to predict that.

01:02:50.540 | And there's a lot of kind of what I would call street lore

01:02:52.980 | or dorm room lore or kind of peer, not peer reviewed,

01:02:57.860 | but sort of peer discussed.

01:03:00.420 | I mean, among friends and people and acquaintances lore

01:03:03.620 | out there that what one needs to do is simply smoke more,

01:03:07.440 | right, or just ingest more, you hear that.

01:03:09.500 | Oh, well, listen, if it makes you paranoid,

01:03:11.040 | you simply need to use more.

01:03:12.340 | That is absolutely categorically false.

01:03:14.820 | Everything we know about the way that THC and CBD work

01:03:18.160 | is that they tend to potentiate,

01:03:20.020 | that is increase the effects of these different systems

01:03:25.020 | at given synapses and in different areas

01:03:27.260 | of the brain and body.

01:03:28.100 | That is if someone experiences paranoia or anxiety

01:03:32.860 | from a given strain of the marijuana plant

01:03:37.100 | or from ingesting an edible in a particular way

01:03:39.260 | or a particular kind of edible,

01:03:40.780 | that person is very likely to experience the same effect

01:03:44.820 | every time they ingest that strain or variety.

01:03:47.400 | This is part of what's led to this enormous industry.

01:03:51.980 | I mean, there are a number of different reasons,

01:03:53.080 | but this is part of what's led to this enormous industry

01:03:55.220 | of highly customized cannabis,

01:03:58.500 | where people will spend some time really seeking out

01:04:01.040 | the different strains of cannabis and hybrids of cannabis

01:04:05.380 | that work best for them

01:04:06.980 | and work best for them in particular context.

01:04:09.660 | I wish I could tell you that if you are a person who is,

01:04:13.340 | you know, between five foot seven and six feet tall,

01:04:16.280 | and you have blue eyes or brown eyes,

01:04:19.400 | that the sativa varieties are going to be right for you

01:04:21.780 | or that the sativa varieties

01:04:23.060 | are going to give you panic attacks, I can't do that.

01:04:25.440 | The only way to determine it would be to actually experience

01:04:28.860 | ingesting those or smoking those,

01:04:30.160 | which is certainly also not what I'm suggesting, right?

01:04:32.420 | That's up to you.

01:04:33.260 | I'm not telling you what to do or what not to do,

01:04:35.180 | but there are no good predictors.

01:04:36.980 | In fact, if you look in the literature,

01:04:39.920 | it is not at all clear

01:04:41.100 | that people who have a heightened level of anxiety

01:04:44.420 | when they do not smoke cannabis

01:04:46.980 | will experience cannabis as less paranoia inducing

01:04:51.980 | or more relaxing.

01:04:53.220 | That's simply not the case.

01:04:55.180 | Now, what we can say for sure

01:04:57.900 | is that general categories of effects

01:05:00.740 | such as increased focus and reduced anxiety

01:05:03.580 | are largely due to activation of areas

01:05:05.420 | like the prefrontal cortex.

01:05:06.860 | Now, unlike other compounds like nicotine or alcohol

01:05:10.180 | or neurotransmitter systems like dopamine,

01:05:12.160 | when we talk about the cannabinoid system,

01:05:14.400 | and I say effects, biological effects, psychoactive effects,

01:05:18.960 | I want you to keep in mind always, please, please, please,

01:05:21.640 | keep in mind that those effects can be varied

01:05:25.480 | and often opposite in direction.

01:05:28.660 | So let's just give an example of that.

01:05:30.860 | I just mentioned that when people smoke or eat sativa,

01:05:34.780 | that it tends to lead to one specific set of,

01:05:37.660 | or generally leads to one specific set of effects,

01:05:40.540 | heightened focus, mood, et cetera.

01:05:41.920 | Whereas when they ingest or smoke indica

01:05:45.620 | and its components, right?

01:05:47.320 | Again, we're still talking about THC and CBD

01:05:49.860 | in varying ratios, but now indica cannabis,

01:05:53.580 | and you say, well, why would it improve

01:05:56.220 | the transition time to sleep?

01:05:58.140 | Or at least give people the impression

01:05:59.480 | that it improved the transition time to sleep.

01:06:01.020 | We'll talk about what indica actually does for sleep

01:06:03.200 | in a little bit.

01:06:04.420 | But indica also tends to suppress activation

01:06:07.360 | of the amygdala and threat detection centers in the brain.

01:06:09.600 | Again, binding the same CB1 receptors

01:06:11.560 | and those retrograde signaling mechanisms

01:06:13.640 | that talked about before.

01:06:15.100 | But it also tends to shut down the hippocampus,

01:06:18.320 | an area of the brain associated with memory,

01:06:21.720 | which is why indica varieties lead to pronounced,

01:06:26.040 | or I should say profound defects in short-term memory

01:06:29.400 | and sometimes in long-term memory as well

01:06:31.020 | if it's consumed over long periods of time.

01:06:33.880 | We'll talk about short, medium and long-term consumption,

01:06:36.220 | occasional consumption going forward.

01:06:38.000 | So what I'd like you to take away

01:06:39.060 | from this component of the discussion is,

01:06:40.860 | first of all, the mechanism of action

01:06:43.900 | by which cannabis impacts the brain and body,

01:06:48.260 | but in particular, the brain is going to be

01:06:49.680 | through CB1 receptors and those CB1 receptors

01:06:52.420 | can lead to either an acceleration or a break

01:06:55.000 | on particular biological mechanisms.

01:06:56.680 | And there are going to be a constellation

01:06:59.600 | of different accelerations and breaking

01:07:01.960 | of different neural systems in the brain and body,

01:07:05.160 | depending on whether or not people ingest sativa

01:07:07.920 | or indica or some hybrid strain.

01:07:10.360 | And perhaps most importantly,

01:07:11.860 | even if you didn't understand anything that I've said

01:07:13.620 | about the biology of these different strains

01:07:15.360 | and the receptors, please do understand

01:07:17.520 | that there is no way to predict what the effect

01:07:21.720 | of a given strain will be on an individual.

01:07:24.340 | There has been extensive exploration

01:07:26.720 | as to whether or not people who are so-called mellower

01:07:29.340 | or more anxious or any number

01:07:32.280 | of different personality dimensions will respond

01:07:35.240 | in one way or the other.

01:07:36.120 | But in fact, there is no way to tell.

01:07:38.580 | Layer on top of that, the fact that dosing THC and CBD

01:07:43.240 | can be fairly straightforward in the form of edibles, right?

01:07:46.320 | Because there can be, at least if it's a controlled source,

01:07:50.240 | a defined number of milligrams of THC,

01:07:53.560 | a defined number of milligrams of CBD.

01:07:55.960 | That's true for ingestibles.

01:07:57.920 | It's much harder to gauge that

01:08:00.120 | from the smokable forms of cannabis,

01:08:02.560 | especially if those smokable forms of cannabis

01:08:04.440 | are obtained through sources

01:08:05.680 | where there isn't a lot of clear information

01:08:08.160 | about the total amount of THC in that product.

01:08:11.260 | Now, this is all changing quite a lot nowadays

01:08:13.280 | because of the commercialization of THC and CBD products

01:08:17.520 | and cannabis in a number of different areas,

01:08:19.520 | including in the United States.

01:08:21.220 | But still many people are ingesting cannabis, THC, CBD

01:08:24.960 | through sources where they don't really know

01:08:26.200 | how much they're bringing into their system.

01:08:28.040 | And so whether or not someone

01:08:30.160 | gets incredible anxiety relief,

01:08:32.880 | enhanced sense of mood and focus and wellbeing,

01:08:35.820 | pain relief, et cetera,

01:08:37.060 | or whether or not they have full-blown panic attacks,

01:08:39.640 | et cetera, is very hard to predict

01:08:42.920 | based on dosage information alone.

01:08:45.200 | Now, of course, we can create broad categories,

01:08:47.700 | and we were going to talk about studies

01:08:48.900 | that create broad categories of low dose,

01:08:50.880 | moderate dose, and high dose,

01:08:52.660 | frequent use and infrequent use.

01:08:54.920 | But unlike alcohol, unlike nicotine,

01:08:57.740 | we can't really point to specificity

01:09:00.620 | of X amount of alcohol, grams of alcohol per week,

01:09:04.720 | which is safe, or X amount of alcohol, which is not safe.

01:09:07.720 | And so I know a lot of people out there are wondering,

01:09:10.220 | how often can they smoke cannabis?

01:09:13.260 | Or how often can they eat cannabis or THC or CBD

01:09:16.860 | in any number of its different forms and products safely?

01:09:21.220 | Well, we have to really define what safely means,

01:09:23.740 | and we have to really acknowledge

01:09:25.240 | that there's a pretty loose set of controls

01:09:29.420 | over what one is bringing into their brain and body

01:09:32.500 | as they ingest THC and CBD.

01:09:35.180 | But even under conditions in which it's very controlled,

01:09:38.440 | it's very hard to predict what those effects will be.

01:09:41.040 | So before moving into specifics of taking cannabis

01:09:44.940 | or not taking cannabis, who should, who shouldn't,

01:09:46.740 | what the medicinal purposes are,

01:09:49.180 | and what some of the newer exciting data point to,

01:09:52.580 | I just briefly want to make a list,

01:09:53.900 | and I promise very briefly, I know I'm not often concise,

01:09:56.660 | but I do try to be thorough for your sake.

01:09:59.380 | I want to make a very brief list

01:10:01.640 | of the different brain areas that are impacted by THC and CBD

01:10:06.580 | and why THC and CBD have the various effects they do.

01:10:10.160 | When somebody smokes or ingests cannabis,

01:10:17.320 | doesn't matter what the THC or CBD ratio is,

01:10:21.480 | if they experience deficits in memory,

01:10:26.720 | and that's almost always present,

01:10:28.940 | that's going to be because of reductions

01:10:31.720 | in electrical activity within this brain region

01:10:33.740 | we call the hippocampus, okay?

01:10:35.400 | Hippocampus means seahorse, it's shaped like a seahorse,

01:10:37.580 | anatomists like to name things after what things look like,

01:10:40.400 | but hippocampus memory is reduced

01:10:43.420 | in particular short-term memory.

01:10:45.000 | That's true regardless of whether or not

01:10:46.820 | one is using sativa, indica, or some hybrid.

01:10:50.980 | In general, the prefrontal cortex

01:10:55.860 | is going to be activated by the sativa varieties,

01:10:58.540 | which is going to increase thinking

01:11:00.060 | and narrowly constrain focus to some activity,

01:11:04.240 | and that's more commonly associated

01:11:05.680 | with the sativa varieties.

01:11:07.040 | The indica varieties, as I mentioned before,

01:11:09.160 | tend to lead to a suppression of activity

01:11:11.200 | in prefrontal cortex, believe it or not,

01:11:13.440 | and turn off thinking and planning.

01:11:15.640 | This is why indica varieties are often used for relaxation

01:11:20.360 | and for promoting sleep.

01:11:21.920 | Regardless of whether or not sativa or indica variety,

01:11:26.420 | and again, regardless of the ratio of THC to CBD,

01:11:30.760 | there is a general suppression of neural circuits

01:11:33.760 | within the so-called basal ganglia and cerebellum.

01:11:35.960 | Basal ganglia and cerebellum are areas of the brain

01:11:38.520 | that are involved in action planning and withholding action,

01:11:41.120 | so that would be the basal ganglia,

01:11:42.280 | so-called go/no-go circuitry,

01:11:44.800 | and the cerebellum, which is involved in balance,

01:11:47.400 | but also motor planning and motor sequencing.

01:11:50.020 | This is why people who smoke marijuana,

01:11:54.700 | regardless of the strain,

01:11:57.040 | will tend to be less physically mobile.

01:12:00.000 | Other common effects are reddening of the eyes,

01:12:02.520 | dryness of the mouth.

01:12:03.440 | That's actually caused by the same general mechanism,

01:12:06.280 | which is a reduction in the secretion of saliva

01:12:09.320 | and of sort of tears and lubrication of the eyes

01:12:12.420 | from the lacrimal glands of the eyes

01:12:14.180 | because of the presence of largely CB2,

01:12:17.760 | but also CB1 receptors in the mouth and on the eyes.

01:12:21.380 | And there tends to be,

01:12:23.340 | especially with certain strains of cannabis,

01:12:26.040 | increase in appetite, so-called munchies,

01:12:28.840 | and that has everything to do with very, very high density

01:12:33.420 | of CB1 receptors in the hypothalamus,

01:12:35.600 | and in particular areas of the hypothalamus,

01:12:37.360 | like the arcuate nucleus of the hypothalamus,

01:12:39.860 | other areas as well, of course,

01:12:41.640 | that have tons of CB1 receptors, bind THC and CBD,

01:12:46.440 | and activate the neurons that strongly stimulate appetite

01:12:49.760 | through two mechanisms.

01:12:51.260 | One is a cognitive mechanism of creating a preoccupation

01:12:55.140 | with food and anticipation of taste,

01:12:58.000 | as well as the experience of taste,

01:12:59.840 | so the narrowing of focus to what you want to go eat,

01:13:04.260 | you really crave, I don't know, pizza,

01:13:06.880 | it seems to be high fat, high carbohydrate foods,

01:13:08.680 | but really crave pizza and narrowing of focus

01:13:13.680 | so that you're not thinking about anything else,

01:13:15.160 | but also signaling from the hypothalamus to the gut,

01:13:18.920 | to neurons within the stomach itself

01:13:21.320 | that regulate blood sugar.

01:13:23.040 | So there are strong effects on blood sugar of THC and CBD

01:13:27.820 | that generally lead to increases in appetite.

01:13:29.960 | So two parallel mechanisms, one within the brain,

01:13:32.680 | one within the body, increasing appetite.

01:13:34.900 | So there's an array of different effects.

01:13:36.320 | And as I mentioned before,

01:13:37.600 | CB1 receptors are present all over the nervous system

01:13:41.100 | in the brain, the spinal cord.

01:13:42.200 | In fact, the presence of CB1 receptors in the spinal cord

01:13:44.920 | largely explains the fact that THC and CBD,

01:13:48.300 | to some extent, although it's not very well studied,

01:13:50.360 | can provide some pain relief.

01:13:52.420 | I say some because a lot of people perceive

01:13:55.760 | or believe that they experience more pain relief

01:13:58.480 | from cannabis than they actually do.

01:14:00.680 | It actually has a lot to do with a perceptual shift

01:14:03.260 | to basically focusing on other things,

01:14:04.920 | but there does seem to be some anti-nociceptive,

01:14:08.360 | meaning anti-pain effects of cannabis, THC in particular,

01:14:13.000 | and that is exerted largely through effects

01:14:15.400 | on CB1 receptors in neurons of the spinal cord.

01:14:19.700 | So a broad array of effects are taking place,

01:14:21.960 | regardless of what strain you take

01:14:23.300 | and whether or not you eat the cannabis

01:14:25.500 | or you smoke the cannabis.

01:14:26.960 | And the broad array of effects can be explained by the fact

01:14:30.000 | that that retrograde signaling can lead to activation

01:14:32.240 | or suppression of activity in various neurons.

01:14:34.920 | So now I'd like to take a step back

01:14:36.520 | from the biology of cannabis and THC and CBD

01:14:39.040 | and all the signaling and receptors, et cetera,

01:14:41.000 | and really just focus on cannabis use.

01:14:44.120 | And wherever possible,

01:14:45.280 | I will point to the specific strains that have been studied

01:14:48.680 | and the ratios of THC to CBD.

01:14:51.200 | But I have to say that unfortunately,

01:14:54.260 | most studies of marijuana of cannabis,

01:14:57.460 | while they have been very careful

01:14:59.800 | to detail the amount of THC,

01:15:02.440 | low dose, medium dose, or high dose,

01:15:03.960 | and actually getting very specific,

01:15:05.060 | right down to the number of milligrams

01:15:06.320 | or even how much circulating THC is present

01:15:08.280 | after somebody smokes a joint or ingests cannabis,

01:15:13.280 | most studies have not distinguished

01:15:15.960 | between sativa and indica strains.

01:15:19.880 | And that's unfortunate because in the real world,

01:15:22.160 | people are distinguishing between sativa and indica strains

01:15:25.420 | in their patterns of use and what they prefer

01:15:27.240 | and what they don't prefer,

01:15:28.120 | even what they prefer to smoke during the day

01:15:30.280 | or ingest during the day versus night.

01:15:31.640 | Believe it or not, there are people

01:15:32.480 | who are using certain strains during the day

01:15:34.860 | and other strains at night.

01:15:36.220 | But the science is yet to catch up to that.

01:15:39.640 | Or I should say more accurately,

01:15:42.760 | the general public and the themes that are emerging

01:15:45.380 | and the practices that are emerging around cannabis,

01:15:47.960 | especially in states where it's decriminalized or legalized,

01:15:51.240 | are occurring at such a rapid rate

01:15:52.600 | that there's absolutely no way

01:15:53.800 | that the science could keep up.

01:15:55.120 | This is a naturally occurring experiment.

01:15:57.200 | Not to say that it's natural, like people should do it,

01:15:59.080 | but it's an experiment that's happening in real time

01:16:01.160 | in the real world,

01:16:02.100 | much faster than controlled studies

01:16:05.080 | within university laboratories

01:16:06.360 | and other laboratories can keep up.

01:16:07.920 | So at this point, I think it's appropriate to ask ourselves,

01:16:10.680 | why do people even use cannabis?

01:16:12.760 | I mean, what are they trying to achieve?

01:16:14.060 | Is it always about not feeling pain?

01:16:16.380 | Is it always about reducing anxiety?

01:16:18.360 | Well, sometimes it is,

01:16:19.260 | but oftentimes people are using cannabis

01:16:21.520 | in order to achieve a particular state.

01:16:23.840 | And we could use a broad brush and say,

01:16:25.960 | well, they just like being high,

01:16:27.940 | but while that may be true in a lot of circumstances,

01:16:30.680 | and I have to believe it actually is true

01:16:33.260 | in a lot of circumstances,

01:16:34.560 | there are a lot of people who use cannabis

01:16:37.900 | in a very directed way,

01:16:39.480 | or they get quote unquote high in order to achieve states

01:16:43.020 | that to them are particularly attractive.

01:16:45.460 | And one such state is a state of creativity.

01:16:49.080 | And this brings us to a broader theme,

01:16:51.080 | which is does cannabis increase creativity?

01:16:54.360 | And if so, is it the THC, the CBD?

01:16:56.720 | What's the appropriate ratio

01:16:58.080 | or the best ratio for accessing creativity?

01:17:00.880 | This is an interesting and important discussion, I believe,

01:17:02.840 | because creativity is one of the more sought after

01:17:05.880 | and more elusive states that humans can experience.

01:17:08.800 | And yet, if you look at human evolution,

01:17:11.200 | you look at our progression

01:17:12.960 | in terms of technology development and culture

01:17:16.000 | and music and poetry, et cetera,

01:17:19.400 | we really can look to creativity as the state

01:17:21.680 | that fostered so much of that evolution.

01:17:24.580 | So whether or not you're into technology

01:17:26.460 | or you're into art or music,

01:17:28.200 | whether or not you're just somebody

01:17:29.440 | who wants to expand their understanding

01:17:31.800 | or their experience of life in some way,

01:17:33.700 | creativity is a fundamentally important state

01:17:37.140 | to try and access and to try and access regularly

01:17:39.440 | and to try and tap into

01:17:40.720 | in order to eventually produce something,

01:17:43.360 | in order to create something of meaning that exists,

01:17:45.560 | not just in that creative state, but to yourself

01:17:48.840 | after that creative state has gone away, right?

01:17:50.960 | So the painting that you paint in the creative state

01:17:52.880 | hopefully is a painting that still inspires

01:17:55.040 | and has impact after you exit that creative state

01:17:58.340 | and that will inspire others.

01:17:59.800 | And this could be true for any number of different things,

01:18:01.840 | not just painting.

01:18:03.220 | So does cannabis increase creativity?

01:18:06.080 | The short answer is it depends.

01:18:08.420 | First of all, we need to define creativity, right?

01:18:10.600 | Here we are as thinking as scientists,

01:18:12.780 | if not already scientists.

01:18:14.560 | And there are basically two modes of thinking

01:18:17.320 | that are associated with creativity

01:18:18.720 | and they don't completely explain creativity.

01:18:21.420 | But if you look in the research, the psychology research

01:18:23.760 | and the neuroscience research,

01:18:25.300 | you'll hear about convergent thinking

01:18:28.400 | and divergent thinking.

01:18:29.680 | Convergent thinking is taking loose ideas

01:18:34.380 | and kind of braiding them together,

01:18:36.680 | finding a common thread,

01:18:38.840 | synthesizing and organizing those different ideas

01:18:41.920 | into some common or specific framework

01:18:45.200 | in order to get or create some specific outcome.

01:18:49.140 | So convergent thinking is basically the person in the room

01:18:53.340 | who's listening to all the ideas and taking them all in.

01:18:56.860 | Maybe it's a panel of how should we get a certain product

01:19:01.860 | out to market or what are the different motifs

01:19:06.060 | that we should include in a piece of music?

01:19:07.840 | Or what should we do in terms of re-architecting

01:19:12.360 | a given physical space,

01:19:14.080 | taking in those different opinions,

01:19:15.560 | those different ideas from different people,

01:19:17.520 | and then synthesizing them and coming up with one

01:19:21.240 | or a small subset of coherent ideas

01:19:23.440 | that incorporate some or all of the ones that they heard.

01:19:26.080 | Okay, so that's convergent thinking.

01:19:27.360 | It doesn't have to involve a panel of people talking to you.

01:19:31.240 | I use that as an example of what goes on

01:19:33.640 | inside your own head

01:19:34.480 | when you are engaging in convergent thinking.

01:19:36.200 | You're thinking, well, so-and-so said this, and I think that,

01:19:39.600 | and you're kind of braiding them through

01:19:40.680 | and trying to get some common theme,

01:19:43.200 | some common vector to emerge from that.

01:19:45.960 | Divergent thinking, on the other hand,

01:19:48.320 | is best described as brainstorming.

01:19:50.440 | It's exploring ideas and continuing to move

01:19:53.120 | into the variation and the vastness of ideas

01:19:56.840 | in hopes of eventually being able to converge

01:19:59.000 | on some novel idea or framework, okay?

01:20:01.640 | So these are similar and related,

01:20:03.080 | but typically the creativity process

01:20:04.960 | involves first brainstorming and divergent thinking,

01:20:08.960 | and then in order to arrive at something,

01:20:11.240 | to actually create something, right?

01:20:12.960 | The verb create, not just thinking about

01:20:15.680 | what you might create, which occurs during divergent thinking

01:20:18.380 | but actually creating something, a specific painting,

01:20:21.200 | a specific song, a specific body of literature,

01:20:25.480 | a specific scientific project or experiment, and so on.

01:20:28.580 | That usually involves convergent thinking.

01:20:32.920 | Now, these can be explored in the laboratory,

01:20:35.600 | and they can be explored in the laboratories

01:20:37.240 | through sets of different types of questionnaires

01:20:39.240 | or even tasks that you can give human subjects,

01:20:41.200 | and this has been done extensively.

01:20:43.280 | And across the entire body of data,

01:20:47.000 | and by that I mean literally hundreds of studies

01:20:49.740 | that have explored the relationship

01:20:50.900 | between particular neural circuits and neurochemicals,

01:20:53.120 | convergent and divergent thinking,

01:20:55.720 | we can arrive at a principle.

01:20:57.680 | And the principle involves a molecule

01:21:01.140 | that many of you have heard about before, which is dopamine.

01:21:03.220 | Dopamine is a neuromodulator.

01:21:04.480 | It's involved in motivation,

01:21:06.160 | and it tends to direct our attention to things outside of us,

01:21:08.960 | but it's also closely related to convergent thinking

01:21:12.140 | and divergent thinking and to the creative process.

01:21:15.060 | And therefore, it should come as no surprise

01:21:17.620 | that diseases of the nervous system, excuse me,

01:21:21.020 | such as bipolar disorder,

01:21:22.980 | which we've done an episode all about bipolar disorder,

01:21:25.800 | or schizophrenia, or mood disorders

01:21:29.720 | that impact the levels of dopamine,

01:21:31.760 | either make it way, way too high or way, way too low,

01:21:35.860 | strongly impact whether or not people will be creative.

01:21:38.520 | And I think the short takeaway

01:21:40.120 | that makes the most sense in terms of framing this,

01:21:42.600 | and we cover this on the episode on bipolar disorder,

01:21:45.360 | sometimes called bipolar depression,

01:21:47.160 | is that in professions

01:21:48.720 | where there's a lot of creativity required

01:21:50.860 | in order to succeed,

01:21:51.880 | so again, musicians, composers, artists, et cetera,

01:21:55.220 | you tend to find more manic depression,

01:21:57.880 | and manic depression, at least in the manic states,

01:22:00.880 | the hyperactive states,

01:22:02.600 | are correlated with elevated levels of dopamine.

01:22:05.460 | Likewise, it has been seen over and over throughout history

01:22:10.680 | that individuals that have mild forms of schizophrenia

01:22:13.480 | or even full-blown schizophrenia,

01:22:15.640 | many famous painters, for instance, or musicians,

01:22:18.920 | they are known to have elevated levels of dopamine,

01:22:21.580 | and they are quite creative.

01:22:22.740 | Now, that doesn't mean everybody who's creative

01:22:24.500 | has elevated levels of dopamine,

01:22:26.280 | although it's likely that their levels of dopamine

01:22:28.500 | are at least not diminished,

01:22:29.620 | and it doesn't mean that non-creative people

01:22:31.440 | have low levels of dopamine,

01:22:32.560 | so don't get carried away with the interpretation here,

01:22:34.780 | but the point is this.

01:22:35.880 | Dopamine levels strongly relate to the probability

01:22:41.080 | that you can engage in convergent and divergent thinking,

01:22:43.960 | and they do so in the following way.

01:22:45.840 | When dopamine levels are high,

01:22:49.000 | divergent thinking is more likely.

01:22:51.140 | That is, when people have a lot of dopamine

01:22:53.260 | circulating in their system,

01:22:54.880 | they tend to be very expansive with their ideas.

01:22:57.460 | They tend to brainstorm a lot.

01:22:58.680 | They tend to be comfortable and even want to,

01:23:02.520 | or reflexively, throw out a lot of ideas

01:23:05.260 | that sometimes even seem a little disconnected.

01:23:07.860 | Some people might think of this as kind of

01:23:09.680 | attention deficit, but it's not.

01:23:11.520 | It's really the idea of throwing out disparate ideas, right?

01:23:16.040 | You know, you hear sometimes, you know,

01:23:17.440 | you throw things against the wall and see what sticks.

01:23:19.360 | Well, these people, that's obviously an analogy,

01:23:21.960 | but people are throwing lots of things against the wall

01:23:25.120 | and seeing what stick,

01:23:26.240 | and then seeing how the things that stick fit together.

01:23:28.480 | That's divergent thinking,

01:23:29.700 | and elevations in dopamine

01:23:31.600 | tend to increase divergent thinking.

01:23:34.020 | However, they tend to do this

01:23:36.160 | in kind of an inverted U-shape way.

01:23:38.680 | For those of you that are watching on YouTube,

01:23:39.860 | I'm just drawing kind of a hump, obviously,

01:23:42.320 | and for those of you listening,

01:23:43.620 | just imagine a U, the shape of a letter U,

01:23:46.860 | and then just flip it upside down so it looks like a bump.

01:23:49.680 | Turns out that when dopamine levels are very low,

01:23:51.660 | there's a low probability of divergent thinking.

01:23:53.820 | When dopamine levels are high, as I mentioned before,

01:23:56.080 | there's a high level or probability of divergent thinking.

01:23:59.140 | But when dopamine levels go very, very high,

01:24:02.480 | then there's, again, a reduction in divergent thinking.

01:24:05.480 | In other words, there's a kind of a sweet spot

01:24:07.840 | of elevated dopamine for divergent thinking.

01:24:10.320 | And again, divergent thinking is critical

01:24:13.140 | for the creativity process,

01:24:14.480 | because creativity by definition

01:24:16.600 | is taking a novel set of ideas

01:24:19.200 | and arranging them in a particular way,

01:24:21.200 | or taking existing ideas and arranging them in a novel way,

01:24:25.180 | that then you eventually converge on some new product,

01:24:28.120 | new idea, new song, et cetera.

01:24:29.720 | Now, convergent thinking follows a very different pattern.

01:24:33.960 | When dopamine levels are high,

01:24:36.480 | convergent thinking is not very likely.

01:24:39.560 | And when dopamine levels are low,

01:24:41.320 | convergent thinking is very likely.

01:24:43.060 | So here, using arguably a very reductionist view,

01:24:47.040 | we're looking at all of this thing of,

01:24:48.560 | we're calling creativity

01:24:49.400 | through a very neurosciency reductionist lens,

01:24:51.680 | we can say this.

01:24:52.600 | The creative process involves going into a state

01:24:55.500 | where you're willing to consider a lot of options,

01:24:58.160 | many of which seem distantly

01:24:59.940 | or not even connected to one another.

01:25:01.660 | And dopamine facilitates that divergent thinking state

01:25:04.940 | in which you are perfectly happy

01:25:06.440 | and in fact experience a kind of a joy or elation,

01:25:10.960 | a comfort and a pleasure

01:25:13.560 | in organizing all these different ideas

01:25:15.420 | that to anyone else might seem not that related.

01:25:19.140 | But when your dopamine levels are elevated,

01:25:21.200 | these all seem like great ideas

01:25:22.440 | and that maybe there are connections there, right?

01:25:24.360 | You're not accepting all of them as true and valid

01:25:26.400 | and interesting and combining them.

01:25:28.300 | But there's this idea that,

01:25:30.780 | it's worth entertaining the possibility,

01:25:32.640 | at least for moments.

01:25:34.400 | And then as dopamine levels drop,

01:25:38.020 | there is the process of convergent thinking,

01:25:39.800 | which is taking options down off the wall,

01:25:42.800 | saying, no, no, that doesn't fit with that,

01:25:45.320 | doesn't fit with that, but ah, that fits with that.

01:25:47.680 | And that can work, that feels right or sounds right

01:25:50.760 | or looks right.

01:25:52.240 | That's the creativity process.

01:25:54.020 | And so I think this is not just important

01:25:56.820 | for understanding cannabis,

01:25:58.280 | which we'll get back to in a moment,

01:25:59.720 | but it's important for understanding creativity

01:26:02.080 | and brain states in general.

01:26:03.820 | Brain states are not, as we would say,

01:26:05.700 | a square wave function.

01:26:06.600 | You don't just drop into a trench of creativity.

01:26:08.640 | Creativity is not an event, it's a process.

01:26:11.680 | And what I'm telling you is that it's a process

01:26:14.120 | that involves divergent thinking and consideration,

01:26:16.080 | a lot of different ideas.

01:26:17.080 | That's correlated with high, but not too high dopamine.

01:26:20.920 | And then one has to transition into a state

01:26:24.640 | of convergent thinking,

01:26:25.800 | which is really homing in on the ideas

01:26:28.300 | that seem to have validity or that could have validity

01:26:31.020 | and getting rid of everything else.

01:26:32.380 | And that's associated with low dopamine.

01:26:34.480 | It's more about logical implementation and consideration

01:26:37.680 | as opposed to thinking about and considering everything.

01:26:40.880 | So let's now return to the question of whether or not

01:26:42.960 | cannabis and its different components increase creativity.

01:26:46.960 | And when you look at the literature on this,

01:26:50.240 | you find studies that very clearly point to a yes,

01:26:53.840 | it increases creativity.

01:26:55.640 | And it's not surprising, therefore,

01:26:57.480 | that cannabis can increase dopamine transmission,

01:27:00.960 | that is dopamine levels, in certain brain areas,

01:27:03.360 | in particular brain areas involved in thinking and planning.

01:27:06.720 | Okay, so cannabis increases dopamine in these areas,

01:27:09.400 | elevated dopamine increases divergent thinking,

01:27:11.960 | and divergent thinking is associated with creativity.

01:27:14.280 | And there are studies that support the idea

01:27:16.360 | that cannabis can increase creativity.

01:27:20.220 | However, there are at least as many studies

01:27:23.700 | that say that cannabis does not increase creativity,

01:27:26.720 | that cannabis increases consideration of multiple ideas,

01:27:30.060 | perhaps through elevation of dopamine and related systems,

01:27:33.820 | but that ultimately the ideas that converge from that

01:27:36.840 | are not truly creative ideas.

01:27:38.340 | At least they don't make the criteria

01:27:39.680 | for creative brainstorming and extraction of ideas

01:27:42.880 | that are truly novel, so it doesn't increase creativity.

01:27:46.480 | So which one is it?

01:27:48.040 | Well, fortunately, there's an entirely distinct set

01:27:50.920 | of literature that has taken all the other literature

01:27:53.420 | into consideration, and here's where we arrive.

01:27:56.320 | So there's a really nice study that explored creativity

01:27:59.120 | in cannabis users, and we will provide a link to this study.

01:28:02.760 | First author is Emily LaFrance, and the title of the paper,

01:28:06.600 | it's somewhat amusing in its own right,

01:28:08.740 | which is, it starts with a question.

01:28:10.760 | Inspired by Mary Jane, of course,

01:28:12.540 | Mary Jane being one of the kind of old school versions

01:28:14.980 | of ways of talking about cannabis or marijuana.

01:28:18.380 | Nowadays, people refer to it mainly as pot,

01:28:20.620 | has other names too, of course.

01:28:22.400 | And the title of the paper is Inspired by Mary Jane,

01:28:24.880 | Mechanisms Underlying Enhanced Creativity in Cannabis Users.

01:28:28.200 | And I really like this study for a couple of reasons.

01:28:30.820 | First of all, they looked at people who did not use cannabis

01:28:35.820 | as well as people who use cannabis.

01:28:38.660 | So they had two different groups,

01:28:39.920 | but they did not evaluate creativity of the cannabis users

01:28:44.760 | while they were under the influence of cannabis.

01:28:47.200 | They looked at the level of creativity

01:28:50.520 | in these cannabis users

01:28:52.560 | when they were not under the influence of cannabis

01:28:55.380 | and asked whether or not their ability to be creative

01:28:58.280 | was enhanced by cannabis.

01:28:59.680 | Now we're going to compare this to studies

01:29:01.840 | in which people come into the laboratory

01:29:03.880 | and actually use cannabis,

01:29:05.040 | and then they evaluate creativity under that context.

01:29:08.560 | But this study has some unique takeaways

01:29:10.660 | that I think are really interesting.

01:29:11.880 | First of all, they did, yes,

01:29:14.400 | see evidence for enhanced creativity.

01:29:16.880 | And when I say enhanced creativity,

01:29:18.360 | I mean within the context of this divergent thinking thing

01:29:21.740 | that I talked about a moment ago.

01:29:23.340 | And when I say enhanced,

01:29:25.580 | I mean significantly greater than in non-users,

01:29:28.020 | so people that don't use cannabis.

01:29:29.940 | So right now I can imagine that all the cannabis users

01:29:32.120 | are cheering, yes, cannabis increases creativity,

01:29:35.160 | makes people more creative than they would be otherwise.

01:29:37.760 | Well, this is interesting.

01:29:39.420 | We have to ask ourselves how that was accomplished.

01:29:42.960 | And it turns out that one of the major ways

01:29:44.640 | in which it was accomplished is that cannabis users,

01:29:47.600 | even if they are not under the influence of cannabis,

01:29:51.040 | are far more open to novel ideas,

01:29:54.680 | and they have a more explorative and sort of reduced anxiety

01:29:58.960 | or I should say lower anxiety mode of thinking

01:30:01.440 | when they explore novel ideas,

01:30:02.840 | which is essential for divergent thinking.

01:30:04.800 | So they observe both enhanced divergent and convergent

01:30:08.860 | creative type thinking in cannabis users.

01:30:12.920 | And the source of that, they conclude,

01:30:16.440 | is, and here I'll just quote,

01:30:18.500 | "Cannabis users' higher levels of openness to experience

01:30:21.280 | are responsible for their enhanced self-reported creativity

01:30:23.740 | and convergent thinking test performance."

01:30:26.040 | So it's not necessarily that cannabis is increasing

01:30:29.800 | the capacity of the brain areas

01:30:32.100 | that are associated with creativity,

01:30:33.920 | but rather cannabis appears to be increasing in openness

01:30:38.920 | and probably doing that in part through lowering anxiety

01:30:42.480 | in particular people.

01:30:43.580 | And that openness is leading to inclusion of more ideas

01:30:48.600 | during the divergent thinking process, right?

01:30:51.160 | They're willing to consider throwing up more things

01:30:53.300 | on the wall to see if they stick, so to speak.

01:30:55.920 | So in their conclusions, they have a really nice statement.

01:30:58.320 | Again, I'll just read from the paper

01:31:00.160 | because they said it better than I ever could.

01:31:02.320 | Quote, "While mainstream media has propagated the idea

01:31:05.000 | that cannabis expands the mind and enhances creativity,

01:31:08.440 | our results show the link between cannabis and creativity

01:31:10.960 | is largely a spurious correlation."

01:31:13.640 | Meaning that it's not the case

01:31:16.040 | that cannabis increases creativity.

01:31:19.260 | But, and I inserted the but in this quote,

01:31:23.660 | "But driven by differences in personality

01:31:28.560 | that are related to cannabis use.

01:31:30.600 | For example, openness to experience

01:31:32.520 | that are related to both cannabis use

01:31:34.240 | and augmented creativity."

01:31:36.780 | This is a real chicken egg argument.

01:31:38.680 | What do I mean by that?

01:31:39.840 | What I mean is this paper finds

01:31:42.560 | that people who are more open to experience

01:31:46.040 | are more likely to use cannabis

01:31:48.320 | and people who use cannabis

01:31:49.920 | are going to be more open to new experiences.

01:31:53.440 | And that combination of features, openness to experience

01:31:56.840 | and what that openness to new experiences brings

01:32:00.440 | enhances the convergent and divergent thinking

01:32:03.680 | that is characteristic of the creative process.

01:32:06.760 | So in short, cannabis increases creativity

01:32:10.040 | but through changes in personality

01:32:12.420 | that tap into the creative process

01:32:14.720 | rather than directly impacting the neural circuits

01:32:18.300 | that for instance, turn on creativity.

01:32:21.080 | And I have to say this study is really important

01:32:24.080 | because by exploring cannabis users

01:32:28.360 | not while under the influence of cannabis,

01:32:30.880 | they were able to tap into this very important

01:32:33.960 | what I believe to be fact.

01:32:36.060 | Because if you think about a study

01:32:37.520 | in which you would have one group using cannabis

01:32:40.440 | and another group not using cannabis

01:32:42.080 | and then you give them some tasks that taps into creativity,

01:32:44.880 | you will see effects and very likely you'll see effects

01:32:47.360 | where cannabis might even increase divergent convergent

01:32:49.680 | thinking and creativity.

01:32:51.040 | Those results have actually been published

01:32:52.320 | many times before.

01:32:53.800 | But given the varied effects of cannabis and THC

01:32:56.640 | that we talked about earlier

01:32:57.520 | through all that complex signaling stuff,

01:32:59.620 | you can imagine that there will also be other studies

01:33:01.920 | and in fact there are where divergent and convergent thinking

01:33:06.040 | and creativity is not assisted by cannabis

01:33:09.200 | and might even be reduced by ingesting cannabis.

01:33:11.940 | However, if one considers that divergent thinking

01:33:14.800 | is absolutely crucial to the creativity process

01:33:18.640 | and the range of things that one will explore

01:33:21.660 | will be enhanced by openness

01:33:24.280 | and by reduced levels of anxiety.

01:33:26.820 | So a willingness to explore different options,

01:33:28.760 | some of which might seem completely crazy

01:33:31.180 | and cannabis increases the personality types

01:33:34.260 | and reduces the anxiety that create that sense of openness.

01:33:38.080 | Well, then it makes perfect sense

01:33:39.340 | why cannabis would increase creativity

01:33:42.600 | in certain individuals, but not directly.

01:33:45.280 | And this study, the one I just referred to,

01:33:47.940 | which I should say was published

01:33:49.180 | in the journal "Consciousness and Cognition"

01:33:50.920 | and again, we'll provide a link to it,

01:33:53.040 | did a wonderful job of teasing out this impact of cannabis

01:33:57.800 | on personality, which then impacts creativity.

01:34:01.280 | So if somebody asks you or if you're wondering

01:34:03.420 | or if you feel like cannabis increases creativity,

01:34:06.560 | in some sense, the answer is yes,

01:34:08.080 | but the answer is yes because of the ways

01:34:10.260 | that it shapes openness to new ideas

01:34:13.120 | and can, I should say can because not in everybody,

01:34:15.980 | but can in some individuals reduce anxiety.

01:34:19.180 | What this means is that if you are somebody

01:34:21.960 | who experiences anxiety or increased levels of focus

01:34:26.960 | from cannabis, regardless of the strain,

01:34:30.880 | and here I have to imagine people

01:34:31.960 | are exploring different strains

01:34:33.300 | if they're exploring them at all,

01:34:35.500 | exploring different modes of delivery,

01:34:36.840 | smoking or ingestible, et cetera.

01:34:38.700 | If you're somebody who experiences anxiety,

01:34:41.640 | it's very likely that you won't have the increased openness

01:34:46.160 | to experience and divergent ideas

01:34:49.420 | that will facilitate creativity.

01:34:50.840 | However, if you are somebody

01:34:52.040 | who achieves heightened levels of relaxation

01:34:54.700 | and reduced levels of anxiety from cannabis,

01:34:57.580 | regardless of which strain we happen to be talking about,

01:35:00.400 | well, then yes, it will position you

01:35:03.060 | to be in a heightened state of creativity,

01:35:05.720 | at least as defined by convergent and divergent thinking.

01:35:08.520 | One of the more characteristic,

01:35:10.160 | or I should say stereotype qualities

01:35:13.320 | of people that smoke a lot of marijuana

01:35:15.380 | or ingest cannabis through other means

01:35:18.100 | is their changed patterns of speech.

01:35:20.320 | In fact, there's a kind of a lore in the clinical realm

01:35:25.320 | that you can predict or get some strong indication

01:35:29.400 | as to whether or not somebody is a cannabis user

01:35:31.720 | or a pot smoker based on their voice

01:35:34.040 | and their particular tone of voice

01:35:37.200 | and their lack of inflection.

01:35:39.240 | There's a lot of speculation here,

01:35:40.680 | but fortunately it's been studied.

01:35:42.360 | So I'd like to discuss now

01:35:43.640 | whether or not cannabis can impact patterns of speech,

01:35:46.720 | both acutely, meaning while under the influence of cannabis

01:35:50.080 | and over time in chronic cannabis users.

01:35:53.640 | And when I say chronic cannabis use,

01:35:55.160 | I want to be very specific what I mean.

01:35:56.800 | Chronic cannabis use does not necessarily mean

01:35:59.000 | that people are smoking cannabis

01:36:00.240 | or ingesting cannabis every day.

01:36:02.080 | Although certainly if they are,

01:36:03.040 | that qualifies as chronic use.

01:36:05.360 | Chronic use is regular use over time

01:36:07.760 | of anywhere from twice a week or more.

01:36:10.200 | So using cannabis once a month

01:36:11.820 | would not be considered chronic use,

01:36:13.320 | even if it's for many, many years.

01:36:15.520 | Using cannabis or ingesting cannabis in some way or form

01:36:18.640 | twice a week would be considered chronic use.

01:36:21.400 | And then of course,

01:36:22.240 | some of you out there are going to ask me to split hairs

01:36:24.040 | and say, well, what if somebody uses it twice a month?

01:36:26.560 | Well, listen, the clinical literature

01:36:28.860 | and the scientific literature don't get that specific.

01:36:31.460 | And of course there are an infinite number of ways

01:36:33.320 | to arrange one's cannabis use,

01:36:35.600 | everything from zero, none at all,

01:36:37.440 | to constantly every day, all day and everywhere in between.

01:36:41.160 | But think of chronic use as twice a week or more.

01:36:44.960 | Think of occasional use as less than that

01:36:47.600 | and realize that within the realm of chronic use, excuse me,

01:36:51.320 | that or more can be anywhere from twice a week

01:36:54.360 | to every day to just in the evenings, et cetera.

01:36:57.080 | The effects of chronic use of cannabis,

01:37:01.480 | as I just defined it, on speech have been studied

01:37:06.800 | because of this characteristic drawing out

01:37:11.560 | of certain syllables, a slowing of speech,

01:37:14.660 | and in many cases, a total change or alteration

01:37:19.100 | in the way that people speak and use language,

01:37:23.140 | both when under the influence of cannabis

01:37:25.620 | and when not under the influence of cannabis

01:37:28.020 | if they are chronic users.

01:37:29.840 | And here, we really want to distinguish between THC and CBD

01:37:33.900 | and just make it really simple and say that CBD

01:37:37.620 | is not responsible for most of the psychoactive effects

01:37:41.260 | of cannabis, whereas THC is.

01:37:43.780 | And again, the ratio of CBD to THC

01:37:45.480 | is going to be relevant there,

01:37:47.160 | but let's just think about cannabis and THC

01:37:50.000 | as one in the same for this portion of the discussion,

01:37:52.840 | realizing that, of course,

01:37:53.680 | they are not exactly the same thing.

01:37:55.640 | There's an excellent study entitled

01:37:57.220 | "Adults with History of Recreational Cannabis Use

01:37:59.680 | Have Altered Speech Production."

01:38:01.840 | And we will provide a link to that.

01:38:02.840 | First author, Adam Vogel, really liked this paper.

01:38:06.040 | It was published in the journal "Drug and Alcohol Dependence."

01:38:09.540 | We will provide a link to it for you

01:38:11.860 | if you'd like to peruse it in more detail.

01:38:14.320 | The title itself,

01:38:15.640 | "Adults with a History of Recreational Cannabis Use

01:38:17.920 | Have Altered Speech Production,"

01:38:20.040 | tells you pretty much everything you need to know,

01:38:22.260 | except there's some important nuance in here

01:38:24.700 | because, as I mentioned earlier,

01:38:26.820 | people who smoke sativa varieties of cannabis

01:38:30.140 | oftentimes will become more talkative, much more talkative.

01:38:34.400 | However, whether or not people tend to rely

01:38:37.300 | on sativa cannabis use or indica cannabis use,

01:38:42.300 | there is a very consistent finding

01:38:44.920 | that people who are chronic users,

01:38:46.280 | again, twice a week or more,

01:38:48.040 | recreational use or medicinal use,

01:38:50.700 | undergo pretty profound changes in the way that they speak,

01:38:54.320 | but in a very specific set of ways.

01:38:57.880 | Now, first of all,

01:38:59.720 | the changes in speech shouldn't surprise us at all

01:39:02.600 | because both sativa varieties of cannabis

01:39:05.700 | and indica varieties of cannabis

01:39:08.100 | impact those brain centers involved in movement,

01:39:10.800 | the basal ganglia.

01:39:11.980 | Remember the go/no-go circuitry,

01:39:13.660 | the circuitry that makes you want to do things

01:39:15.480 | and the circuitry that makes you want to withhold action,

01:39:18.080 | and it tends to shift the body and brain

01:39:21.040 | toward more inaction.

01:39:22.680 | And cannabis impacts CB1 receptors in the cerebellum,

01:39:27.180 | which is involved in motor planning, execution, and balance.

01:39:31.120 | So regardless of whether or not people are using cannabis

01:39:35.000 | of the sativa or the indica variety,

01:39:37.520 | there are disruptions in motor circuitry.

01:39:39.460 | And as you may have heard,

01:39:40.900 | if you listen to our episode with Rockefeller professor,

01:39:44.480 | Dr. Eric Jarvis, who works on speech and movement,

01:39:48.040 | speech is movement, right?

01:39:50.640 | The movements of the mouth, the movements of the hands,

01:39:53.160 | those are intimately related in terms of our speech.

01:39:55.840 | In fact, the centers of the brain involved in hand movements

01:39:58.920 | are part of the speech areas and vice versa.

01:40:01.440 | Eric actually pointed out that if you put your hands

01:40:04.180 | behind your back,

01:40:05.040 | provided you normally do have use of your hands,

01:40:07.280 | it actually will reduce your fluidity of speech.

01:40:10.280 | And so I'm going to put them back in front of me now.

01:40:12.480 | The point is smoking marijuana or consuming marijuana

01:40:18.280 | by edible changes one's speech

01:40:21.520 | and does in a very specific way.

01:40:23.040 | And in this study by Adam Vogel and colleagues,

01:40:26.660 | they explored a huge different variety of aspects of speech.

01:40:30.460 | And this can be done using spectral processing,

01:40:32.640 | which is, you know, fancy nerd speak

01:40:34.180 | for looking at how much inflection there is

01:40:36.440 | or looking at how long people hold vowels

01:40:38.720 | or consonants, et cetera.

01:40:39.860 | And again, these are people

01:40:40.820 | not under the influence of cannabis,

01:40:42.800 | but rather people who tend to be under the influence

01:40:45.680 | of cannabis when not participating in the study.

01:40:48.200 | In other words, chronic recreational cannabis users.

01:40:51.360 | So what are the two major shifts that cannabis causes

01:40:54.680 | on our patterns of speech?

01:40:56.080 | Well, the first one is a change

01:40:57.920 | in what's called spectral tilt.

01:40:59.900 | And that's fancy nerd speak for vocal effort and intensity.

01:41:03.740 | So I'm not a pot smoker, I confess,

01:41:06.720 | but if I were to say the sentence,

01:41:10.840 | vocal effort and intensity

01:41:13.420 | are important components of speech.

01:41:16.180 | That's the way I would say that sentence

01:41:17.940 | if I was striving to enunciate very carefully

01:41:20.500 | and to accent certain words and syllables.

01:41:24.180 | A pot smoker or somebody who uses recreational cannabis

01:41:28.460 | fairly often would have reduced spectral tilt,

01:41:32.500 | AKA vocal effort and intensity,

01:41:34.940 | and might say spectral tilt is vocal effort and intensity,

01:41:39.220 | and it differed between groups

01:41:40.440 | and appeared to change in line

01:41:41.660 | with the duration of abstinence from cannabis use.

01:41:44.860 | That I think is not a far cry

01:41:47.080 | from the change in spectral tilt that they observed here.

01:41:49.520 | In addition, there are changes in verbal timing,

01:41:54.080 | that is pronunciation of words

01:41:56.620 | and accenting particular syllables of words

01:42:00.220 | in people that consume cannabis or smoke cannabis.

01:42:04.700 | So rather than emphasize particular words within a sentence,

01:42:09.300 | so again, I'll just use a sentence from the paper

01:42:11.260 | so that you can gain more knowledge from the paper.

01:42:13.500 | Cannabis, and I'll say it the way that I would say it

01:42:16.020 | since I'm not a cannabis user.

01:42:18.960 | Cannabis, marijuana,

01:42:20.260 | is the most commonly used illicit drug in the world

01:42:22.540 | with approximately 4% of adults age 15 to 64 years

01:42:26.380 | reporting recent use.

01:42:27.660 | And the citation is from the United Nations Office

01:42:30.100 | on Drugs and Crime 2019.

01:42:33.020 | So that would be the way

01:42:34.020 | that I would typically read that sentence.

01:42:35.900 | And having gone into the data on this paper

01:42:38.420 | and of course evaluated references therein

01:42:41.140 | and listened to some of the spectral analysis

01:42:44.180 | that they include as data,

01:42:46.180 | you can literally go into these papers online

01:42:47.940 | and hear recordings of people who are cannabis users

01:42:51.220 | or non-cannabis users.

01:42:52.780 | And I'll try and give you a clear sense

01:42:55.300 | without picking an extreme example

01:42:57.720 | of how somebody who's a fairly consistent

01:43:00.720 | or even occasional cannabis user

01:43:02.520 | might read that very same sentence.

01:43:04.260 | Cannabis, marijuana,

01:43:07.700 | is the most commonly used illicit drug in the world

01:43:10.380 | with approximately 4% of adults age 15 to 64 years

01:43:14.420 | reporting recent use.

01:43:15.860 | And the citation comes from the United Nation Office

01:43:18.340 | on Drugs and Crime 2019.

01:43:20.960 | Now you'll notice that wasn't a dramatic difference.

01:43:23.440 | And of course I could have taken the liberty

01:43:25.440 | to pick an extreme example

01:43:26.760 | of the sort that they did occasionally observe

01:43:29.480 | in evaluating subjects for this paper.

01:43:31.700 | I could have said something like cannabis,

01:43:34.060 | marijuana is the most commonly used illicit drug,

01:43:36.400 | but frankly that would have been

01:43:37.640 | selecting an outlier example.

01:43:39.340 | And I don't want to do that.

01:43:40.200 | I don't want to skew the data as they say.

01:43:42.680 | Rather, if you heard the first time I read the sentence

01:43:47.040 | and the second time I read the sentence,

01:43:48.280 | what's mainly different is the difference

01:43:51.880 | in the amount of annunciation

01:43:54.200 | and accenting of particular words

01:43:56.080 | and symbols within a sentence.

01:43:57.480 | So the total content that's delivered is exactly the same.

01:44:00.360 | And while I wasn't measuring my pace,

01:44:02.560 | the overall rate of communication is essentially the same,

01:44:07.360 | but there's less sort of lilting

01:44:09.400 | and falling of the voice and less accenting.

01:44:11.240 | That's the major consistent effect of cannabis use.

01:44:14.320 | Now, of course, there are examples of people

01:44:16.320 | who are using a lot of cannabis

01:44:18.640 | and it impacts brain centers involved in movement and speech.

01:44:21.720 | So much so that they really do have

01:44:23.840 | the really drawn out kind of nah.

01:44:26.560 | And oftentimes this will be detected in the laugh.

01:44:29.080 | You know, there's this sort of stereotypical stoner laugh

01:44:31.840 | as it's sometimes called,

01:44:32.980 | rather than say ha ha ha or that's a fake laugh, obviously.

01:44:36.720 | It's hard to make myself laugh

01:44:37.860 | if something's not actually funny.

01:44:38.920 | I'll have to think of something funny.

01:44:40.360 | When people will say ha,

01:44:41.480 | like that's a bit more of the way I might laugh,

01:44:43.340 | like ha, sort of the inspiratory laugh or the ha,

01:44:46.820 | which is expiratory laugh.

01:44:48.480 | People who use cannabis chronically

01:44:50.200 | will often do the ah, right?

01:44:52.180 | Which is sort of the back of the throat, ah.

01:44:54.560 | It's sort of this,

01:44:56.280 | it's neither inspiratory nor expiratory laugh.

01:44:58.400 | And believe it or not,

01:44:59.220 | there's an entire literature on inspiratory inhaling

01:45:01.440 | versus expiratory laughs.

01:45:03.000 | And there's also a literature on cannabis

01:45:06.720 | altering the pattern of inspiratory and expiratory laughs.

01:45:09.400 | It almost sounds like a sarcastic laugh

01:45:11.780 | when in fact they may not be feeling sarcastic at all.

01:45:14.320 | And I have a very close friend and colleague

01:45:16.880 | who's a phenomenal neurosurgeon and neuroscientist

01:45:19.240 | by the name of Dr. Eddie Chang.

01:45:20.480 | He's the chair of neurosurgery at UCSF and his lab.

01:45:23.800 | And him are expert in the study

01:45:25.820 | of neuroscience controlling language and speech.

01:45:29.560 | And he often tells me that he can predict

01:45:34.100 | with almost certainty whether or not somebody

01:45:36.240 | is a regular cannabis user

01:45:38.220 | based not just on the patterns of speech that they use,

01:45:42.280 | but even just by recording specific neurons in their brain

01:45:45.300 | that underlie the laugh reflex

01:45:47.840 | and certain patterns of speech.

01:45:49.440 | So this idea that cannabis use changes your ability

01:45:52.540 | to speak and enunciate clearly does appear to be true.

01:45:55.820 | And the stereotype that cannabis use

01:45:58.560 | tends to create more of a drawl

01:46:00.640 | or kind of a, if you will, a laziness in the laugh

01:46:04.800 | and some of the reflexive enunciations that people use

01:46:08.000 | does also appear to be true.

01:46:09.260 | And I say all that of course with the caveat

01:46:11.940 | that many people out there will know individuals

01:46:15.020 | or perhaps you yourselves are individuals

01:46:17.960 | that may use cannabis, but that have incredible articulation

01:46:22.180 | probably better than mine

01:46:23.300 | and better than other people out there

01:46:24.660 | who speak for a living.

01:46:25.940 | So I'm not saying that 100% of people

01:46:28.020 | that use cannabis regularly can't speak well or clearly.

01:46:31.300 | That's simply not what I'm saying.

01:46:32.980 | And I don't want to communicate that idea at all.

01:46:35.520 | But it is the case that people who are regular cannabis users

01:46:38.740 | are impacting the neural circuits involved in movement.

01:46:41.300 | Movement also controls speech

01:46:43.100 | and therefore cannabis is impacting speech.

01:46:46.380 | Now I'd like to turn our attention to

01:46:47.780 | whether or not cannabis can increase sexual activity,

01:46:51.100 | sexual desire and or sexual function.

01:46:54.460 | So we're going to be talking about libido,

01:46:56.400 | about sexual desire and about effects of cannabis

01:46:59.300 | on hormones.

01:47:00.600 | And while this might sound like a discussion

01:47:02.660 | that's purely oriented towards recreational use of cannabis,

01:47:06.080 | that is people using cannabis to heighten

01:47:08.380 | or increase their sense of arousal for sexual activity,

01:47:12.020 | it actually ventures into the clinical realm too,

01:47:14.540 | meaning there have been excellent peer reviewed studies

01:47:17.600 | that I'll describe to you in a moment

01:47:19.100 | exploring the use of cannabis or THC more specifically

01:47:23.060 | for something called hypoactive sexual desire disorder,

01:47:26.980 | which refers to a persistent or recurrent deficiency

01:47:30.420 | or absence of sexual fantasies and thoughts

01:47:32.740 | and or desire for or receptivity to sexual activity.

01:47:37.300 | This is a disorder that is fairly common,

01:47:39.620 | anywhere from six to 9% of people,

01:47:41.900 | both males and females.

01:47:43.580 | It used to be considered higher prevalence in females

01:47:47.580 | than in males,

01:47:48.420 | but now those numbers seem to be evening out.

01:47:50.760 | So basically there are anywhere from six to 9%

01:47:54.440 | of people out there who have very diminished sexual desire.

01:47:58.680 | And so a number of those people are interested

01:48:01.260 | in figuring out ways to increase

01:48:02.620 | their amount of sexual desire.

01:48:04.260 | And of course there are people in the general population

01:48:07.180 | who may not have hypoactive sexual desire disorder,

01:48:10.660 | who are interested in using cannabis recreationally

01:48:13.340 | in order to increase their desire for

01:48:15.580 | or their experience of sexual activity.

01:48:18.540 | Now, first we have to acknowledge

01:48:19.860 | that sexual desire and activity

01:48:21.780 | is a complex set of processes,

01:48:24.060 | meaning it's not just one event, sex, the verb,

01:48:27.680 | it involves arousal, it involves sex, the verb,

01:48:31.740 | and it involves a whole set of mindsets and emotional states

01:48:35.340 | that vary tremendously between individuals.

01:48:37.780 | But once again, we can distill out a few basic principles

01:48:41.980 | and I should emphasize these are by no means

01:48:44.380 | the only chemicals in neural circuits

01:48:46.000 | involved in the sexual arc, as we'll call it,

01:48:48.940 | desire, the act of sex, et cetera,

01:48:51.720 | but they are central to it, they are vital to it.

01:48:54.260 | They would be considered what I would call necessary

01:48:56.980 | but not sufficient, okay?

01:48:58.380 | So there'll be other chemicals involved too,

01:49:00.260 | but the main chemicals in neural circuits

01:49:01.760 | are those involved in dopamine.

01:49:03.540 | So the so-called mesolimbic reward pathway

01:49:05.820 | in particular brain structure called nucleus accumbens,

01:49:08.740 | which we'll talk about more in a moment,

01:49:10.360 | is vital to all motivated behaviors

01:49:13.220 | and to the seeking out of all particular types

01:49:16.340 | of pleasurable experiences and sex is no exception.

01:49:18.960 | So when we hear that the nucleus accumbens is activated,

01:49:21.980 | that almost always means that dopamine has been released

01:49:24.820 | in that area and other areas of the brain and body,

01:49:27.540 | and we can consider dopamine central

01:49:29.500 | to the desire for, pursuit of, and act of sex.

01:49:34.860 | In addition to that, there are molecules like oxytocin,

01:49:38.500 | which are involved in pair bonding,

01:49:40.020 | and they're going to be neural circuits

01:49:41.140 | specific to the oxytocin circuitry,

01:49:43.580 | but in terms of sexual arousal and sexual behavior,

01:49:47.380 | it's really the dopamine pathway in this nucleus accumbens,

01:49:50.100 | which are especially vital.

01:49:51.840 | That allows us to address the question,

01:49:54.540 | does cannabis increase, decrease, or have no effect

01:49:59.540 | on sexual desire and/or the ability to have sex?

01:50:04.660 | And therein, we will find some very interesting answers

01:50:08.740 | because once again, it will point to the fact

01:50:12.180 | that the effects of cannabis on different individuals

01:50:15.940 | can be highly divergent,

01:50:18.020 | meaning in one set of individuals,

01:50:20.260 | cannabis will make them far less anxious,

01:50:22.780 | and in another set of individuals,

01:50:24.380 | the same strain of cannabis at the same dosage

01:50:26.740 | will make them extremely anxious.

01:50:28.320 | The same can be said also of sexual activity.

01:50:31.860 | And this was beautifully illustrated

01:50:33.980 | in the context of sexual desire

01:50:35.880 | in the journal "Psychopharmacology"

01:50:37.820 | in a paper published in 2017.

01:50:39.420 | The title of this paper

01:50:40.860 | is "Individual Prolactin Reactivity Modulates Response

01:50:44.500 | of Nucleus Accumbens to Erotic Stimuli

01:50:46.940 | During Acute Cannabis Intoxication, an fMRI Pilot Study."

01:50:51.420 | So I'll give a little bit of definition

01:50:53.580 | to some of the terms in the title

01:50:54.700 | that will make it easier for you to understand the paper,

01:50:57.620 | but then I'll just march through the results

01:50:59.100 | because they are very straightforward and easy to understand

01:51:01.820 | and very interesting.

01:51:03.380 | fMRI is just functional magnetic resonance imaging.

01:51:06.540 | So basically, subjects in this experiment

01:51:09.260 | came into the laboratory.

01:51:12.020 | They were either people who had not used cannabis before

01:51:16.180 | or who had used cannabis before.

01:51:19.180 | They were placed into a brain scanner,

01:51:20.940 | one of these fMRI devices.

01:51:22.660 | It looks like a tube that people are backed up into,

01:51:26.080 | and then they can view images in there,

01:51:27.460 | and their brain can be imaged

01:51:28.800 | without having to remove any skull

01:51:30.340 | or drill into the skull, no neurosurgery.

01:51:33.380 | The participants in this study

01:51:35.300 | were grouped according to whether or not

01:51:36.860 | they'd experienced any aphrodisiac effects

01:51:39.600 | during the intoxication with cannabis.

01:51:41.740 | So that would be the first group, group A.

01:51:43.740 | They literally called it group A for aphrodisiac.

01:51:45.940 | And then the second group,

01:51:47.060 | and this is the only thing I don't like about this study,

01:51:48.820 | is rather than call it group B,

01:51:50.300 | they called them group non-A,

01:51:52.660 | which just gets a little confusing.

01:51:54.700 | So I'll try and simplify all this.

01:51:56.420 | There are two groups,

01:51:57.820 | and one group experiences sexual arousal

01:52:02.180 | when under the influence of cannabis, THC specifically.

01:52:06.260 | The other group does not.

01:52:07.620 | And it turns out this is a very commonly observed

01:52:10.620 | divergence of effects of cannabis.

01:52:14.260 | Some people experience a lot of sexual arousal

01:52:16.800 | from cannabis and THC in particular,

01:52:19.180 | and some people do not.

01:52:20.560 | In fact, they experience suppression of sexual desire.

01:52:24.100 | And it's always been a little bit mysterious

01:52:25.940 | as to why that is.

01:52:27.940 | Well, in this study,

01:52:29.320 | they showed people in both groups erotic images,

01:52:33.720 | and they measured sexual arousal

01:52:35.880 | through a number of different measures.

01:52:36.940 | We won't go into all that.

01:52:37.840 | It was largely subjective.

01:52:39.300 | There've been other studies

01:52:40.240 | where they've actually measured things

01:52:42.040 | like erections in males and vaginal lubrication in females,

01:52:45.800 | the so-called autonomic responses

01:52:47.840 | that people can't lie about, so to speak,

01:52:51.240 | and that tap into other aspects

01:52:54.360 | of the so-called sexual arousal process.

01:52:57.640 | In this study, they also took blood samples

01:52:59.760 | to look at the concentration of things like cannabinoids.

01:53:03.160 | So this is a really nice study

01:53:04.440 | in that they actually measured how much THC

01:53:07.360 | was in the bloodstream in different individuals

01:53:09.660 | who reacted to these erotic stimuli in different ways.

01:53:12.400 | And they measured hormones,

01:53:14.080 | namely cortisol, which is a stress hormone,

01:53:16.280 | which tends to negatively correlate

01:53:17.800 | with sexual arousal and prolactin.

01:53:20.560 | And the interesting takeaway from the study

01:53:22.640 | was that for people,

01:53:24.960 | and it didn't matter if it was males or females,

01:53:27.440 | 'cause they looked at both,

01:53:28.800 | for people that experienced elevated prolactin levels

01:53:35.280 | under cannabis intoxication, that's how they referred to it.

01:53:39.240 | People take cannabis, they measured prolactin.

01:53:40.960 | Some people had elevated prolactin, some people did not.

01:53:43.900 | For the people that had elevated levels of prolactin,

01:53:48.000 | they did not observe activation of brain areas

01:53:52.440 | associated with sexual arousal,

01:53:54.340 | in this case, the right nucleus accumbens.

01:53:56.440 | So you have two nucleus accumbi, I guess they'd be called,

01:53:59.640 | one on each side of the brain,

01:54:00.800 | and the activation of that brain area

01:54:02.520 | is strongly associated with dopamine and with arousal,

01:54:05.520 | and sexual arousal in particular in this study.

01:54:07.880 | And if people had elevated prolactin,

01:54:10.000 | they did not experience activation of nucleus accumbens,

01:54:12.880 | and they did not report feeling sexually aroused

01:54:15.400 | to those pictures, at least not to the same degree

01:54:17.320 | as the other group.

01:54:18.520 | So some people's prolactin levels go up

01:54:20.620 | when they ingest cannabis,

01:54:22.680 | and those people do not achieve elevated levels

01:54:25.880 | of sexual arousal when under the influence of cannabis,

01:54:29.360 | even if they're looking at erotic stimuli.

01:54:32.200 | That makes sense because prolactin

01:54:35.740 | is mutually inhibitory, as we would say.

01:54:39.120 | It's kind of in a push-pull with dopamine.

01:54:41.040 | When dopamine levels are high,

01:54:42.280 | prolactin levels tend to be low,

01:54:44.560 | and when prolactin levels are high,

01:54:46.160 | dopamine levels tend to be low.

01:54:48.000 | The other group, so-called group A,

01:54:50.540 | that experienced elevated levels of sexual arousal

01:54:53.480 | when under the influence of cannabis and viewing erotic

01:54:56.140 | stimuli, that group did not show elevated levels

01:55:00.880 | of prolactin in response to cannabis.

01:55:03.800 | So this, I believe, resolves a longstanding controversy

01:55:07.480 | in the field, which is,

01:55:08.760 | does cannabis increase sexual arousal?

01:55:11.300 | Well, it depends.

01:55:12.280 | If you fall into the category of person

01:55:14.220 | who has elevated levels of prolactin in response to cannabis,

01:55:18.000 | then no, actually cannabis will suppress

01:55:20.940 | your sexual response and desire.

01:55:23.240 | If, however, you are in the category of person

01:55:26.400 | that does not have elevated levels of prolactin

01:55:29.840 | in response to cannabis,

01:55:31.700 | well then erotic stimuli can potentially,

01:55:35.080 | and in fact do, increase sexual arousal

01:55:37.760 | in the majority of individuals.

01:55:39.320 | Now, many of you are probably hearing this

01:55:40.820 | and wondering whether or not you fall into

01:55:43.400 | one category of individual or another.

01:55:45.860 | And the key thing here to understand is that

01:55:50.280 | levels of prolactin heading into the study

01:55:53.100 | did not predict, did not predict,

01:55:56.100 | whether or not people would respond to cannabis

01:55:59.140 | with elevated or non-elevated

01:56:02.300 | or even reduced levels of sexual arousal.

01:56:04.960 | It was whether or not people's prolactin levels went up

01:56:08.700 | or did not go up that predicted whether or not

01:56:11.700 | their levels of arousal would go up or not.

01:56:14.680 | So if you are somebody who, yes,

01:56:17.100 | does experience elevated levels of sexual arousal

01:56:20.440 | and function when under the influence of cannabis,

01:56:23.600 | well, that's very likely that cannabis

01:56:25.160 | does not increase your prolactin levels,

01:56:26.880 | at least not to a significant degree while you're taking it.

01:56:30.460 | And if you are somebody who does not experience increases

01:56:33.160 | in sexual arousal or function

01:56:35.000 | or even diminished sexual arousal and function

01:56:36.940 | when under the influence of cannabis,

01:56:38.340 | it's very likely the cannabis is increasing

01:56:40.400 | your levels of prolactin.

01:56:41.740 | Unfortunately, there's no way to know or predict

01:56:44.320 | based on some other measure.

01:56:46.360 | I think the outcome measure that is increased

01:56:49.080 | or not increased or even reduced sexual arousal

01:56:51.540 | is really the litmus test by which one can figure that out.

01:56:54.940 | While we are on the topic of the effects of cannabis

01:56:57.180 | on sexual function and hormones like prolactin,

01:57:00.340 | it's probably worth mentioning that cannabis

01:57:02.240 | has been studied extensively

01:57:04.100 | for its impact on other hormones.

01:57:06.260 | And we can summarize those literature in the following way.

01:57:09.940 | And here I'm referring to studies only on adults.

01:57:12.060 | We will talk about the developing brain and body

01:57:13.820 | in a little bit, but it is very clear

01:57:17.380 | that smoking cannabis increases prolactin levels.

01:57:22.380 | Very, very clear.

01:57:24.440 | Now you might say, didn't you just describe a study

01:57:27.840 | about a set of individuals whose prolactin didn't increase

01:57:31.480 | and as a consequence,

01:57:33.120 | their level of sexual desire went up?

01:57:35.760 | Yes, there are a subset of individuals

01:57:37.520 | for which that's true.

01:57:38.860 | But people who smoke cannabis

01:57:41.760 | do experience increases in prolactin.

01:57:45.380 | And that's especially pronounced in people

01:57:47.140 | that smoke cannabis more than twice a week.

01:57:49.780 | So this is important.

01:57:51.500 | Prolactin, as I referred to earlier,

01:57:54.420 | is reciprocal or mutually inhibitory with dopamine.

01:57:59.420 | One way to think about this is in the context

01:58:01.500 | of the normal sexual arousal arc,

01:58:03.600 | whereby dopamine is increased

01:58:05.380 | when people are sexually aroused.

01:58:07.220 | But then after orgasm, both in males and females,

01:58:10.640 | prolactin levels skyrocket.

01:58:12.800 | This is actually what creates

01:58:14.340 | the so-called refractory period for males

01:58:16.380 | during which they cannot achieve erection again

01:58:18.380 | for some period of time.

01:58:19.580 | That relates directly

01:58:21.660 | to how long the prolactin increase lasts, okay?

01:58:25.240 | Prolactin is also increased in new parents of all species,

01:58:30.220 | including humans, which at least partially explain

01:58:35.220 | some of the reported or typical reductions

01:58:38.480 | in sexual desire and activity in new parents.

01:58:41.040 | Now there are other reasons for that too, sleep deprivation,

01:58:43.140 | but nature is smart and has arranged a set of hormones

01:58:46.960 | and circuits in the brain and body

01:58:48.300 | such that when tending to a newborn

01:58:50.280 | is the most important thing, it relegates,

01:58:53.120 | it reduces the importance of producing more children

01:58:57.780 | and sexual activity in those moments

01:59:00.060 | and days and weeks, sometimes longer.

01:59:01.940 | So when prolactin levels are up, dopamine levels are down.

01:59:04.520 | Smoking marijuana more than twice a week

01:59:06.500 | significantly increases prolactin.

01:59:09.020 | There are fewer studies exploring

01:59:11.340 | whether or not edible marijuana has the same effect,

01:59:14.260 | although the preliminary evidence suggests that it does not.

01:59:18.180 | I get into this in a lot more detail in a future episode,

01:59:21.180 | all about hormones with Dr. Kyle Gillette,

01:59:24.100 | who's been on this podcast before, but he verified that,

01:59:27.100 | and my read of the literature is that the edible forms

01:59:31.260 | of marijuana, cannabis, probably, again,

01:59:35.260 | let's put an asterisk next to this,

01:59:37.060 | but it appears do not have as much

01:59:39.400 | of a prolactin elevating effect

01:59:41.060 | and therefore not as much of a dopamine suppressive effect

01:59:45.000 | and therefore not as much

01:59:46.140 | of a testosterone suppressing effect.

01:59:48.340 | And that gets to the issue of testosterone.

01:59:50.000 | Does cannabis marijuana suppress testosterone?

01:59:52.740 | And this is a very controversial literature and here's why.

01:59:55.620 | Some studies say, yes, it suppresses testosterone

01:59:59.700 | in males and females.

02:00:02.020 | And keep in mind that testosterone in females

02:00:03.700 | is vital for libido and cognitive function,

02:00:06.380 | cellular repair, et cetera.

02:00:08.380 | So it's not just important in males, of course.

02:00:11.340 | However, other studies say that cannabis

02:00:14.340 | does not decrease testosterone.

02:00:16.500 | And it seems to depend on whether or not the cannabis

02:00:20.460 | is brought into the system by way of smoking or edible.

02:00:23.620 | And it seems to depend on whether or not the cannabis

02:00:27.160 | is used chronically by an individual or acutely.

02:00:29.980 | And here, I just want to zoom out and say that studies

02:00:32.780 | on cannabis or drugs of any kind in humans

02:00:35.160 | are really complicated.

02:00:36.220 | If you think about it,

02:00:37.060 | someone has to come into the laboratory

02:00:38.740 | and let's say you want to study chronic cannabis use.

02:00:41.420 | Well, you can't keep them in the laboratory all the time.

02:00:43.940 | So you have to rely on their self-report

02:00:45.680 | of how often they use cannabis and in what form.

02:00:47.900 | And you can't really control from one individual

02:00:50.020 | to the next of how much cannabis and THC

02:00:51.940 | they're bringing into their system.

02:00:52.900 | One person might smoke cannabis out of a bong

02:00:55.620 | and take big, deep lungs full bong inhalations or such.

02:01:00.620 | Other people might smoke joints.

02:01:04.560 | Other people might use edibles.

02:01:06.100 | It becomes very complicated to know what people have done

02:01:08.420 | and that they're reporting it accurately.

02:01:10.300 | And no joke here,

02:01:11.440 | especially if marijuana is impacting

02:01:13.660 | the short-term memory systems.

02:01:14.940 | They might not actually remember.

02:01:16.140 | They might not be tracking it that well.

02:01:18.620 | Contrast that with studies of the acute use of cannabis

02:01:21.460 | and THC where people who are not regular users

02:01:24.040 | come into the laboratory and now suddenly

02:01:26.500 | with institutional guidelines and safety protocols

02:01:29.540 | are under the influence of THC and cannabis.

02:01:31.740 | Well, now you're dealing with a person

02:01:32.940 | who may not have experience with the elevated heart rate

02:01:37.120 | and blood pressure that's characteristic of cannabis

02:01:39.100 | 'cause it is a stimulant,

02:01:40.100 | at least when initially brought into the system,

02:01:42.060 | even if it might eventually lead to relaxation.

02:01:44.380 | So now you've got someone who's anxious

02:01:45.780 | or somebody who's not anxious, who's deeply relaxed,

02:01:48.780 | and you're trying to study these effects.

02:01:49.980 | So it's a moving target of sorts.

02:01:52.420 | It's very complicated to study marijuana and cannabis

02:01:56.060 | and its various derivatives in this way.

02:01:57.780 | Now you can probably appreciate better

02:01:59.860 | as to why there's so little nuanced data about sativa

02:02:03.540 | versus indica versus different ratios of CBD and THC.

02:02:07.980 | It's really difficult to do these studies

02:02:09.740 | in the first place.

02:02:10.620 | That said, the general rules are smoking marijuana

02:02:13.340 | increases prolactin in men and women,

02:02:14.900 | which will reduce dopamine and testosterone.

02:02:17.260 | Smoking marijuana chronically,

02:02:19.920 | meaning more than twice a week,

02:02:22.380 | does appear to reduce testosterone significantly

02:02:25.280 | and elevate so-called aromatase enzymes,

02:02:28.580 | which are the enzymes that convert testosterone

02:02:30.480 | into estrogen.

02:02:31.520 | This might partially explain the effect

02:02:33.740 | that occurs in about 35% of males,

02:02:36.540 | which is gynecomastia,

02:02:38.340 | which is a development of breast tissue in males,

02:02:41.060 | in particular young males

02:02:42.660 | who have elevated levels of testosterone

02:02:44.500 | or who are taking exogenous testosterone

02:02:47.320 | for testosterone replacement therapy,

02:02:49.300 | or if they're taking high doses, anabolic steroids,

02:02:51.740 | or in females that increase in breast size,

02:02:55.340 | which is due to additional estrogen

02:02:58.200 | from testosterone converted to estrogen.

02:02:59.900 | So it does appear that marijuana and cannabis

02:03:01.760 | increase estrogen, reduce testosterone,

02:03:03.720 | increase prolactin, especially in chronic users.

02:03:07.420 | Now, I'm sure that some people out there will say,

02:03:08.980 | well, their testosterone levels are exceedingly high

02:03:12.340 | or they are fine,

02:03:13.760 | meaning the constellation of symptoms

02:03:15.420 | associated with low testosterone and elevated estrogen

02:03:18.620 | are not present in them.

02:03:20.120 | That probably means one of two things or both.

02:03:25.080 | They either had elevated levels of testosterone

02:03:27.040 | to begin with, so their ceiling was higher,

02:03:28.700 | so bringing it down didn't have that much of effect,

02:03:30.640 | or that they have very low levels

02:03:33.460 | of aromatase in their system.

02:03:35.620 | There are some anecdotal evidence

02:03:38.160 | that smoking particular parts of the marijuana plant,

02:03:41.180 | in particular the seeds, can increase aromatase

02:03:45.380 | in the conversion of testosterone to estrogen.

02:03:47.380 | I think in the old days,

02:03:48.500 | the lore was the seeds make you sterile,

02:03:50.540 | and I think that was related to what I just told you,

02:03:52.660 | this increase in conversion of testosterone to estrogen.

02:03:55.780 | There's a vast literature

02:03:57.560 | on the effects of cannabis on fertility.

02:04:00.720 | It does seem, yes, it does seem to alter sperm motility

02:04:05.200 | and sperm health and function

02:04:06.600 | when taken chronically more than twice per week,

02:04:08.800 | in particular high doses of high potency THC.

02:04:12.100 | This is something we will cover in far more detail

02:04:14.280 | on a future episode all about fertility.

02:04:16.720 | And in females, there's an increase in estrogen

02:04:19.540 | as a consequence of smoking marijuana

02:04:22.440 | and increasing prolactin and estrogen in parallel.

02:04:26.400 | Whether or not that's detrimental isn't clear,

02:04:29.040 | although I point out that elevated estrogen and prolactin

02:04:33.760 | can be associated, again, can be associated,

02:04:36.160 | not necessarily, and certainly not causative,

02:04:38.640 | but can be associated with elevated levels of,

02:04:41.560 | or frequency of breast cancer detection.

02:04:43.580 | So cannabis and its effects on hormones

02:04:46.040 | are not without consequence.

02:04:47.600 | There are effects of cannabis on cortisol,

02:04:52.120 | in some individuals, it greatly increases cortisol

02:04:54.640 | due to the anxiety and paranoia it can create,

02:04:58.000 | and in other individuals, it reduces cortisol.

02:05:00.280 | Again, we have these divergent effects,

02:05:02.200 | but I want to be very clear.

02:05:03.720 | The effects on prolactin, meaning elevated prolactin,

02:05:05.920 | the effects on testosterone, meaning,

02:05:08.000 | at least most studies point to reduced levels of testosterone

02:05:10.800 | and increased estrogen, that seems to be true

02:05:13.880 | for most all individuals that chronically use cannabis.

02:05:17.720 | Whereas the effects on cortisol tend to be divergent,

02:05:21.380 | cannabis increases cortisol in some individuals

02:05:23.640 | and decreases cortisol in others.

02:05:25.240 | In general, increases in cortisol that are ongoing

02:05:28.640 | are not healthy for us, and so on.

02:05:31.940 | And then of course, there are other effects on hormones,

02:05:34.520 | and I'll just briefly summarize those,

02:05:35.920 | that THC in particular, not CBD, but THC in particular,

02:05:39.820 | is known to be strongly inhibitory

02:05:41.640 | for something called gonadotropin-releasing hormone.

02:05:43.940 | This is a hormone that's released from the brain,

02:05:45.960 | from the hypothalamus, that then feeds onto,

02:05:49.480 | or I should say, signals to the pituitary gland,

02:05:51.640 | which is also near the roof of your mouth,

02:05:52.980 | a lot of stuff happening near the roof of your mouth,

02:05:54.460 | it turns out, biologically,

02:05:56.060 | and reduced levels of gonadotropin-releasing hormone

02:05:59.200 | caused by cannabis use, reduced levels of LH,

02:06:01.940 | luteinizing hormone, and FSH,

02:06:03.620 | which reduce levels of testosterone

02:06:05.880 | and sperm production in males, and egg health,

02:06:10.580 | and ovulation, and menstrual function in females.

02:06:14.940 | Now, I'm sure there are a number of women out there

02:06:17.840 | who will say they have perfectly normal menstrual cycles

02:06:19.900 | despite using cannabis.

02:06:22.100 | I'm certainly not going to dispute that.

02:06:24.500 | But if you are somebody who's trying to maximize fertility,

02:06:28.140 | or regulate, or balance hormones,

02:06:30.820 | marijuana and cannabis reduces GnRH,

02:06:34.140 | that is the gonadotropin-release from the hypothalamus,

02:06:38.620 | and thereby reduces luteinizing hormone

02:06:40.700 | and follicle-stimulating hormone,

02:06:42.180 | which are released from the pituitary

02:06:43.820 | and travel in the bloodstream

02:06:45.460 | to support normal ovarian function and health,

02:06:48.560 | and normal testicular function and health

02:06:51.080 | in females and males, respectively.

02:06:53.200 | Up until now, I've been discussing the biological

02:06:55.300 | and psychological effects of cannabis.

02:06:57.920 | Now, I'd like to shift our attention

02:06:59.400 | to some of the negative health effects of cannabis,

02:07:02.500 | and shine light on some of the individuals

02:07:05.440 | or groups out there that need to be especially wary of,

02:07:08.860 | and probably avoid cannabis use entirely,

02:07:11.700 | including ingestion of cannabis by way of edible.

02:07:16.180 | And I frame things that way

02:07:17.300 | because I think there is an increasingly large number

02:07:20.060 | of people out there that appreciate

02:07:22.620 | that smoking tobacco or smoking cannabis,

02:07:27.320 | vaping tobacco, yes, vaping tobacco or vaping cannabis,

02:07:31.800 | each and all have negative health consequences

02:07:35.900 | on the lungs and on the so-called endothelial cells

02:07:38.860 | of the body, the cells that make up the vasculature,

02:07:41.200 | the capillaries and blood vessels.

02:07:43.360 | If you don't already know this,

02:07:45.120 | I'll make it very clear and I'll make it very brief.

02:07:48.600 | Whether or not you smoke or vape tobacco or cannabis,

02:07:53.440 | you are severely impairing the function

02:07:56.240 | of endothelial cells that make up the capillaries

02:07:58.860 | and blood vessels of your brain and body.

02:08:01.160 | And that is known to decrease cognitive capacity over time,

02:08:05.800 | increase probability of strokes,

02:08:07.600 | severely impact lung function,

02:08:11.000 | and also lead to things like peripheral neuropathies.

02:08:14.360 | It leads to sexual dysfunction

02:08:16.280 | because of lack of blood flow to the genitals,

02:08:19.680 | can lead to other aspects of reproductive damage,

02:08:22.480 | including to the ovaries and testes.

02:08:25.080 | Essentially, there is no other way to state it

02:08:27.200 | except that smoking and vaping

02:08:30.020 | have negative health consequences

02:08:32.480 | that are independent of the substances

02:08:35.620 | that people are trying to get into their bloodstream

02:08:38.980 | by smoking or vaping.

02:08:40.280 | So people smoke and vape tobacco

02:08:41.960 | and people smoke and vape cannabis.

02:08:44.160 | And in both cases,

02:08:45.640 | if we just set aside the direct effects of tobacco

02:08:49.000 | and the direct effects of cannabis,

02:08:52.420 | we can confidently say that the process of smoking,

02:08:56.060 | of inhaling smoke into the lungs,

02:08:57.760 | and yes, also vaping,

02:08:59.680 | bringing the chemicals that transport nicotine,

02:09:04.680 | or in this case, cannabis into the lungs by way of vaping,

02:09:08.120 | are both severely detrimental to endothelial cells.

02:09:11.500 | I think a few years ago when vaping wasn't as prominent,

02:09:14.380 | there was this question and this idea

02:09:16.360 | that maybe vaping was going to be far healthier

02:09:18.840 | or at least not as bad as smoking,

02:09:22.640 | but now we can see a huge number

02:09:24.880 | of negative health effects of vaping,

02:09:26.460 | some of which are distinct from the effects of smoking.

02:09:29.200 | So if you'd like more information on smoking versus vaping,

02:09:32.320 | please see the episode that I did on nicotine.

02:09:34.280 | We will also do an entire episode

02:09:36.080 | all about vaping in the future,

02:09:38.600 | but there's really no way to slice it and dice it

02:09:41.360 | or candy code it.

02:09:42.600 | The fact of the matter is that smoking has clear

02:09:45.560 | and severe negative health consequences,

02:09:48.080 | regardless of whether or not you're smoking tobacco

02:09:50.480 | or cannabis, THC,

02:09:52.820 | and vaping has negative health consequences,

02:09:57.780 | whether or not you're using the vape

02:09:59.400 | to bring in nicotine or THC

02:10:01.720 | or some combination of THC and CBD.

02:10:04.240 | That's simply the way it is.

02:10:05.560 | With that said, now I'd like to focus our attention

02:10:07.680 | on the direct effects that cannabis has,

02:10:10.480 | either by way of THC action or by way of CBD action

02:10:15.160 | in terms of positive or negative health effects

02:10:18.240 | on the brain and body.

02:10:19.200 | And we're going to explore that first as a function of age.

02:10:22.920 | And the reason we're going to do that is related to a fact

02:10:26.080 | that I mentioned at the beginning of the episode,

02:10:27.960 | which is that the CB1 and the CB2 receptors,

02:10:31.520 | the two receptors for cannabis to which THC and CBD and CBN

02:10:36.520 | and all other psychoactive compounds in cannabis bind to,

02:10:40.780 | to have their actions, are present throughout development.

02:10:45.320 | Believe it or not,

02:10:46.160 | they are present very soon after conception

02:10:49.340 | and the CB1 and CB2 receptors actually play a critical role

02:10:53.560 | in the development of the fetus.

02:10:55.760 | Now you might wonder why that is

02:10:58.400 | because of course the developing fetus

02:11:00.400 | doesn't necessarily expect to see cannabis

02:11:02.560 | or to be exposed to cannabis and THC and CBD.

02:11:05.840 | But as you recall, endogenous cannabinoids are present

02:11:10.600 | in the adult brain and body and endogenous cannabinoids,

02:11:14.320 | it turns out, are also present in the developing fetus.

02:11:16.920 | In fact, endogenous cannabinoids are present

02:11:19.560 | at much greater levels than the developing fetus

02:11:22.180 | than they are after a child is born.

02:11:25.840 | And levels of endogenous cannabinoids

02:11:27.800 | actually go down across development.

02:11:30.220 | I find this really interesting.

02:11:31.520 | What this means is that endogenous cannabinoids

02:11:34.060 | and activation of the CB1 and CB2 receptors

02:11:37.040 | are an integral part of neural development.

02:11:40.320 | And this is going to become especially relevant

02:11:42.200 | in considering whether or not pregnant mothers

02:11:44.080 | should or should not use cannabis or CBD.

02:11:48.180 | And it also points to some very interesting biology

02:11:51.240 | in terms of how the brain develops

02:11:54.280 | and how the body develops.

02:11:55.640 | Now the development of the brain and nervous system and body

02:11:58.920 | is a fascinating and vast literature,

02:12:01.140 | certainly far too vast to cover in today's episode,

02:12:04.100 | especially at this late hour, as it were.

02:12:06.860 | But we will have a future episode

02:12:08.780 | all about brain development.

02:12:10.840 | In terms of the effects of cannabis,

02:12:13.720 | it's sufficient to say that cannabinoid receptors

02:12:17.340 | are present and active in the developing fetus.

02:12:21.160 | They are present and active in the newborn.

02:12:23.460 | They are present and active in adolescents.

02:12:26.000 | And across that time from conception until adolescence,

02:12:30.080 | endogenous cannabinoids are mainly responsible

02:12:32.820 | for the actions of those cannabinoid receptors.

02:12:35.940 | During that time, the cannabinoid receptors

02:12:37.900 | are having very specific effects

02:12:39.780 | that are distinct from their effects later in life.

02:12:42.320 | And those effects can largely be explained

02:12:44.160 | in terms of neural development.

02:12:45.500 | Again, we don't have time for an entire lecture on this now,

02:12:49.160 | but during development,

02:12:51.600 | your body was a collection of a bunch of cells.

02:12:54.280 | It's actually called a blastula,

02:12:55.920 | which means a ball of cells.

02:12:57.260 | And then those cells actually have to grow out connections

02:12:59.700 | and duplicate themselves.

02:13:01.380 | And this is a very interesting process

02:13:03.240 | by which neurons initially are situated far apart,

02:13:06.120 | and then they grow out connections

02:13:07.680 | and make contacts with one another.

02:13:09.000 | They remove certain connections

02:13:10.300 | depending on what kind of life events you're exposed to.

02:13:13.260 | If you have a wonderful event early in life

02:13:15.520 | or a traumatic early life,

02:13:17.480 | those connections change, et cetera.

02:13:19.340 | The important point for today's discussion

02:13:21.840 | is that the CB1 receptor in particular

02:13:25.080 | is expressed on every neuron in the developing brain

02:13:28.680 | and has been shown to be important

02:13:30.020 | for every aspect of neural development,

02:13:33.080 | from the proliferation of cells,

02:13:35.160 | meaning getting enough cells to create a brain,

02:13:37.500 | to the outgrowth of the so-called axons,

02:13:40.040 | the little wires that connect up neurons with one another,

02:13:43.220 | to the steering, the direction

02:13:45.720 | which those axons go in development, which is essential.

02:13:50.600 | And even so far as to explain the connections

02:13:54.200 | that form between neurons, the so-called synapses,

02:13:56.760 | and then how those synapses work.

02:13:58.660 | So the basic statement here is that endogenous cannabinoids

02:14:02.920 | and CB1 receptor activation are critical

02:14:05.080 | for every aspect of brain wiring and development.

02:14:08.040 | With that in mind,

02:14:10.120 | the statement I'm about to make is absolutely terrifying,

02:14:13.320 | at least to me,

02:14:14.160 | and frankly, it should be terrifying to you as well.

02:14:17.000 | And the statement is the current statistics

02:14:21.720 | on cannabis use in pregnant mothers is absolutely shocking.

02:14:26.720 | The most recent survey of pregnant mothers

02:14:30.080 | in the United States show that 15%, one five,

02:14:33.720 | 15% of pregnant mothers report using cannabis

02:14:37.620 | in some form or another,

02:14:39.200 | either smoking it or more likely ingestion of an edible,

02:14:43.840 | because they are aware of the negative effects of smoking

02:14:46.160 | on the developing fetus,

02:14:47.180 | ingestion of an edible to increase THC and/or CBD

02:14:52.100 | during pregnancy.

02:14:53.540 | Which to me, I have to say,

02:14:55.340 | as a developmental neurobiologist is, frankly, it's scary.

02:15:00.340 | It's absolutely scary because that CB1 receptor

02:15:03.540 | is not just a minor player in neural development,

02:15:06.340 | it is absolutely central to every critical aspect

02:15:09.440 | of brain wiring and development.

02:15:11.500 | Now, the long-term implications

02:15:12.940 | or even the short-term implications of this 15%

02:15:15.740 | of mothers self-reporting the use of cannabis

02:15:18.880 | at some point during pregnancy are not yet known.

02:15:22.160 | This is, as we would say, an experiment that's ongoing,

02:15:25.700 | but I'd be remiss if I didn't point out these data

02:15:28.560 | and just implore you, please, please, please,

02:15:31.400 | if you are pregnant or considering getting pregnant,

02:15:33.300 | you're a cannabis user, whether or not you're using edibles,

02:15:35.440 | if you're a CBD user,

02:15:37.040 | please do whatever is necessary to not ingest cannabis

02:15:44.140 | or smoke cannabis or ingest CBD during pregnancy.

02:15:47.760 | Now, there may be certain clinical indications

02:15:50.080 | by which your physician and your OB-GYN

02:15:53.300 | and the pediatrician that will eventually be the pediatrician

02:15:56.340 | for your child will prescribe CBD,

02:16:00.700 | although it's hard to imagine what those are.

02:16:02.420 | I contacted a number of different pediatricians and OB-GYNs

02:16:07.340 | and not a single one said they would ever suggest

02:16:10.460 | and in fact would strongly discourage their patients

02:16:12.940 | from using cannabis during pregnancy.

02:16:15.980 | But I think that the advent of edible forms of cannabis

02:16:20.900 | and the combination of THC and CBD in certain products

02:16:25.820 | and the fact that most people view CBD as safer

02:16:28.780 | because it does not include as, or does not have,

02:16:32.100 | I should say, the psychoactive effects that THC does

02:16:35.180 | has led to a situation where you have 15%

02:16:39.580 | of pregnant mothers using cannabis

02:16:41.340 | at some point during pregnancy

02:16:43.100 | and maybe even frequently throughout pregnancy.

02:16:45.580 | And the effects on the developing fetus

02:16:47.280 | are completely unknown,

02:16:49.020 | but recall that cannabis and THC and CBD out-compete,

02:16:54.020 | meaning they park in the receptor

02:16:56.860 | for endogenous cannabinoids

02:16:58.600 | and prevent endogenous cannabinoids

02:17:01.160 | from having their normal level and pattern of action.

02:17:04.500 | So this is absolutely critical.

02:17:06.060 | I cannot encourage you enough, or rather I should say,

02:17:08.560 | I cannot discourage enough the use of cannabis

02:17:12.720 | and any related compounds in cannabis, edible or smoked,

02:17:17.500 | certainly not smoked, but even edible during pregnancy.

02:17:21.160 | And certainly in breastfeeding, lactating mothers,

02:17:25.420 | the same is also true.

02:17:26.400 | Recall that cannabis and THC and CBD

02:17:30.000 | are incredibly lipophilic.

02:17:32.300 | They are fat soluble and they get into cells very readily

02:17:35.800 | and they cross the blood brain barrier,

02:17:37.240 | they cross the blood placental barrier.

02:17:39.700 | So when I encountered this statistic,

02:17:41.540 | I had to kind of wipe my eyes a few times.

02:17:43.500 | I could not believe it.

02:17:44.700 | And yet I cross-checked that number

02:17:46.820 | with a few other studies.

02:17:47.920 | A few others have come in a little bit lower

02:17:49.740 | at somewhere like 13 to 14%,

02:17:51.940 | and a few have come in a little bit higher,

02:17:53.300 | but the average of 15% is both striking and shocking.

02:17:57.380 | So I don't know how to make the message more clear.

02:17:59.380 | I hope that is clear.

02:18:00.540 | Please do not use any cannabis, THC,

02:18:05.220 | or related things, including CBD, smoked or edible,

02:18:09.320 | if you're pregnant, lactating, et cetera.

02:18:12.860 | Now we are at the point where we need to consider

02:18:15.220 | some of the negative health effects of cannabis

02:18:17.120 | that have been well-documented in peer-reviewed studies.

02:18:19.620 | And before I do this,

02:18:20.900 | I want to return to a point that I made earlier,

02:18:22.660 | which is that nothing that I am about to say

02:18:25.380 | relates directly to issues of legality.

02:18:28.100 | If we consider alcohol, for instance,

02:18:30.460 | alcohol is legal in most areas of the world,

02:18:32.900 | it's certainly legal in the US,

02:18:34.780 | and yet there's an age limit for its use.

02:18:37.940 | Typically, it's not available to people

02:18:39.900 | until they're 21 or older.

02:18:41.660 | It's not to say that certain people don't use it

02:18:43.220 | before age 21, but it's not legal.

02:18:46.980 | It is illegal to buy or possess alcohol,

02:18:50.100 | consume alcohol before age 21.

02:18:52.180 | And I think with good reason,

02:18:53.420 | because the brain is still developing.

02:18:55.980 | Likewise, we can have a informed discussion about cannabis

02:19:01.700 | and its various components that can fully acknowledge

02:19:05.300 | the reality, which is that one of the major harms of cannabis

02:19:10.300 | in the past has been the legal ramifications

02:19:13.780 | of cannabis being illegal.

02:19:15.260 | That's a statement that is no longer controversial.

02:19:18.980 | And this is not a discussion about legalization

02:19:21.000 | or non-legalization.

02:19:22.260 | If you look to the scientific literature,

02:19:24.240 | the epidemiological literature,

02:19:26.720 | there are wonderful data out of Carleton University

02:19:29.320 | and elsewhere in Canada,

02:19:30.960 | showing that many of the negative effects of marijuana

02:19:35.960 | and THC are due to the criminal justice system itself.

02:19:41.100 | That is the creation of illicit drug businesses,

02:19:45.600 | the creation of organized crime,

02:19:47.780 | the creation of a number of different features

02:19:50.200 | related to the illegality of cannabis.

02:19:54.220 | And again, this isn't the topic of today's episode,

02:19:57.280 | but that should be acknowledged.

02:19:59.240 | And at the same time, we need to acknowledge

02:20:01.340 | that when a compound, a drug

02:20:04.540 | or whatever you want to call it becomes legal,

02:20:07.580 | there's a tendency to assume that it's safe

02:20:09.620 | and safe for everybody.

02:20:11.220 | And with respect to cannabis and THC and perhaps even CBD,

02:20:15.820 | but certainly for THC and cannabis that's smoked or vaped

02:20:20.800 | or consumed in edible form, that is simply not the case.

02:20:24.740 | There are clear data pointing to negative health effects

02:20:28.420 | of cannabis use and THC use,

02:20:30.440 | which again is not to say that there are not

02:20:32.480 | positive effects on mood, anxiety, pain relief, et cetera.

02:20:36.000 | Those are out there and they exist.

02:20:37.520 | And we will mention some of those, of course.

02:20:39.200 | And we've talked about some of those,

02:20:40.780 | creativity, for instance, et cetera.

02:20:42.900 | But if we do not acknowledge the negative health effects

02:20:46.280 | that are documented in the literature,

02:20:48.300 | then we are overlooking some very important data,

02:20:51.540 | especially as it relates to the development of psychosis

02:20:54.960 | in certain individuals.

02:20:56.940 | So with that said, there are very strong data,

02:21:01.180 | and I will provide links to these resources,

02:21:03.260 | pointing to the fact that for people

02:21:04.820 | who are chronic users of cannabis,

02:21:07.180 | that is using it twice a week or more,

02:21:09.720 | that over time their levels of anxiety actually increase.

02:21:13.540 | And this is true even for individuals

02:21:15.580 | that are using strains of cannabis

02:21:17.180 | that while under the influence of cannabis reduce anxiety.

02:21:21.460 | Over time, meaning over the course of 12 or more months,

02:21:26.500 | there is a well-documented effect of the anxiety relief

02:21:31.500 | that cannabis and THC initially brought

02:21:35.220 | being less and less potent.

02:21:36.860 | That is people need to smoke more of it or ingest more THC

02:21:41.340 | in order to achieve the same level of anxiety relief.

02:21:44.420 | And in some cases, a switch from anxiety relief

02:21:47.980 | to increase in anxiety.

02:21:50.080 | And again, that's increase in anxiety,

02:21:52.420 | not just when the drug is not being consumed,

02:21:55.860 | but also while under the influence of the drug.

02:21:58.580 | Why would that be?

02:21:59.900 | We have to go back to our understanding

02:22:01.740 | of the CB1 receptor and the potency

02:22:04.980 | with which THC binds to that CB1 receptor.

02:22:08.200 | When THC is brought into the system over and over again,

02:22:12.660 | meaning twice a week or more,

02:22:16.000 | the binding of THC to that CB1 receptor

02:22:19.320 | eventually causes a sort of habituation or attenuation

02:22:23.480 | of the entire process of binding the receptor

02:22:26.740 | and creating the psychoactive effects.

02:22:28.680 | So initially it creates anxiety relief,

02:22:30.720 | but over time, the affinity for the receptor doesn't change,

02:22:35.080 | meaning it can still park in that slot

02:22:36.600 | with a lot of affinity, a lot of strength,

02:22:39.360 | but there are fewer receptors available.

02:22:43.120 | And then the signaling that's downstream of those receptors

02:22:46.540 | becomes less and less robust.

02:22:48.720 | Now, this is a topic we didn't get into

02:22:50.800 | in too much detail today

02:22:52.380 | because I didn't want to include

02:22:53.540 | even more biological detail,

02:22:55.220 | but the CB1 receptor is a so-called

02:22:57.980 | G protein-coupled receptor.

02:23:00.180 | That's a mouthful, but a G protein-coupled receptor

02:23:02.660 | basically is like a bucket brigade.

02:23:04.800 | So while some receptors in the brain and body

02:23:06.620 | are such that when something, a chemical binds to them,

02:23:09.940 | that receptor has a direct action,

02:23:11.660 | like it opens and allows stuff to rush into the cell,

02:23:14.060 | increases the excitability of the cell,

02:23:16.280 | so-called fast effects.

02:23:18.000 | These G protein-coupled receptors,

02:23:20.360 | and CB1 is a G protein-coupled receptor,

02:23:23.560 | they are more like a bucket brigade

02:23:25.020 | where they kick off a process through one molecule

02:23:28.320 | that then is handed off to another molecule

02:23:30.720 | that this then is handed off to another molecule.

02:23:32.820 | It's a long chain or cascade of events.

02:23:36.160 | Those long chains or cascades of events

02:23:38.660 | have a lot of opportunity for regulation, for adjustment.

02:23:42.400 | Receptor systems in the brain and body,

02:23:44.080 | especially receptor systems like the cannabinoid system

02:23:46.400 | that are used to being kind of tickled, not punched,

02:23:49.600 | tickled by endogenous cannabinoids every once in a while,

02:23:52.080 | some binds, has an effect,

02:23:53.940 | but certainly not bound with incredible potency

02:23:58.080 | and over and over again,

02:23:59.080 | as they are when THC is coming into the system.

02:24:01.540 | Well, those systems eventually over time,

02:24:03.140 | they adjust themselves so that the body and those cells

02:24:07.040 | can achieve so-called homeostasis.

02:24:09.360 | So when people are using THC more than twice a week,

02:24:13.740 | what ends up happening is those G protein-coupled receptors

02:24:16.240 | and the downstream signaling mechanisms

02:24:17.960 | start to adjust themselves

02:24:19.480 | and it requires more and more drug,

02:24:23.280 | so either higher dosages or more frequent use.

02:24:26.020 | And a lot of the positive effects,

02:24:29.380 | the so-called decrease in anxiety,

02:24:30.880 | increased focus, increased creativity,

02:24:32.660 | some of that starts to wane.

02:24:34.120 | It starts to dissipate

02:24:35.160 | and people wonder why they have to use so much cannabis

02:24:37.820 | just to achieve a fraction of the effect

02:24:40.440 | that they used to be able to achieve with even a lower dose.

02:24:44.520 | So anxiety is getting worse over time

02:24:46.660 | and that's anxiety during the drug use

02:24:49.240 | and outside of the drug use.

02:24:51.140 | Some people work around that or try to work around that

02:24:54.940 | by using varying strains of cannabis

02:24:57.920 | or changing the pattern of delivery from smoking to vaping

02:25:01.620 | or from vaping to edible and from edible to transdermal.

02:25:04.720 | Anyway, they go through a lot of gymnastics

02:25:06.720 | and writhing and seeking,

02:25:09.860 | but nonetheless, anxiety increases over time.

02:25:12.820 | Also, it's very clear that depression increases over time

02:25:17.440 | and especially, this is surprising to me,

02:25:19.600 | but especially for individuals that were not depressed

02:25:22.740 | at the outset of their use.

02:25:24.260 | In other words, they didn't start using cannabis

02:25:25.840 | because they were depressed,

02:25:27.480 | but rather the depression starts to emerge

02:25:30.660 | as a consequence of the cannabis and THC use.

02:25:34.300 | So that's serious.

02:25:35.220 | In fact, we now know,

02:25:37.760 | based on really solid epidemiological evidence,

02:25:40.200 | that depression is not a strong predictor

02:25:43.020 | of seeking out cannabis.

02:25:45.440 | It doesn't drive terribly many people

02:25:48.080 | to seek out cannabis use,

02:25:50.000 | but cannabis use itself makes people four times likelier

02:25:54.440 | to develop a chronic major depression.

02:25:57.600 | So anxiety is increasing, depression is increasing,

02:26:01.600 | and this turns out to be especially relevant

02:26:05.000 | and important to young people.

02:26:06.800 | Why do I say that?

02:26:07.720 | Well, if you look at the data,

02:26:09.360 | and again, I think some of the strongest data

02:26:11.480 | or data to come out of the Canadian system,

02:26:13.880 | they've done some really beautiful controlled studies.

02:26:15.920 | I really hope to invite some of the people

02:26:18.380 | who arranged and ran those studies

02:26:20.660 | as guests onto the Huberman Lab Podcast.

02:26:22.820 | But if you look at the data out of Canada

02:26:25.560 | or you look at some of the data

02:26:26.600 | out of Northern Europe and the US,

02:26:28.360 | what you find is that the probability

02:26:31.120 | that somebody will use cannabis

02:26:33.280 | and then go on to use it chronically

02:26:35.960 | correlates very strongly with age.

02:26:37.720 | So for instance, some of the highest degree of cannabis use

02:26:40.820 | is among individuals 16 to 24 years old.

02:26:44.820 | In fact, in individuals who are 16 to 24 years old,

02:26:48.380 | and in particular in students

02:26:50.720 | and people who are working, surprising,

02:26:53.260 | more than in unemployed populations,

02:26:56.180 | being young, 16 to 24, at least to me that's young,

02:26:59.580 | and being a student or working doubles the likelihood

02:27:03.660 | that somebody is going to use cannabis on a regular basis,

02:27:06.400 | twice or more per week.

02:27:08.580 | The typical age of initiating cannabis use nowadays

02:27:11.120 | is about 19 years old, so 18.7.

02:27:14.760 | And about 20% of people in that age bracket

02:27:18.400 | of 16 to 24 years old are using cannabis daily,

02:27:22.000 | either by vaping, by smoking, or by edible.

02:27:24.860 | That's an enormous number.

02:27:26.160 | At least by my read, it's an enormous number.

02:27:28.360 | And here's why it's of really serious concern.

02:27:30.660 | During the ages of 16 to 24,

02:27:35.860 | the cannabinoid receptors are still available.

02:27:38.780 | They are not being as strongly driven

02:27:40.760 | by endogenous cannabinoids.

02:27:42.620 | But by ingestion of THC and/or CBD,

02:27:47.620 | there are downstream effects on the signaling

02:27:50.040 | within those cells that all the data point

02:27:53.520 | to creating a much, much higher likelihood

02:27:58.340 | of developing major depression, severe anxiety,

02:28:02.160 | or psychosis at later ages.

02:28:04.640 | So to be very clear,

02:28:05.860 | cannabis use between the ages of 16 to 24

02:28:09.420 | in both males and females is increasing anxiety,

02:28:13.200 | increasing depression in the immediate years

02:28:15.580 | and within the one year's time or so,

02:28:17.440 | so much so that people are using cannabis ongoing

02:28:21.140 | in an attempt to reduce that anxiety

02:28:24.080 | and reduce that depression.

02:28:25.580 | But in addition to that, the cannabis use,

02:28:28.140 | and because of the signaling mechanisms involved,

02:28:31.340 | are predisposing those individuals to psychosis later in life.

02:28:35.600 | If you look at individuals who start using cannabis

02:28:38.920 | even younger, age 14, or even as young as 12,

02:28:43.660 | the probability of psychosis later in life,

02:28:46.040 | in particular schizophrenic or schizophrenic-like episodes,

02:28:49.680 | more than doubles.

02:28:51.380 | So this is of really serious concern.

02:28:54.220 | And this is completely aside

02:28:56.480 | from any so-called positive effects

02:28:58.660 | or beneficial effects of cannabis

02:29:01.300 | that people might derive from occasional use as adults,

02:29:03.980 | meaning people older than 25.

02:29:06.000 | So for the person who's older than 25

02:29:07.700 | who eats an edible every once in a while

02:29:09.980 | or who smokes cannabis every once in a while,

02:29:12.300 | and people love to make the argument,

02:29:14.060 | it's not as bad as alcohol,

02:29:15.780 | which frankly is a terrible argument

02:29:17.500 | because if you saw our episode on alcohol,

02:29:19.100 | alcohol is pretty bad.

02:29:20.860 | But even so, it's just not a good argument.

02:29:23.740 | Saying that something is good

02:29:25.140 | because it's not as bad as something else

02:29:27.020 | is simply just not a good or valid argument,

02:29:29.300 | at least not biologically speaking.

02:29:31.000 | The use of cannabis in young populations

02:29:35.220 | is very strongly predisposing people to psychotic episodes.

02:29:38.660 | And we know the mechanism by which this occurs.

02:29:42.700 | This occurs by a thinning of the so-called gray matter.

02:29:46.860 | And it's called gray matter

02:29:48.340 | because with neurons, nerve cells,

02:29:51.220 | they have a so-called cell body.

02:29:52.700 | That's the part that contains the DNA

02:29:54.660 | and manufactures all the neurotransmitters, et cetera.

02:29:57.100 | And those are shipped out to the other parts of the neuron

02:30:00.080 | that include the axon, the wires between axons.

02:30:02.460 | And those axons under the microscope,

02:30:05.100 | because they have a lot of fatty tissue around them,

02:30:06.980 | and this is healthy fatty tissue

02:30:08.260 | that allows electrical transmission to be fast,

02:30:10.340 | that fatty tissue, those portions of the cells

02:30:12.820 | are called white matter.

02:30:13.920 | So you have gray matter and white matter.

02:30:15.580 | Gray matter are the so-called cell bodies

02:30:17.340 | where the DNA and all this stuff is manufactured.

02:30:19.680 | White matter are the axons or the wires

02:30:23.660 | through which all the key components are shipped out

02:30:26.300 | to the synapse, et cetera.

02:30:27.740 | Wonderful data.

02:30:30.180 | And I do say wonderful

02:30:31.360 | because this is part of a large-scale consortium,

02:30:33.780 | and we will provide a link to the paper.

02:30:35.060 | This was published in Translational Psychiatry

02:30:37.700 | just this year.

02:30:38.880 | Point to the fact that adolescent cannabis use

02:30:43.480 | accelerates the thinning of the prefrontal cortex

02:30:46.580 | and the gray matter in particular.

02:30:47.900 | So what this means is while during normal development,

02:30:51.580 | the gray matter, the prefrontal cortex,

02:30:53.860 | and all the cells there are indeed intended,

02:30:56.240 | it's a normal process for it to thicken

02:30:58.420 | and then thin a little bit as connections are adjusted

02:31:02.540 | and people learn and mature and grow up.

02:31:04.620 | This is part of the normal healthy maturational process

02:31:07.180 | independent of cannabis use.

02:31:09.820 | When kids, 'cause these really are kids, use cannabis

02:31:13.820 | and it doesn't matter the mode of cannabis delivery,

02:31:15.860 | whether or not it's vaping or smoking or edible,

02:31:18.360 | that gray matter thins at a much, much greater rate.

02:31:21.560 | And the reason I like this paper

02:31:22.860 | published in Translational Psychiatry this year so much

02:31:26.380 | is that they link the amount of cannabis use,

02:31:29.520 | heavy, moderate, light, or no cannabis use

02:31:32.760 | to the rate of prefrontal cortical thinning.

02:31:35.480 | And it's absolutely clear from these data

02:31:38.500 | that the more often young people,

02:31:41.520 | meaning individuals between the age of 14 and 25,

02:31:44.720 | the more often they consume or smoke or vape cannabis,

02:31:48.800 | the faster and the more extreme that cortical thinning is.

02:31:52.220 | And the cortical thinning is occurring

02:31:53.620 | in exactly the area of the brain

02:31:55.060 | that's involved in planning,

02:31:56.740 | in control over one's emotions, in reflexes,

02:32:00.560 | in organizing one's life in a number of different ways,

02:32:03.980 | anywhere from cleaning one's room, literally,

02:32:06.660 | you know, knowing what goes where,

02:32:08.100 | to making plans that extend out through the day,

02:32:10.700 | through the week, through a year,

02:32:12.140 | essentially becoming a functional human being

02:32:14.060 | involves using your prefrontal cortex

02:32:15.980 | in a variety of different contexts

02:32:17.520 | and different sort of time domains,

02:32:19.320 | the time domain of an hour, the time domain of a day.

02:32:21.820 | Making plans and being able to execute plans

02:32:25.000 | is fundamental to being a healthy human being.

02:32:26.940 | And it's absolutely clear from these data

02:32:29.080 | that the more cannabis one uses,

02:32:32.780 | the more impaired those neural circuits are.

02:32:35.360 | There's simply no other way to view these data.

02:32:38.800 | In fact, so much so that even small amounts of cannabis use

02:32:42.420 | are associated with rates of cortical thinning

02:32:44.580 | and degrees of cortical thinning

02:32:45.980 | that are really detrimental and concerning

02:32:48.340 | for normal cognitive processes.

02:32:51.220 | If you were somebody who smoked marijuana

02:32:54.180 | or consumed cannabis in any form or another

02:32:57.140 | during adolescence,

02:32:59.100 | does that mean that your prefrontal cortex

02:33:00.980 | can never be rescued, that it can't come back?

02:33:03.780 | Well, the short answer is

02:33:05.260 | it probably can be rescued to some degree.

02:33:07.380 | It will depend on how much cannabis you were using

02:33:10.940 | and how often and what strains of cannabis, et cetera.

02:33:14.920 | There's really no traveling back in time.

02:33:16.620 | As my graduate advisor used to say,

02:33:18.460 | time machines are broken.

02:33:20.020 | At least for now, we don't have time machines.

02:33:21.480 | So all you can really do is try and emphasize,

02:33:24.700 | first of all, quitting cannabis in any form

02:33:28.540 | and focusing on behaviors that emphasize endothelial cell,

02:33:33.540 | blood flow, health to the brain.

02:33:35.700 | So that would be cardiovascular exercise,

02:33:38.740 | adequate nutrition, not smoking nicotine.

02:33:41.500 | And there are a number of other things that one can do.

02:33:43.860 | We will do an entire episode

02:33:45.020 | all about trying to reverse the effects of cannabis

02:33:48.940 | and other drug use during adolescence.

02:33:50.840 | We don't have time to do a deep dive on that right now.

02:33:52.940 | But all the things that standardize

02:33:54.580 | and kind of promote health, adequate sleep,

02:33:58.040 | good social connection, regular cardiovascular

02:34:01.540 | and weight training exercise, healthy nutrition,

02:34:04.660 | what that represents to you,

02:34:05.820 | healthy metabolic function and weight, et cetera,

02:34:08.060 | those are all going to facilitate

02:34:09.620 | some recovery of brain function

02:34:12.300 | in particular prefrontal cortical function

02:34:14.660 | by way of all the positive effects

02:34:16.100 | that those behaviors and choices have.

02:34:19.160 | But with that said, if you are in the age bracket

02:34:22.220 | that I've been referring to,

02:34:23.280 | this 14 to 25-year-old age bracket,

02:34:25.700 | and you are a occasional even or chronic cannabis user,

02:34:30.540 | you should be very, very careful and concerned

02:34:34.040 | about the long-term effects that could potentially have.

02:34:36.960 | That statement is bolstered by another statistic,

02:34:39.380 | which is that unlike a lot of other drugs,

02:34:42.820 | the rate of cannabis use is strongly related

02:34:47.600 | to how dangerous people perceive cannabis to be.

02:34:52.500 | And that might seem obvious on the one hand.

02:34:54.740 | If you think something is very, very dangerous,

02:34:57.260 | you would expect that the probability

02:34:58.840 | that somebody would use it would be very, very low.

02:35:01.000 | And if they think something is safe,

02:35:02.080 | the probability would be high.

02:35:04.500 | But that isn't necessarily the case.

02:35:06.600 | If you think about it, cannabis is a unique instance

02:35:10.500 | in which nowadays we are hearing,

02:35:12.900 | yes, it's becoming legal in a number of areas,

02:35:15.380 | and we talked earlier about why that's probably a good thing

02:35:17.600 | in most circumstances,

02:35:19.260 | but that we aren't just hearing that cannabis is safe

02:35:22.340 | or it's not just being implied that cannabis is safer,

02:35:25.960 | but many more people are talking

02:35:28.100 | about the positive effects of cannabis

02:35:30.820 | without a lot of discussion

02:35:32.340 | about the negative effects of cannabis.

02:35:34.340 | And I realize that saying this is going to upset

02:35:36.600 | some people out there,

02:35:37.440 | because I know that there are a number of people

02:35:38.760 | who fought very hard for the legalization process,

02:35:41.080 | and I want to acknowledge that.

02:35:42.880 | I also want to acknowledge the many known positive effects

02:35:47.720 | of cannabis in adults with very occasional use,

02:35:52.520 | provided it is delivered safely

02:35:55.280 | and in the safe context and setting and with legality.

02:35:59.520 | That is entirely distinct from the issue

02:36:02.020 | of whether or not cannabis is safe for the developing brain

02:36:04.840 | and body.

02:36:05.680 | Again, I'm not demonizing anybody for using cannabis,

02:36:09.060 | but I want to make the point very simply and very directly.

02:36:12.760 | It is far and away a different circumstance for the brain

02:36:17.200 | for an individual to be 25 years or older

02:36:21.920 | and using cannabis in whatever form occasionally,

02:36:25.960 | or maybe even frequently,

02:36:27.720 | than it is for a young person aged 14 to 25

02:36:32.720 | to be using cannabis, either by smoking or vaping

02:36:36.620 | or by edible or any other form on the brain and body.

02:36:41.240 | It's absolutely clear that the brain continues to develop

02:36:44.260 | at least until age 25 and that a huge number of systems

02:36:47.980 | related to mood regulation, so-called executive function,

02:36:51.300 | the ability to organize one's thoughts,

02:36:53.040 | plan and execute plans,

02:36:55.500 | essentially to become a functional human being.

02:36:58.060 | That's one portion of becoming a functional human being,

02:37:00.500 | but certainly an essential one.

02:37:02.620 | All of that relies on the fine tuning

02:37:05.000 | of this neural circuitry that we've been talking about

02:37:07.980 | up until now.

02:37:09.660 | And it's abundantly clear that cannabis and THC in particular

02:37:14.660 | dramatically disrupt those processes.

02:37:19.340 | So if this isn't clear enough just from my statements,

02:37:23.940 | I'd like to point to a particular paper.

02:37:26.000 | This is one of the more impactful papers

02:37:27.620 | in this area in recent years.

02:37:29.640 | This is a paper published in Lancet Psychiatry in 2022.

02:37:33.660 | Title is Association of Cannabis Potency

02:37:36.700 | with Mental Ill Health and Addiction, a Systematic Review.

02:37:40.300 | There are a number of very important points

02:37:41.940 | in this very fine paper.

02:37:43.780 | Lancet Psychiatry is one of the premier medical journals

02:37:46.980 | out there and they evaluated a huge number of studies.

02:37:51.420 | They actually looked at more than 4,000 studies.

02:37:54.420 | They selected the ones that were only the most rigorous

02:37:57.540 | in terms of study design and analysis

02:38:00.460 | and rigor of conclusions.

02:38:02.620 | And they looked at how early use of cannabis

02:38:06.420 | impacted later probability of development of psychosis

02:38:10.860 | and other psychiatric conditions.

02:38:12.940 | And the takeaways from this study are very clear.

02:38:16.580 | First of all, chronic cannabis use,

02:38:19.820 | so more than twice per week, has consistently been associated

02:38:22.980 | with mental health disorders.

02:38:24.320 | I'm pulling some phrases directly from the paper.

02:38:26.940 | Heavy cannabis use, meaning cannabis use more frequent

02:38:31.160 | than twice per week has been associated

02:38:34.340 | with four times the risk of psychosis later in life.

02:38:37.180 | In particular, schizophrenia and bipolar-like episodes.

02:38:40.700 | Now we've done an episode on bipolar disorder,

02:38:43.020 | so-called bipolar depression.

02:38:44.660 | We have not yet done one on schizophrenia,

02:38:46.220 | but both bipolar disorder and schizophrenia

02:38:48.780 | have a very, very strong genetic component.

02:38:51.860 | There's a 30, three zero, 30 times greater likelihood

02:38:55.340 | that you'll have bipolar disorder

02:38:56.560 | if you have a first relative who has bipolar disorder.

02:38:59.420 | And then it's also the case that using cannabis,

02:39:03.000 | especially during adolescence and the teen years

02:39:05.760 | and up until age 25, create a four times greater risk

02:39:09.300 | of psychosis for those that have a predisposition

02:39:12.540 | to bipolar disorder and/or schizophrenia.

02:39:15.860 | Now I don't hear very much about this in the media.

02:39:18.680 | This paper got some attention

02:39:20.060 | and then it sort of got swept away.

02:39:22.780 | I don't think that was an intentional sweeping way.

02:39:24.460 | There's just a lot of events in the world, as you well know.

02:39:27.780 | But I think it's a particularly important set of findings

02:39:31.160 | because obviously in looking at so many studies,

02:39:34.940 | it distills out the strongest findings that are out there

02:39:37.300 | and really pulls the consistent messages

02:39:40.580 | that are arriving from all these different studies.

02:39:42.700 | And as they point out, and again, I'm paraphrasing here,

02:39:45.980 | this is the first systematic review

02:39:47.580 | of the Association of Cannabis Potency.

02:39:50.820 | And all of the data point to a very clear conclusion,

02:39:53.300 | which is the more potent the THC concentration,

02:39:58.300 | the higher probability of developing psychosis

02:40:00.660 | or a major depressive episode

02:40:02.180 | or a major anxiety disorder later in life.

02:40:04.620 | That should be of particular concern

02:40:06.960 | because we know, we are absolutely clear about the fact

02:40:11.280 | that with the advent of all these new strains of cannabis

02:40:14.860 | and with the engineering and availability of cannabis

02:40:19.520 | at much higher potency, meaning THC potency,

02:40:24.060 | the risk of psychosis is going up and up

02:40:26.960 | and is likely to continue going up

02:40:28.500 | unless something is done to reduce

02:40:31.100 | the frequency of cannabis use to zero, ideally,

02:40:36.100 | or to very low frequency, very low potency

02:40:39.180 | in adolescents and teens and people aged 25 or younger.

02:40:43.620 | I know a lot of people don't want to hear this message

02:40:45.880 | because first of all, it's alarming.

02:40:47.200 | And second of all, as I mentioned earlier,

02:40:49.800 | the statistics tell us that the greatest number of people

02:40:53.140 | that are starting to use cannabis

02:40:54.500 | are in the age bracket of 16 to 24.

02:40:57.240 | Many of them are functional in other areas of life.

02:41:00.360 | They are students, they are employed, et cetera.

02:41:03.740 | But when you couple that with the fact

02:41:05.820 | that the most frequent adopters of cannabis use

02:41:08.560 | are in this age bracket of 16 to 24,

02:41:11.280 | they're twice as likely to use as other individuals

02:41:14.640 | or to start using cannabis as our other individuals,

02:41:17.480 | plus the general perception out there

02:41:19.520 | because of the way that cannabis is discussed in the media

02:41:22.600 | and by sports figures and by celebrities

02:41:24.760 | and by politicians, et cetera,

02:41:27.240 | that it's not as bad as alcohol and maybe not that bad

02:41:30.920 | and maybe even has health benefits,

02:41:33.580 | then you're essentially setting up a system

02:41:35.000 | where young people are far more likely

02:41:37.040 | to adopt and continue cannabis use

02:41:39.680 | without realizing these serious health consequences

02:41:42.660 | that await them later.

02:41:43.760 | With all of that said, I of course, again,

02:41:48.120 | want to acknowledge that there have been

02:41:51.480 | well-demonstrated effects of cannabis for reducing pain,

02:41:56.480 | in particular in chemotherapy

02:41:58.920 | and in the context of reducing nausea

02:42:02.240 | in people suffering from cancer or chemotherapy.

02:42:04.800 | There is a well-known effect

02:42:07.460 | that one can generally point to as positive

02:42:09.960 | using cannabis for things like glaucoma,

02:42:13.400 | for lowering intraocular pressure

02:42:15.680 | and offsetting the loss of neurons

02:42:17.200 | that would lead to blindness,

02:42:18.220 | although there are other tools, of course,

02:42:19.640 | that don't involve cannabis use

02:42:21.240 | that can accomplish that as well,

02:42:23.560 | so-called intraocular pressure lowering drugs or drops.

02:42:28.440 | There is a list of probably a dozen or more

02:42:32.280 | psychological and bodily ailments

02:42:35.900 | that can be aided by cannabis use,

02:42:37.760 | in particular edible cannabis use of particular strains.

02:42:41.200 | Of course, I'm going to address each and every one of those

02:42:45.760 | in episodes where I'm talking, for instance,

02:42:48.200 | about eye disease or about chronic pain.

02:42:51.040 | I am in no way, shape, or form trying to rob

02:42:54.200 | the incredible efforts of the laboratories

02:42:56.540 | and people that have worked very hard

02:42:58.660 | to study and establish the valid uses of cannabis

02:43:02.680 | for treating various ailments

02:43:04.320 | and that continue to study cannabis

02:43:06.260 | in order to try and ameliorate the symptoms

02:43:08.860 | of different ailments.

02:43:10.000 | But today I really wanted to emphasize

02:43:12.780 | the biology of cannabis.

02:43:14.960 | Some of the often discussed effects,

02:43:18.160 | I guess one could call them positive effects,

02:43:19.660 | things like enhanced creativity,

02:43:20.940 | and really point to the nuance and actually the divergence

02:43:23.960 | of people who take cannabis and some experience

02:43:27.440 | heightened levels of creativity and some do not.

02:43:29.520 | Some people experience heightened levels of sexual arousal

02:43:33.500 | and some people experience the exact opposite

02:43:36.360 | and so on and so forth,

02:43:37.840 | rather than focus on all the potential positive

02:43:40.640 | and sort of emerging positive data about cannabis

02:43:44.040 | in different medical contexts.

02:43:45.740 | And at the same time, I strongly feel that it's important

02:43:48.480 | to acknowledge the shocking,

02:43:51.800 | because there's really no other way to describe it,

02:43:54.300 | the shocking effects of cannabis use

02:43:57.760 | on the developing fetus and the fact that so many pregnant

02:44:01.040 | and lactating mothers are using cannabis.

02:44:03.220 | I mean, that number 15% still has me dizzy

02:44:06.440 | with kind of disbelief and yet we need to acknowledge this

02:44:08.800 | and address this immediately.

02:44:11.360 | And I think it's vital to understand that cannabis use

02:44:15.300 | through any delivery mechanism,

02:44:18.960 | smoking or vaping or edible or otherwise,

02:44:22.120 | is very, very concerning.

02:44:24.680 | In fact, dangerous to the developing brain,

02:44:26.840 | certainly for the fetal brain and for the baby brain,

02:44:29.580 | but also for the adolescent brain

02:44:32.600 | and for the teen and young adult brain,

02:44:35.580 | not just because of the effects that it can have

02:44:37.440 | in the immediate term,

02:44:38.280 | those slow creeping increases in anxiety and depression

02:44:41.420 | brought on by cannabis use,

02:44:43.740 | but also the time release, if you will,

02:44:47.900 | on the development of psychosis

02:44:49.900 | and other types of major psychiatric disorders later in life.

02:44:54.240 | I acknowledge we've covered a lot of ground today

02:44:56.440 | and yet there's still far more ground

02:44:58.180 | that we could have covered

02:44:59.120 | and that we will indeed cover in future episodes.

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02:47:00.460 | without having to sign up for anything

02:47:01.820 | and decide whether or not you want to sign up.

02:47:03.480 | Again, that's the Neural Network newsletter

02:47:05.060 | at Hubermanlab.com.

02:47:06.820 | If you're not already following us on social media,

02:47:08.900 | we are Huberman Lab on Instagram, on Twitter,

02:47:11.340 | on Facebook, and on LinkedIn.

02:47:13.100 | And especially on Instagram and on Twitter,

02:47:16.020 | I cover many of the tools that are discussed

02:47:18.300 | on the Huberman Lab podcast,

02:47:19.340 | but also a lot of science and science-based tools

02:47:21.160 | not covered on the Huberman Lab podcast.

02:47:23.340 | Again, it's Huberman Lab on all platforms.

02:47:25.620 | So once again, thank you for joining me

02:47:27.100 | for today's discussion all about cannabis.

02:47:29.880 | And as always, thank you for your interest in science.

02:47:33.020 | [upbeat music]

02:47:35.600 | (upbeat music)

The Effects of Cannabis (Marijuana) on the Brain & Body | Huberman Lab Podcast #92

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